Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

Phase 2

Active, not recruiting

Conditions: Grade 2 Follicular Lymphoma
Grade 3a Follicular Lymphoma
Recurrent Follicular Lymphoma
Grade 1 Follicular Lymphoma
Refractory Follicular Lymphoma

Interventions: Procedure: Biopsy
Drug: Bendamustine Hydrochloride
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Procedure: Echocardiography
Procedure: Multigated Acquisition Scan
Drug: Lenalidomide
Drug: Cyclophosphamide
Biological: Obinutuzumab
Drug: Doxorubicin Hydrochloride
Procedure: Positron Emission Tomography
Drug: Umbralisib
Drug: Prednisone
Drug: Vincristine Sulfate

Registration Number: NCT03269669

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

Detailed Description: PRIMARY OBJECTIVE:

I. To compare the complete response rate up to 6 cycles after randomization as defined by centrally read positron emission tomography (PET)/computed tomography (CT) (integral biomarker) of 2 targeted therapeutic regimens (obinutuzumab + umbralisib \[TGR-1202\] or obinutuzumab + lenalidomide) with obinutuzumab + chemotherapy (cyclophosphamide, doxorubicin hydrochloride \[doxorubicin\], vincristine sulfate \[vincristine\], and prednisone \[CHOP\] or bendamustine hydrochloride \[bendamustine\]) in patients with early relapsing or refractory follicular lymphoma.

SECONDARY OBJECTIVES:

I. To validate the prognostic association of the m7-FLIPI model, demonstrating that the population of follicular lymphoma patients who respond poorly to chemoimmunotherapy are enriched for having a high-risk m7-FLIPI score, and that the score is associated with progression-free survival (integrated biomarker). (Primary translational medicine) II. To estimate the 30-month sustained complete response rate (CR30) defined by centrally read PET/CT with each of the regimens in this early relapsing or refractory follicular lymphoma population.

III. To estimate best response up to 12 cycles of therapy, progression free survival, duration of response and overall survival with each of the combinations in early relapsing or refractory follicular lymphoma.

IV. To evaluate the adverse effects of each of the regimens in early relapsing or refractory follicular lymphoma.

V. To evaluate the predictive performance of non-invasive genotyping (m7-FLIPI in circulating tumor deoxyribonucleic acid \[DNA\]) of plasma at study entry relative to standard tumor genotyping (m7-FLIPI) of formalin-fixed paraffin-embedded tumor tissue.

VI. To evaluate the association between the detection of active lymphoma by PET-CT and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I (CLOSED TO ACCRUAL): Patients receive obinutuzumab intravenously (IV) on day 1 and umbralisib orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM III:

PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity.

Patients in all arms undergo biopsy and echocardiogram (ECHO) or multigated acquisition scan (MUGA) during screening, and PET/CT scans and collection of blood throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 95

