Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma
- Conditions
- LymphomaMantle Cell Lymphoma
- Interventions
- Registration Number
- NCT01415752
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.
PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* To determine whether the addition of bortezomib (RBV) to an induction regimen of rituximab-bendamustine (RB) improves progression-free survival (PFS) compared to RB alone in patients with previously untreated mantle cell lymphoma.
* To determine whether the addition of lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV improves PFS compared to consolidation rituximab alone in this patient population.
Secondary
* To determine whether the addition of bortezomib to induction therapy improves the positron emission tomography (PET)-documented complete response (CR) rate compared to RB alone.
* To determine the objective response rate (ORR) for RB and RBV.
* Among patients who do not have PET-documented CR at the end of induction, to determine whether the addition of lenalidomide to consolidation therapy improves CR and ORR compared with rituximab alone.
* To determine overall survival (OS) in the treatment arms.
* To determine safety, with attention to the addition of bortezomib in the induction regimen and lenalidomide-rituximab (LR) as consolidation therapy.
Laboratory
* To collect paraffin-embedded tissue for creation of tissue microarray.
* To collect and bank serum and blood mononuclear cells for future studies.
* To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11 expression by immunohistochemistry; and Micro-RNA levels by microarray).
Quality of Life
* Using patient-reported outcomes data, to determine the extent and severity of neuropathy associated with the addition of bortezomib to induction treatment.
* Using patient-reported outcomes data, to determine the extent and severity of fatigue associated with the addition of lenalidomide to consolidation treatment.
* To evaluate the effects of the addition of bortezomib and lenalidomide on patient-reported health-related quality of life.
* To evaluate the effects of bortezomib-related neuropathy on patient-reported health-related quality of life.
* To evaluate the response of lymphoma-specific symptoms to treatment.
* Using longitudinal patient-reported outcomes data, to describe the trajectory of lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life prior to, during, and following treatment among older adults with MCL.
Imaging
* To assess the proportion of patients up and down staging when fludeoxyglucose F 18- (FDG) PET/CT is added to standard Ann Arbor staging.
* To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and PFS.
* Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the correlation of interim FDG-PET/CT imaging with response rate and PFS both during induction and consolidation therapy.
* To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total tumor burden, and association with pathology features (blastoid variant vs other, and Ki67) in the setting of MCL.
* To assess differences in overall and CR rates when using Deauville vs International Harmonization Project FDG-PET/CT interpretation criteria.
* To determine whether there is a correlation between FDG-PET/CT response and residual disease assessment by molecular and/or flow cytometric techniques.
Residual Disease Assessment by Molecular and Flow Cytometric Techniques
* To determine whether the number of malignant cells in circulation predict the number of cells in marrow.
* To determine whether the number of malignant cells in circulation/in marrow at the end of induction correlate with CR and 2-year PFS.
* To determine whether there is a higher rate of minimal residual disease (MRD) negativity among patients randomized to RBV as compared with RB, and among patients treated with LR maintenance compared with rituximab.
* To compare the two methods of MRD detection - molecular techniques and flow cytometry - as prognostic markers for outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients are randomized to 1 of 4 treatment arms.
* Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm C: Patients receive induction therapy comprising rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood and bone marrow sample collection at baseline and during treatment for correlative studies.
Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires at baseline and periodically during study and follow up.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 10 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 373
-
Mantle Cell Lymphoma International Prognostic Index (MIPI) score must be calculated and entered in OPEN
-
Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
-
Patients must have at least one objective measurable disease parameter
-
Negative pregnancy test
-
Women of childbearing potential and sexually active males use an accepted and effective method of contraception
-
ECOG performance status 0-2
-
Absolute neutrophil count (ANC) ≥ 1,500/mcL (1.5 x 10^9/L)
-
Platelets ≥ 100,000/mcL (100 x 10^9/L)
-
Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2 times upper limit of normal (ULN)
-
Bilirubin ≤ 2 times ULN
-
Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
-
Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist. Patients must have no medical contra-indications to, and be willing to take, DVT prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have deep vein thrombosis (DVT) prophylaxis. Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have full anticoagulation, therapeutic doses of low molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0, or any other accepted full anticoagulation regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with appropriate monitoring for that agent. Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen. Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing prothrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips).
