A Phase II Study of Obinutuzumab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Lenalidomide
- Conditions
- Ann Arbor Stage II Grade 1 Follicular Lymphoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Progression Free Survival
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This phase II trial studies how well obinutuzumab and lenalidomide work in treating patients with previously untreated stage II-IV grade 1-3a follicular lymphoma. Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, 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. Giving obinutuzumab and lenalidomide may work better in treating patients with previously untreated follicular lymphoma.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the efficacy of obinutuzumab combined with lenalidomide in patients with previously untreated follicular lymphoma (FL) (determined by progression-free survival \[PFS\] at 2 years). SECONDARY OBJECTIVES: I. To evaluate the safety of obinutuzumab in combination with lenalidomide in patients with untreated follicular lymphoma. II. To evaluate the efficacy of obinutuzumab in combination with lenalidomide in subjects with follicular lymphoma as assessed by complete remission (CR) at 30 months, overall response rate (ORR), duration of response (DOR), event free survival (EFS), and overall survival (OS). EXPLORATORY OBJECTIVES: I. To evaluate prognostic and predictive biomarkers relative to treatment outcomes. OUTLINE: Patients receive obinutuzumab intravenously (IV) over 4-6 hours on days 1, 8, and 15 of course 1 and day 1 of courses 2-6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR or complete remission unconfirmed (CRu) may receive up to an additional 12 courses of lenalidomide. After completion of study treatment, patients are followed up every 6 months for 18 months and then every year for up to 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated
- •Able and willing to provide written informed consent and to comply with the study protocol
- •Bi-dimensionally measurable disease, with at least one mass lesion \>= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
- •Must be in need of therapy as evidenced by at least one of the following criteria:
- •Bulky disease defined as:
- •A nodal or extranodal (except spleen) mass \> 7 cm in its greater diameter or,
- •At least 3 nodal or extranodal sites \>= 3 cm in diameter
- •Presence of at least one B symptom:
- •Fever (\> 38 C) not due to infectious etiology
- •Night sweats
Exclusion Criteria
- •Known active central nervous system lymphoma or leptomeningeal disease
- •Follicular lymphoma with evidence of diffuse large B-cell transformation
- •Grade 3b follicular lymphoma
- •Any prior history of other malignancy besides follicular lymphoma, unless the patient has been free of disease for \>= 5 years and felt to be at low risk for recurrence by the treating physician, except:
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated cervical carcinoma in situ without evidence of disease
- •Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of lenalidomide capsules, or put the study outcomes at undue risk
- •Known history of human immunodeficiency virus (HIV), active hepatitis C virus, active hepatitis B virus infection, or any uncontrolled active systemic infection
- •Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated
- •Prior use of lenalidomide
Arms & Interventions
Treatment (obinutuzumab, lenalidomide)
Patients receive obinutuzumab IV over 4-6 hours on days 1, 8, and 15 of course 1 and day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR or CRu may receive up to an additional 12 cycles of lenalidomide.
Intervention: Lenalidomide
Treatment (obinutuzumab, lenalidomide)
Patients receive obinutuzumab IV over 4-6 hours on days 1, 8, and 15 of course 1 and day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR or CRu may receive up to an additional 12 cycles of lenalidomide.
Intervention: Obinutuzumab
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: approximately 71 months
Will be calculated and corresponding 95% confidence interval (CI) will be derived.
Secondary Outcomes
- Complete Response(24 months)
- Overall Response Rate (CR + Partial Response [PR])(24 months)
- Duration of Response(From the time by which measurement criteria for CR or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 3 years)
- Overall Survival(From the date of course 1, day 1 to the date of death regardless of cause, assessed up to 3 years)
- Event Free Survival(From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death, assessed up to 3 years)