Inclusion Criteria

Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on PET/CT; patients that have involvement with large cell lymphoma are not eligible
Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration
Patients must have bone marrow biopsy performed within 42 days prior to registration
Patients must have an indication for therapy as determined by the treating investigator
All disease must be assessed and documented on the S1608 FDG-PET/CT assessment form
The intent is to enroll patients with follicular lymphoma (FL) relapsed within 2 years of completing their first course of chemotherapy (CHOP or bendamustine based therapy) + anti-CD20 therapy. Patient is still eligible if he/she received radiation therapy or anti-CD20 therapy prior to chemoimmunotherapy or if maintenance anti-CD20 therapy was administered after chemoimmunotherapy
- Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing CHOP or bendamustine-containing chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from the last dose of CHOP or bendamustine; relapsed patients must not have received any intervening chemotherapy
- Patients must have received only 1 course of chemotherapy, containing at least 3 cycles of CHOP or bendamustine; (note that no minimum dose of bendamustine is required)
- Patients who received any anti-CD20 antibody therapy prior to CHOP or bendamustine are eligible
- Patients who additionally received any maintenance anti-CD-20 antibody therapy or consolidative radioimmunotherapy within 2 years of the last dose of the CHOP or bendamustine therapy are eligible
- Involved field or involved site radiation is not considered a line of therapy; examples of eligible prior treatment regimens (note this list is not all inclusive):
  - 1st line rituximab treatment followed years later by bendamustine rituximab
  - Bendamustine rituximab x 4 cycles
  - 1st line rituximab treatment, 2nd line ibritumomab tiuxetan, followed by bendamustine bortezomib rituximab x 6 cycles followed by rituximab maintenance
  - Bendamustine obinutuzumab x 3 cycles
  - CHOP rituximab x 6 cycles followed by rituximab maintenance
For all forms of systemic therapy, patients must have completed therapy at least 21 days prior to registration; patients must have completed any radioimmunotherapy at least 84 days prior to registration; patients prior treatment related toxicities (except alopecia) must have resolved to grade 1 or less prior to registration
Patients must have tissue specimens collected prior to registration; patients must be offered participation in biobanking of residual specimens; with patient consent, residuals from the mandatory submission(s) will be banked for future research
Patients must be >= 18 years of age
All patients must have a Zubrod performance status of 0, 1 or 2
Absolute neutrophil count (ANC) >= 1,500/mcL within 28 days prior to registration
Platelets >= 75,000/mcL within 28 days prior to registration
Patients must have adequate renal function as documented by a calculated creatinine clearance >= 60 mL/min, within 28 days prior to registration
Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (=< 5 x IULN if secondary to lymphoma, Gilbert's syndrome, or medication related [e.g., indinavir, tenofovir, atazanavir]) within 28 days prior to registration
Direct bilirubin =< 1.5 x IULN (=< 5 x IULN if secondary to lymphoma) within 28 days prior to registration
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (=< 5 x IULN secondary to lymphoma) within 28 days prior to registration
Patients must have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 42 days prior to registration with a cardiac ejection fraction >= 45%
Patients with hepatitis B virus infection must have undetectable hepatitis B virus (HBV) on suppressive therapy and no evidence of HBV-related hepatic damage; patients with hepatitis C virus infection are eligible if complete eradication therapy has been successfully completed, and there is no detectable hepatitis C virus (HVC) or related hepatic damage; patients with known human immunodeficiency virus (HIV) infection are eligible if they meet all of the following criteria in addition to the other protocol eligibility criteria:
- Patient must have no history of acquired immune deficiency syndrome (AIDS)-related complications, other than a history of low CD4+ T-cell count (< 200/mm^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to leukemia and should not be used as an exclusion criterion if low
- Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the leukemia
- Patient must have serum HIV viral load of < 200 copies/mm^3
- Patient must be on combination antiretroviral therapy with minimal pharmacokinetic interactions with study therapy and minimal overlapping clinical toxicity with protocol therapy; (recommend a regimen of the integrase inhibitor dolutegravir combined with either disoproxil fumarate/emtricitabine or dolutegravir combined with tenofovir alafenamide/emtricitabine)
- Protease inhibitors and once daily formulations containing cobicistat are NOT allowed due to potential pharmacokinetic interactions with leukemia therapy
- Stavudine and zidovudine (AZT) are NOT allowed because of overlapping toxicity with protocol therapy
Patients must be able and willing to receive prophylaxis with daily aspirin, low molecular weight heparin, factor X inhibitors or warfarin if randomized to lenalidomide; patients unable or unwilling to take any listed prophylaxis are NOT eligible
No second prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for three years
Patients must have a complete history and physical examination within 28 days prior to registration
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to complete abstinence (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence [e.g., calendar, ovulation, symptothermal or post ovulation methods] and withdrawal are not acceptable methods of contraception) from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; while taking lenalidomide, during dose interruptions, and for at least 28 days after the last dose of lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a female who: 1) has achieved menarche at some point; 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; NOTE: patients not randomized to receive lenalidomide will not be required to undergo serial pregnancy testing or lenalidomide counseling after registration
Patients must have lactate dehydrogenase (LDH) and beta-2-microglobulin collected within 28 days prior to registration
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Exclusion Criteria