-
HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:
- HIV is sensitive to antiretroviral therapy
- Must be willing to take effective antiretroviral therapy, if indicated
- CD4 count at screening >= 300 cells/mm³
- If on antiretroviral therapy, must not be taking zidovudine or stavudine
- Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later
Step 1 (Induction)
- Women (sexually mature female) must not be pregnant or breast-feeding
- Evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, low grade prostate carcinoma (Gleason grade ≤ 6) managed with observation that has been stable for at least 6 months, or any malignancy treated with curative intent continuously disease free for >=3 years so as not to interfere with interpretation of radiographic response
- Prior therapy for MCL, except: < 2 weeks of steroid therapy for symptom control or local radiation therapy for symptom control if there is measurable disease outside the radiation portal. Patients may be on chronic steroids for non-malignant disease if on a stable dose equivalent to ≤ 20 mg prednisone per day.
- CNS involvement
- History of AIDS-defining conditions
- Grade 2 or greater peripheral neuropathy.
- NYHA Class III or IV heart failure, uncontrolled angina severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
- Hypersensitivity to bortezomib, boron or mannitol
- A serious medical or psychiatric illness likely to interfere with study participation
- Participating in any other therapeutic clinical trial or taking any other experimental medications within 14 days prior to registration.
Step 2 (Maintenance) Inclusion Criteria:
-
ECOG performance status between 0-2
-
Complete response, partial response or stable disease after Step 1
-
ANC >= 1000 cells/mm3 (1.0 x 10^9/L)
-
Platelets >= 75,000 cells/mm3 (75 x 10^9/L)
-
AST/ALT <= 2 x upper limit of normal (ULN)
-
Total bilirubin <= 2 x upper limit of normal (ULN) or, if total elevated, direct bilirubin <= 2 x upper limit of normal (ULN)
-
Calculated creatinine clearance by Cockroft-Gault formula >= 30 ml/min
-
Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory REMS program, and be willing and able to comply with the requirements of REMS.
- Pregnancy tests must occur within 10 - 14 days and again within 24 hours prior to initiation of Cycle 1 of lenalidomide.
- Females of childbearing potential (FCBP)* with regular or no menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days while on lenalidomide therapy (including breaks in therapy); at discontinuation of lenalidomide and at Day 28 post the last dose of lenalidomide. Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 14 days while on lenalidomide therapy (including breaks in therapy), at discontinuation of lenalidomide and at Day 14 and Day 28 post the last dose of lenalidomide (see Appendix VI: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods).
- 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 and must either commit to continued abstinence 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 she starts taking 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- A female of childbearing potential is any sexually mature female, regardless of sexual orientation of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).
- Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study/lenaliomide: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study including interruptions in therapy; and 3) for at least 28 days after discontinuation/stopping lenalidomide. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.
- Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment.
- Males must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment. All males, regardless of whether they have undergone a successful vasectomy, must agree to use a latex condom during sexual contact with a female of childbearing potential, or to practice complete abstinence from heterosexual intercourse with any female of childbearing potential during all cycles of study treatment and for at least 28 days following discontinuation of protocol treatment
- Patients must have no medical contra-indications to, and be willing to take, DVT prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have deep vein thrombosis (DVT) prophylaxis. Patients randomized to Arms G or H who have full anticoagulation, a history of a thrombotic vascular event will be required to have therapeutic doses of low molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0, or any other accepted full anticoagulation regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with appropriate monitoring for that agent. Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen. Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing pro-thrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab rituximab Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab Bendamustine Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab rituximab Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab Bendamustine Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab bortezomib Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab rituximab Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab Bendamustine Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab lenalidomide Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab rituximab Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab Bendamustine Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab bortezomib Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab lenalidomide Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) for Induction Phase Assessed at baseline, every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months PFS is defined as time from randomization to lymphoma progression or death. Progression is defined as:
* Appearance of any new lesion \>1.5 cm in any axis during or at the end of therapy
* \>=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions.
* \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.
* Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systemsProgression-free Survival (PFS) for Maintenance Phase (Step 2) Assessed at registration to step 2, cycles 6, 12, 18, treatment completion, then every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months PFS is defined as time from Step 2 registration to lymphoma progression or death. Progression is defined as:
* Appearance of any new lesion \>1.5 cm in any axis during or at the end of therapy
* \>=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions.
* \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.
* Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
- Secondary Outcome Measures
Name Time Method PET-documented Complete Response for Induction Phase (Step 1) Assessed at baseline and 24 weeks (end of cycle 6) Complete response is defined as disappearance of all detectable clinical evidence of disease.
Overall Survival (OS) Rate at 5 Years Since Maintenance (Step 2) Assessed every 3 months for 2.5 years, every 6 months for years 2.5-5 OS is defined as the time from registration of Step 2 (maintenance) until death from any cause or last know alive. The Kaplan-Meier estimate of 5-year OS rate is reported.
Objective Response for Induction Phase (Step 1) Assessed at baseline and 24 weeks (end of cycle 6) Objective response is defined as either complete response (CR) or partial response (PR).
CR is defined as disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
PR is defined as:
* ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses
* No increase in the size of other nodes, liver or spleen.
* Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified, e.g. large-cell lymphoma or small cleaved cell lymphoma.
* No new sites of disease.
* Patients who achieve a CR but have persistent morphologic bone marrow involvement will be considered partial responders.
* When the bone marrow was involved before therapy and a clinical CR was achieved, but with no bone marrow assessment after treatment, patients are considered partial responders.Objective Response for Maintenance (Step 2) Among Patients Without PET-documented CR at the End of Induction Assessed at baseline and every 4 months for 2 years Objective response is defined as either complete response (CR) or partial response (PR).
CR is defined as disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
PR is defined as:
* ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses
* No increase in the size of other nodes, liver or spleen.
* Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified, e.g. large-cell lymphoma or small cleaved cell lymphoma.
* No new sites of disease.
* Patients who achieve a CR but have persistent morphologic bone marrow involvement will be considered partial responders.
* When the bone marrow was involved before therapy and a clinical CR was achieved, but with no bone marrow assessment after treatment, patients are considered partial responders.
Trial Locations
- Locations (416)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Mount Sinai Hospital Medical Center
🇺🇸Chicago, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Oncology and Hematology Care Inc-Taft
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc - Kenwood
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Blue Ash
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Kaiser Permanente-San Francisco
🇺🇸San Francisco, California, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Rocky Mountain Oncology
🇺🇸Casper, Wyoming, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Kalispell Medical Oncology
🇺🇸Kalispell, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Montana Cancer Consortium CCOP
🇺🇸Billings, Montana, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Stanford University Hospitals and Clinics
🇺🇸Stanford, California, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Kaiser Permanente-Santa Rosa
🇺🇸Santa Rosa, California, United States
Kaiser Permanente, Fremont
🇺🇸Fremont, California, United States
Kaiser Permanente-South San Francisco
🇺🇸South San Francisco, California, United States
Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸Antioch, California, United States
Kaiser Permanente-Stockton
🇺🇸Stockton, California, United States
Kaiser Permanente
🇺🇸Fresno, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸Vacaville, California, United States
Kaiser Permanente-San Rafael
🇺🇸San Rafael, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸San Jose, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Rocky Mountain Cancer Centers-Penrose
🇺🇸Colorado Springs, Colorado, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
Christiana Care Health System-Wilmington Hospital
🇺🇸Wilmington, Delaware, United States
Christiana Gynecologic Oncology LLC
🇺🇸Newark, Delaware, United States
Saint Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Kaiser Permanente-Vallejo
🇺🇸Vallejo, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Delaware Clinical and Laboratory Physicians PA