Patients must not have clinical evidence of central nervous system involvement by lymphoma since the proposed treatment strategies are not designed to address central nervous system (CNS) involvement adequately; if performed, any laboratory or radiographic tests performed to assess CNS involvement must be negative
Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (obinutuzumab, lenalidomide)	Biopsy	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Biopsy	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Biospecimen Collection	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Computed Tomography	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Echocardiography	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Multigated Acquisition Scan	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Positron Emission Tomography	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Biospecimen Collection	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Computed Tomography	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Echocardiography	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Multigated Acquisition Scan	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Positron Emission Tomography	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Biopsy	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Biospecimen Collection	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Computed Tomography	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Echocardiography	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Multigated Acquisition Scan	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Positron Emission Tomography	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Vincristine Sulfate	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Obinutuzumab	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm I (obinutuzumab, umbralisib)	Umbralisib	CLOSED TO ACCRUAL: Patients receive obinutuzumab IV on day 1 and umbralisib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Lenalidomide	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm II (obinutuzumab, lenalidomide)	Obinutuzumab	Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Bendamustine Hydrochloride	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Doxorubicin Hydrochloride	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Cyclophosphamide	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Prednisone	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.
Arm III (obinutuzumab, combination chemotherapy)	Obinutuzumab	PRIOR BENDAMUSTINE-BASED CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. PRIOR CHOP CHEMOTHERAPY: Patients receive obinutuzumab IV on day 1, and bendamustine IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 or 12 cycles (bendamustine and obinutuzumab, respectively) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and ECHO or MUGA during screening, and PET/CT scans and collection of blood throughout the trial.

Primary Outcome Measures

Name	Time	Method
Complete response (CR)	Up to 6 cycles

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 5 years	Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 31 eligible patients in each arm, OS at a particular time point, and the 30-month sustained response rate can be estimated to within at least +/- 18% with 95% confidence.
Sustained complete response rate (CR30)	Up to 30 months	Defined by centrally read positron emission tomography (PET)/computed tomography (CT).
Progression-free survival (PFS)	From date of registration to date of first observation of progressive disease, or death due to any cause, assessed up to 5 years	Will be calculated using the method of Kaplan-Meier. 95% confidence for the survival estimates will be constructed using the method of Brookmeyer-Crowley. With 31 eligible patients in each arm, progression free survival at a particular time point, and the 30-month sustained response rate can be estimated to within at least +/- 18% with 95% confidence.
Incidence of adverse events	Up to 5 years	Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (version 5.0 will be utilized for serious adverse events reporting only). Toxicity rates can be estimated to within at least +/- 18% with 95% confidence.
Duration of response (CR, partial response [PR])	From date of first documentation of response to treatment (CR, PR) to date of first documentation of progression, or death due to any cause, assessed up to 5 years	Will be calculated using the method of Kaplan-Meier.
Non-invasive genotyping and circulating tumor deoxyribonucleic acid (DNA) assessment	Up to 5 years	Sensitivity, specificity, positive predictive value, negative predictive value, and kappa coefficient will be used to evaluate the concordance. Will evaluate the association of detection of active lymphoma by positron emission tomography-computed tomography and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy. Chi-square test will be used to evaluate the association and odds ratio will be calculated
Active lymphoma and circulating tumor DNA in plasma	From baseline up to 30 months after initiation of treatment	The Cox proportional hazards model will be used to assess the association and odds ratio will be calculated.
m7-FLIPI model validation	Up to 5 years	The Cox proportional hazards model will be used to assess the association of the m7-FLIPI with to PFS.

Trial Locations

Locations (433): Longmont United Hospital
🇺🇸
Longmont, Colorado, United States
Rocky Mountain Cancer Centers-Longmont
🇺🇸
Longmont, Colorado, United States
Banner McKee Medical Center
🇺🇸
Loveland, Colorado, United States
Parker Adventist Hospital
🇺🇸
Parker, Colorado, United States
Rocky Mountain Cancer Centers-Parker
🇺🇸
Parker, Colorado, United States
The Carle Foundation Hospital
🇺🇸
Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
Parkview Hospital Randallia
🇺🇸
Fort Wayne, Indiana, United States
Parkview Regional Medical Center
🇺🇸
Fort Wayne, Indiana, United States
Reid Health
🇺🇸
Richmond, Indiana, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸
Clive, Iowa, United States
Mission Cancer and Blood - West Des Moines
🇺🇸
Clive, Iowa, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸
Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸
Grand Rapids, Michigan, United States
Macomb Hematology Oncology PC
🇺🇸
Warren, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸
West Bloomfield, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸
Ypsilanti, Michigan, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Central Care Cancer Center - Bolivar
🇺🇸
Bolivar, Missouri, United States
Saint Ann's Hospital
🇺🇸
Westerville, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Clackamas Radiation Oncology Center
🇺🇸
Clackamas, Oregon, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸
Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸
Coos Bay, Oregon, United States
Providence Newberg Medical Center
🇺🇸
Newberg, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸
Oregon City, Oregon, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States
Kaiser Permanente-Fremont
🇺🇸
Fremont, California, United States
Kaiser Permanente-Fresno
🇺🇸
Fresno, California, United States
Saint Joseph Hospital - Cancer Centers of Colorado
🇺🇸
Denver, Colorado, United States
Henry Ford Saint John Hospital - Van Elslander
🇺🇸
Grosse Pointe Woods, Michigan, United States
Henry Ford Rochester Hospital
🇺🇸
Rochester Hills, Michigan, United States
Alaska Breast Care and Surgery LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
Kaiser Permanente-Anaheim
🇺🇸
Anaheim, California, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸
Antioch, California, United States
PCR Oncology
🇺🇸
Arroyo Grande, California, United States
Sutter Auburn Faith Hospital
🇺🇸
Auburn, California, United States
Kaiser Permanente-Baldwin Park
🇺🇸
Baldwin Park, California, United States
Kaiser Permanente-Bellflower
🇺🇸
Bellflower, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸
Berkeley, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Kaiser Permanente Dublin
🇺🇸
Dublin, California, United States
Kaiser Permanente-Fontana
🇺🇸
Fontana, California, United States
Kaiser Permanente South Bay
🇺🇸
Harbor City, California, United States
City of Hope Seacliff
🇺🇸
Huntington Beach, California, United States
City of Hope at Irvine Lennar
🇺🇸
Irvine, California, United States
Kaiser Permanente-Irvine
🇺🇸
Irvine, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
City of Hope at Long Beach Elm
🇺🇸
Long Beach, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
Kaiser Permanente West Los Angeles
🇺🇸
Los Angeles, California, United States
Memorial Medical Center
🇺🇸
Modesto, California, United States
Kaiser Permanente-Modesto
🇺🇸
Modesto, California, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸
Mountain View, California, United States
Palo Alto Medical Foundation-Gynecologic Oncology
🇺🇸
Mountain View, California, United States
City of Hope Newport Beach
🇺🇸
Newport Beach, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸
Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-Ontario
🇺🇸
Ontario, California, United States
Palo Alto Medical Foundation Health Care
🇺🇸
Palo Alto, California, United States
VA Palo Alto Health Care System
🇺🇸
Palo Alto, California, United States
Kaiser Permanente - Panorama City
🇺🇸
Panorama City, California, United States
Eisenhower Medical Center
🇺🇸
Rancho Mirage, California, United States
Kaiser Permanente-Richmond
🇺🇸
Richmond, California, United States
Kaiser Permanente-Roseville
🇺🇸
Roseville, California, United States
Kaiser Permanente Downtown Commons
🇺🇸
Sacramento, California, United States
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
Kaiser Permanente-South Sacramento
🇺🇸
Sacramento, California, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸
Sacramento, California, United States
Kaiser Permanente-San Diego Mission
🇺🇸
San Diego, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸
San Diego, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸
San Francisco, California, United States
Kaiser Permanente-San Francisco
🇺🇸
San Francisco, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸
San Jose, California, United States
Kaiser Permanente San Leandro
🇺🇸
San Leandro, California, United States
Kaiser Permanente-San Marcos
🇺🇸
San Marcos, California, United States
Kaiser Permanente-San Rafael
🇺🇸
San Rafael, California, United States
Kaiser San Rafael-Gallinas
🇺🇸
San Rafael, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸
Santa Clara, California, United States
Palo Alto Medical Foundation-Santa Cruz
🇺🇸
Santa Cruz, California, United States
Kaiser Permanente-Santa Rosa
🇺🇸
Santa Rosa, California, United States
Sutter Pacific Medical Foundation
🇺🇸
Santa Rosa, California, United States
City of Hope South Pasadena
🇺🇸
South Pasadena, California, United States
Kaiser Permanente-South San Francisco
🇺🇸