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Regional Hematology and Oncology PA
🇺🇸Newark, Delaware, United States
Rocky Mountain Cancer Centers-Sky Ridge
🇺🇸Lone Tree, Colorado, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸Highland Park, Illinois, United States
Presence Saint Mary's Hospital
🇺🇸Kankakee, Illinois, United States
SwedishAmerican Regional Cancer Center/ACT
🇺🇸Rockford, Illinois, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Kansas City CCOP
🇺🇸Prairie Village, Kansas, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸Ames, Iowa, United States
Franciscan Saint Anthony Health-Michigan City
🇺🇸Michigan City, Indiana, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
Saint Luke's South Hospital
🇺🇸Overland Park, Kansas, United States
McFarland Clinic PC-Boone
🇺🇸Boone, Iowa, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Woodland Cancer Care Center
🇺🇸Michigan City, Indiana, United States
Reid Hospital and Health Care Services
🇺🇸Richmond, Indiana, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
IU Health Arnett Cancer Care
🇺🇸Lafayette, Indiana, United States
Cedar Rapids Oncology Association
🇺🇸Cedar Rapids, Iowa, United States
Simonds-Sinon Regional Cancer Center
🇺🇸Fitchburg, Massachusetts, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Spectrum Health Big Rapids Hospital
🇺🇸Big Rapids, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Frontier Cancer Center and Blood Institute-Billings
🇺🇸Billings, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Metro-Minnesota CCOP
🇺🇸Saint Louis Park, Minnesota, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Parkland Health Center-Bonne Terre
🇺🇸Bonne Terre, Missouri, United States
Lakeland Hospital
🇺🇸Saint Joseph, Michigan, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸East Syracuse, New York, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Norris Cotton Cancer Center Nashua
🇺🇸Nashua, New Hampshire, United States
Phelps County Regional Medical Center
🇺🇸Rolla, Missouri, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Sanford Clinic North-Fargo
🇺🇸Fargo, North Dakota, United States
Southeastern Medical Oncology Center-Wilson
🇺🇸Wilson, North Carolina, United States
Summa Barberton Hospital
🇺🇸Barberton, Ohio, United States
Orange Regional Medical Center
🇺🇸Middletown, New York, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸Akron, Ohio, United States
Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Oncology Hematology Care Inc - Anderson
🇺🇸Cincinnati, Ohio, United States
Hematology Oncology Associates of Central New York-Rome
🇺🇸Rome, New York, United States
Saint John's Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Glens Falls Hospital
🇺🇸Glens Falls, New York, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Park Ridge Hospital Breast Health Center
🇺🇸Hendersonville, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸Clinton, North Carolina, United States
Kinston Medical Specialists PA
🇺🇸Kinston, North Carolina, United States
Oncology Hematology Care Inc-Mercy West
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
University Pointe
🇺🇸West Chester, Ohio, United States
Mercy Cancer Center-Elyria
🇺🇸Elyria, Ohio, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Dayton CCOP
🇺🇸Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸Dayton, Ohio, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Tulsa Cancer Institute
🇺🇸Tulsa, Oklahoma, United States
Providence Milwaukie Hospital
🇺🇸Milwaukie, Oregon, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Seattle Cancer Care Alliance at EvergreenHealth
🇺🇸Kirkland, Washington, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
Pottstown Memorial Medical Center
🇺🇸Pottstown, Pennsylvania, United States
Southwest VA Regional Cancer Center
🇺🇸Norton, Virginia, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Wellmont Medical Associates Oncology and Hematology-Bristol
🇺🇸Bristol, Tennessee, United States
Memorial Hospital Of Martinsville
🇺🇸Martinsville, Virginia, United States
Wellmont Holston Valley Hospital and Medical Center
🇺🇸Kingsport, Tennessee, United States
EvergreenHealth Medical Center
🇺🇸Kirkland, Washington, United States
Skagit Valley Hospital
🇺🇸Mount Vernon, Washington, United States
Compass Oncology Vancouver
🇺🇸Vancouver, Washington, United States
Olympic Medical Center
🇺🇸Port Angeles, Washington, United States
Cancer Care Northwest-Valley
🇺🇸Spokane, Washington, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸Johnson Creek, Wisconsin, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States
Marshfield Clinic Cancer Center at Sacred Heart
🇺🇸Eau Claire, Wisconsin, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Green Bay Oncology at Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Olympic Medical Cancer Care Center
🇺🇸Sequim, Washington, United States
Agnesian Cancer Center
🇺🇸Fond Du Lac, Wisconsin, United States
Holy Family Memorial Hospital
🇺🇸Manitowoc, Wisconsin, United States