South San Francisco, California, United States
Kaiser Permanente-Stockton
🇺🇸
Stockton, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸
Sunnyvale, California, United States
City of Hope South Bay
🇺🇸
Torrance, California, United States
City of Hope Upland
🇺🇸
Upland, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸
Vacaville, California, United States
Kaiser Permanente-Vallejo
🇺🇸
Vallejo, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸
Walnut Creek, California, United States
Kaiser Permanente-Woodland Hills
🇺🇸
Woodland Hills, California, United States
Rocky Mountain Cancer Centers-Aurora
🇺🇸
Aurora, Colorado, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Rocky Mountain Cancer Centers-Boulder
🇺🇸
Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers-Penrose
🇺🇸
Colorado Springs, Colorado, United States
Denver Health Medical Center
🇺🇸
Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Rocky Mountain Cancer Centers-Midtown
🇺🇸
Denver, Colorado, United States
Rocky Mountain Cancer Centers-Rose
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
Mercy Medical Center
🇺🇸
Durango, Colorado, United States
Mountain Blue Cancer Care Center - Swedish
🇺🇸
Englewood, Colorado, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Mountain Blue Cancer Care Center
🇺🇸
Golden, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸
Grand Junction, Colorado, United States
Banner North Colorado Medical Center
🇺🇸
Greeley, Colorado, United States
Rocky Mountain Cancer Centers-Greenwood Village
🇺🇸
Greenwood Village, Colorado, United States
Rocky Mountain Cancer Centers-Lakewood
🇺🇸
Lakewood, Colorado, United States
Saint Anthony Hospital
🇺🇸
Lakewood, Colorado, United States
Rocky Mountain Cancer Centers-Littleton
🇺🇸
Littleton, Colorado, United States
Littleton Adventist Hospital
🇺🇸
Littleton, Colorado, United States
Rocky Mountain Cancer Centers-Sky Ridge
🇺🇸
Lone Tree, Colorado, United States
Sky Ridge Medical Center
🇺🇸
Lone Tree, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸
Pueblo, Colorado, United States
Rocky Mountain Cancer Centers-Thornton
🇺🇸
Thornton, Colorado, United States
Intermountain Health Lutheran Hospital
🇺🇸
Wheat Ridge, Colorado, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸
Hartford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
🇺🇸
North Haven, Connecticut, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
Baptist MD Anderson Cancer Center
🇺🇸
Jacksonville, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸
Savannah, Georgia, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸
Honolulu, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Saint Luke's Cancer Institute - Boise
🇺🇸
Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸
Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸
Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸
Post Falls, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸
Twin Falls, Idaho, United States
Illinois CancerCare-Bloomington
🇺🇸
Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸
Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸
Carthage, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸
Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Carle Physician Group-Effingham
🇺🇸
Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸
Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸
Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸
Galesburg, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸
Geneva, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸
Kewanee, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸
Lake Forest, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸
Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸
Mattoon, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸
O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸
Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸
Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸
Princeton, Illinois, United States
UW Health Carbone Cancer Center Rockford
🇺🇸
Rockford, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Springfield Clinic
🇺🇸
Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸
Springfield, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Mission Cancer and Blood - Des Moines
🇺🇸
Des Moines, Iowa, United States
Broadlawns Medical Center
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Mission Cancer and Blood - Laurel
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Trinity Regional Medical Center
🇺🇸
Fort Dodge, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Methodist West Hospital
🇺🇸
West Des Moines, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸
West Des Moines, Iowa, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸
Great Bend, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸
Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸
Liberal, Kansas, United States
Cancer Center of Kansas-Manhattan
🇺🇸
Manhattan, Kansas, United States
Cancer Center of Kansas - McPherson
🇺🇸
McPherson, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Wichita
🇺🇸
Wichita, Kansas, United States
Wesley Medical Center
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
Flaget Memorial Hospital
🇺🇸
Bardstown, Kentucky, United States
Jewish Hospital
🇺🇸
Louisville, Kentucky, United States
Saints Mary and Elizabeth Hospital
🇺🇸
Louisville, Kentucky, United States
UofL Health Medical Center Northeast
🇺🇸
Louisville, Kentucky, United States
Baton Rouge General Medical Center
🇺🇸
Baton Rouge, Louisiana, United States
Hematology/Oncology Clinic PLLC
🇺🇸
Baton Rouge, Louisiana, United States
Tulane University School of Medicine
🇺🇸
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Lahey Hospital and Medical Center
🇺🇸
Burlington, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸
Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸
Battle Creek, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸
Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
🇺🇸
Brighton, Michigan, United States
Henry Ford Cancer Institute-Downriver
🇺🇸
Brownstown, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸
Canton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸
Canton, Michigan, United States
Chelsea Hospital
🇺🇸
Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸
Chelsea, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸
Clinton Township, Michigan, United States
Corewell Health Dearborn Hospital
🇺🇸
Dearborn, Michigan, United States
Henry Ford Medical Center-Fairlane
🇺🇸
Dearborn, Michigan, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Henry Ford Health Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Henry Ford River District Hospital
🇺🇸
East China Township, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸
Grand Rapids, Michigan, United States
Henry Ford Saint John Hospital - Academic
🇺🇸
Grosse Pointe Woods, Michigan, United States
Henry Ford Saint John Hospital - Breast
🇺🇸
Grosse Pointe Woods, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸
Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸
Livonia, Michigan, United States
Henry Ford Saint John Hospital - Macomb Medical
🇺🇸
Macomb, Michigan, United States
Henry Ford Warren Hospital - Breast Macomb
🇺🇸
Macomb, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸
Muskegon, Michigan, United States
Henry Ford Medical Center-Columbus
🇺🇸
Novi, Michigan, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
🇺🇸
Pontiac, Michigan, United States
Lake Huron Medical Center
🇺🇸
Port Huron, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸
Reed City, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸
Saginaw, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸
Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸
Saint Joseph, Michigan, United States
Bhadresh Nayak MD PC-Sterling Heights
🇺🇸
Sterling Heights, Michigan, United States
Munson Medical Center
🇺🇸
Traverse City, Michigan, United States
Advanced Breast Care Center PLLC
🇺🇸
Warren, Michigan, United States
Henry Ford Health Warren Hospital
🇺🇸
Warren, Michigan, United States
Henry Ford Madison Heights Hospital - Breast
🇺🇸
Warren, Michigan, United States
Henry Ford Warren Hospital - GLCMS
🇺🇸
Warren, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸
Bemidji, Minnesota, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Essentia Health - Deer River Clinic
🇺🇸
Deer River, Minnesota, United States
Essentia Health Cancer Center
🇺🇸
Duluth, Minnesota, United States
Essentia Health Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸
Duluth, Minnesota, United States
Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Lake Region Healthcare Corporation-Cancer Care
🇺🇸
Fergus Falls, Minnesota, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Essentia Health Hibbing Clinic
🇺🇸
Hibbing, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸
Minneapolis, Minnesota, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Essentia Health Sandstone
🇺🇸
Sandstone, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Lakeview Hospital
🇺🇸
Stillwater, Minnesota, United States
Essentia Health Virginia Clinic
🇺🇸
Virginia, Minnesota, United States
Parkland Health Center-Bonne Terre
🇺🇸
Bonne Terre, Missouri, United States
Saint Francis Medical Center
🇺🇸
Cape Girardeau, Missouri, United States
Southeast Cancer Center
🇺🇸
Cape Girardeau, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸
Creve Coeur, Missouri, United States
MU Health Care Goldschmidt Cancer Center
🇺🇸
Jefferson City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Kansas City Veterans Affairs Medical Center
🇺🇸
Kansas City, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸
Rolla, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸
Rolla, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸
Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸
Saint Peters, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸
Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸
Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸
Sunset Hills, Missouri, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸
Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Community Medical Center
🇺🇸
Missoula, Montana, United States
Nebraska Medicine-Bellevue
🇺🇸
Bellevue, Nebraska, United States
Nebraska Cancer Specialists/Oncology Hematology West PC
🇺🇸
Grand Island, Nebraska, United States
CHI Health Good Samaritan
🇺🇸
Kearney, Nebraska, United States
Nebraska Medicine-Village Pointe
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Carson Tahoe Regional Medical Center
🇺🇸
Carson City, Nevada, United States
Cancer and Blood Specialists-Henderson
🇺🇸
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸
Henderson, Nevada, United States
Las Vegas Cancer Center-Henderson
🇺🇸
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸
Henderson, Nevada, United States
GenesisCare USA - Henderson
🇺🇸
Henderson, Nevada, United States
University Medical Center of Southern Nevada
🇺🇸
Las Vegas, Nevada, United States
Cancer and Blood Specialists-Shadow
🇺🇸
Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸