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Green Bay Oncology - Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Waukesha Memorial Hospital - ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Marshfield Clinic at James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
Oconomowoc Memorial Hospital-ProHealth Care Inc
🇺🇸Oconomowoc, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
Big Horn Basin Cancer Center
🇺🇸Cody, Wyoming, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Marshfield Clinic-Wausau Center
🇺🇸Wausau, Wisconsin, United States
The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Kaiser Permanente-Franklin
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers-Rose
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers-Midtown
🇺🇸Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸Denver, Colorado, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Western Oncology Research Consortium
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
Liberty Radiation Oncology Center
🇺🇸Liberty, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Saint John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Missouri Baptist Outpatient Center-Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Wellmont Bristol Regional Medical Center
🇺🇸Bristol, Tennessee, United States
Wellmont Medical Associates Oncology and Hematology-Kingsport
🇺🇸Kingsport, Tennessee, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
Mercy Medical Center
🇺🇸Durango, Colorado, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
Comprehensive Cancer Care and Research Institute of Colorado LLC
🇺🇸Englewood, Colorado, United States
Southwest Oncology PC
🇺🇸Durango, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Kaiser Permanente-Lone Tree
🇺🇸Lone Tree, Colorado, United States
Littleton Adventist Hospital
🇺🇸Littleton, Colorado, United States
Rocky Mountain Cancer Centers-Longmont
🇺🇸Longmont, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Rocky Mountain Cancer Centers-Thornton
🇺🇸Thornton, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Rocky Mountain Cancer Centers - Pueblo
🇺🇸Pueblo, Colorado, United States
Rocky Mountain Cancer Centers-Aurora
🇺🇸Aurora, Colorado, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Mercy Health Mercy Campus
🇺🇸Muskegon, Michigan, United States
Lakeland Community Hospital
🇺🇸Niles, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Spectrum Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
McFarland Clinic PC-Marshalltown
🇺🇸Marshalltown, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
McFarland Clinic PC-Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
Saint Clare's Hospital
🇺🇸Weston, Wisconsin, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Saint John Medical Center
🇺🇸Longview, Washington, United States
Skagit Valley Hospital Regional Cancer Care Center
🇺🇸Mount Vernon, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
🇺🇸Springfield, Missouri, United States
Green Bay Oncology - Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Kaiser Permanente-Modesto
🇺🇸Modesto, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Redwood City
🇺🇸Redwood City, California, United States
Kaiser Permanente-Richmond
🇺🇸Richmond, California, United States
Kaiser Permanente San Leandro
🇺🇸San Leandro, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸Walnut Creek, California, United States
Rocky Mountain Cancer Centers-Boulder
🇺🇸Boulder, Colorado, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers-Greenwood Village
🇺🇸Greenwood Village, Colorado, United States
Kaiser Permanente-Rock Creek
🇺🇸Lafayette, Colorado, United States
Mountain Blue Cancer Care Center
🇺🇸Golden, Colorado, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Rocky Mountain Cancer Centers-Lakewood
🇺🇸Lakewood, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Rocky Mountain Cancer Centers-Parker
🇺🇸Parker, Colorado, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Nanticoke Memorial Hospital
🇺🇸Seaford, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
Oncare Hawaii Inc-Pali Momi
🇺🇸'Aiea, Hawaii, United States
Pali Momi Medical Center
🇺🇸'Aiea, Hawaii, United States
Castle Medical Center
🇺🇸Kailua, Hawaii, United States
Idaho Urologic Institute-Meridian
🇺🇸Meridian, Idaho, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸Lihue, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Kootenai Cancer Center
🇺🇸Post Falls, Idaho, United States
Kootenai Cancer
🇺🇸Sandpoint, Idaho, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Cancer Care Center of Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
North Shore Hematology Oncology
🇺🇸Libertyville, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸Skokie, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸Niles, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Hematology Oncology Associates-Quad Cities
🇺🇸Bettendorf, Iowa, United States
McFarland Clinic PC-Jefferson
🇺🇸Jefferson, Iowa, United States
Ochsner Health Center-Summa
🇺🇸Baton Rouge, Louisiana, United States
Oncology Hematology Care Inc-Crestview
🇺🇸Crestview Hills, Kentucky, United States
Penobscot Bay Medical Center
🇺🇸Rockport, Maine, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Franklin Square Hospital Center
🇺🇸Baltimore, Maryland, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Green Bay Oncology - Escanaba
🇺🇸Escanaba, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Grand Rapids Clinical Oncology Program
🇺🇸Grand Rapids, Michigan, United States
Mercy Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
Genesys Regional Medical Center
🇺🇸Grand Blanc, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Green Bay Oncology - Iron Mountain
🇺🇸Iron Mountain, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Sanford Clinic North-Bemidgi
🇺🇸Bemidji, Minnesota, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Fairview-Southdale Hospital
🇺🇸Edina, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Centerpoint Medical Center LLC
🇺🇸Independence, Missouri, United States
Capital Region Medical Center-Goldschmidt Cancer Center
🇺🇸Jefferson City, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Veterans Adminstration New Jersey Health Care System
🇺🇸East Orange, New Jersey, United States
Hematology Oncology Associates of Central New York-Liverpool
🇺🇸Liverpool, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Hematology Oncology Associates of Central New York-Onondaga Hill
🇺🇸Syracuse, New York, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸Goldsboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸Jacksonville, North Carolina, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Cleveland Clinic Cancer Center Beachwood
🇺🇸Beachwood, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Samaritan North Health Center
🇺🇸Dayton, Ohio, United States
Oncology Hematology Care Inc-Healthplex
🇺🇸Fairfield, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Cleveland Clinic Cancer Center Mansfield
🇺🇸Mansfield, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Cleveland Clinic Cancer Center Strongsville
🇺🇸Strongsville, Ohio, United States
Cleveland Clinic Wooster Specialty Center
🇺🇸Wooster, Ohio, United States
Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
Lake University Ireland Cancer Center
🇺🇸Mentor, Ohio, United States
UH-Seidman Cancer Center at Saint John Medical Center
🇺🇸Westlake, Ohio, United States
South Pointe Hospital
🇺🇸Warrensville Heights, Ohio, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸Hazleton, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Geisinger Medical Oncology at Evangelical Community Hospital
🇺🇸Lewisburg, Pennsylvania, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Geisinger Medical Oncology-Pottsville
🇺🇸Pottsville, Pennsylvania, United States
AnMed Health Cancer Center
🇺🇸Anderson, South Carolina, United States
Upstate Carolina CCOP
🇺🇸Spartanburg, South Carolina, United States
Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Wenatchee Valley Hospital and Clinics
🇺🇸Wenatchee, Washington, United States
Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Marshfield Clinic-Rice Lake Center
🇺🇸Rice Lake, Wisconsin, United States
Saint Nicholas Hospital
🇺🇸Sheboygan, Wisconsin, United States
Marshfield Clinic Cancer Care at Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Billings Clinic-Cody
🇺🇸Cody, Wyoming, United States
Kaiser Permanente-South Sacramento
🇺🇸Sacramento, California, United States
Kaiser Permanente - Sacramento
🇺🇸Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Straub Clinic and Hospital
🇺🇸Honolulu, Hawaii, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Hendersonville Hematology and Oncology at Pardee
🇺🇸Hendersonville, North Carolina, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Comprehensive Cancer Care PC
🇺🇸Saint Louis, Missouri, United States
Cancer Care Northwest-North Spokane
🇺🇸Spokane, Washington, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Geisinger Wyoming Valley
🇺🇸Wilkes-Barre, Pennsylvania, United States
OnCare Hawaii-Liliha
🇺🇸Honolulu, Hawaii, United States
Oncare Hawaii Inc-Kuakini
🇺🇸Honolulu, Hawaii, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸Kansas City, Missouri, United States
Oncare Hawaii Inc-POB II
🇺🇸Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Ochsner Baptist Medical Center
🇺🇸New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Massey Cancer Center at Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Hematology Oncology Associates of Central New York-Auburn
🇺🇸Auburn, New York, United States
Rocky Mountain Cancer Centers-Littleton
🇺🇸Littleton, Colorado, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Carle on Vermilion
🇺🇸Danville, Illinois, United States
North Coast Cancer Care
🇺🇸Sandusky, Ohio, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
Cleveland Clinic Cancer Center Independence
🇺🇸Independence, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸Mayfield Heights, Ohio, United States