Las Vegas, Nevada, United States
GenesisCare USA - Las Vegas
🇺🇸
Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
🇺🇸
Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸
Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-San Martin
🇺🇸
Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸
Las Vegas, Nevada, United States
Ann M Wierman MD LTD
🇺🇸
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸
Las Vegas, Nevada, United States
GenesisCare USA - Vegas Tenaya
🇺🇸
Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
🇺🇸
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸
Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸
Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
GenesisCare USA - Fort Apache
🇺🇸
Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸
Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
🇺🇸
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸
Las Vegas, Nevada, United States
University Cancer Center
🇺🇸
Las Vegas, Nevada, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Saint Mary's Regional Medical Center
🇺🇸
Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸
Lake Success, New York, United States
North Shore University Hospital
🇺🇸
Manhasset, New York, United States
Long Island Jewish Medical Center
🇺🇸
New Hyde Park, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸
New York, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸
Clinton, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸
Goldsboro, North Carolina, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
Margaret R Pardee Memorial Hospital
🇺🇸
Hendersonville, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸
Jacksonville, North Carolina, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸
Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸
Fargo, North Dakota, United States
Good Samaritan Hospital - Cincinnati
🇺🇸
Cincinnati, Ohio, United States
TriHealth Cancer Institute-Westside
🇺🇸
Cincinnati, Ohio, United States
TriHealth Cancer Institute-Anderson
🇺🇸
Cincinnati, Ohio, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Mount Carmel East Hospital
🇺🇸
Columbus, Ohio, United States
Columbus Oncology and Hematology Associates Inc
🇺🇸
Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
The Mark H Zangmeister Center
🇺🇸
Columbus, Ohio, United States
Mount Carmel Health Center West
🇺🇸
Columbus, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸
Dayton, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Saint Rita's Medical Center
🇺🇸
Lima, Ohio, United States
Marietta Memorial Hospital
🇺🇸
Marietta, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸
Maumee, Ohio, United States
Licking Memorial Hospital
🇺🇸
Newark, Ohio, United States
Springfield Regional Cancer Center
🇺🇸
Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸
Springfield, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Providence Saint Vincent Medical Center
🇺🇸
Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸
Bryn Mawr, Pennsylvania, United States
Main Line Health Center-Collegeville
🇺🇸
Collegeville, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Main Line Health Center-Exton
🇺🇸
Exton, Pennsylvania, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸
Hazleton, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸
Lewisburg, Pennsylvania, United States
Riddle Memorial Hospital
🇺🇸
Media, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸
Paoli, Pennsylvania, United States
Geisinger Cancer Services-Pottsville
🇺🇸
Pottsville, Pennsylvania, United States
Geisinger Medical Oncology-Selinsgrove
🇺🇸
Selinsgrove, Pennsylvania, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Lankenau Medical Center
🇺🇸
Wynnewood, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
Saint Francis Cancer Center
🇺🇸
Greenville, South Carolina, United States
Self Regional Healthcare
🇺🇸
Greenwood, South Carolina, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Sanford Cancer Center Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Swedish Cancer Institute-Edmonds
🇺🇸
Edmonds, Washington, United States
PeaceHealth Saint John Medical Center
🇺🇸
Longview, Washington, United States
MultiCare Good Samaritan Hospital
🇺🇸
Puyallup, Washington, United States
Swedish Medical Center-Ballard Campus
🇺🇸
Seattle, Washington, United States
FHCC South Lake Union
🇺🇸
Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸
Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸
Seattle, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸
Vancouver, Washington, United States
West Virginia University Charleston Division
🇺🇸
Charleston, West Virginia, United States
Duluth Clinic Ashland
🇺🇸
Ashland, Wisconsin, United States
Northwest Wisconsin Cancer Center
🇺🇸
Ashland, Wisconsin, United States
Marshfield Clinic-Chippewa Center
🇺🇸
Chippewa Falls, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸
Eau Claire, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
Marshfield Medical Center - Ladysmith
🇺🇸
Ladysmith, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸
Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸
Minocqua, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸
New Richmond, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸
Stevens Point, Wisconsin, United States
Marshfield Clinic-Wausau Center
🇺🇸
Wausau, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸
Weston, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸
Wisconsin Rapids, Wisconsin, United States

Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts