An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib
- Conditions
- Ann Arbor Stage II Follicular Lymphoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This phase II trial studies how well ibrutinib in combination with rituximab and lenalidomide works in treating patients with previously untreated, stage II-IV follicular lymphoma or marginal zone lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. 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. Giving ibrutinib in combination with rituximab and lenalidomide may work better in treating follicular lymphoma or marginal zone lymphoma.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) and marginal zone lymphoma (determined by progression-free survival at 2 years). SECONDARY OBJECTIVES: I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by complete response rate (CR) at 120 weeks, overall response rate (ORR), duration of response (DOR), event free survival (EFS), time to next anti-lymphoma treatment (TTNT), and overall survival (OS). II. To evaluate the safety and tolerability of ibrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL and marginal zone lymphoma. EXPLORATORY OBJECTIVES: I. To evaluate prognostic and mechanistic biomarkers relative to treatment outcomes. OUTLINE: Patients receive lenalidomide orally (PO) on days 1-21, rituximab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 24 weeks for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed CD20+ follicular lymphoma, grade 1, 2, or 3a or marginal zone lymphoma
- •Have had no prior systemic treatment for lymphoma
- •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)
- •In the opinion of the investigator would benefit from systemic therapy
- •Stage II, III, or IV disease
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Absolute neutrophil count (ANC) \>= 1,000/mm\^3, independent of growth factor support (within 28 days prior to signing informed consent).
- •Platelet counts \>= 100,000/mm\^3 or \>= 50,000/mm\^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent).
- •Serum aspartate transaminase (AST) or alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)
- •Creatinine clearance \> 30 ml/min calculated by modified Cockcroft-Gault formula
Exclusion Criteria
- •Known central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission \> 6 months
- •Evidence of diffuse large B-cell transformation
- •Grade 3b FL
- •Any prior history of other malignancy besides FL or marginal zone 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 ibrutinib capsules, or put the study outcomes at undue risk, including but not limited to:
- •Moderate to severe hepatic impairment (Child-Pugh classes B and C)
- •Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or 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
Arms & Interventions
Treatment (lenalidomide, rituximab, ibrutinib)
Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib
Treatment (lenalidomide, rituximab, ibrutinib)
Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (lenalidomide, rituximab, ibrutinib)
Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Treatment (lenalidomide, rituximab, ibrutinib)
Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Rituximab
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 24 months
Evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated FL and marginal zone lymphoma (determined by PFS at 2 years). Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived. Kaplan-Meier method will be used to estimate the PFS. Corresponding 95% CI will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.
Secondary Outcomes
- Complete Response (CR) Rate(At 120 weeks)
- Overall Response Rate (ORR) (CR Rate + Partial Response [PR])(Up to 3 years)
- Duration of Response (DOR)(Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 71.2 months)
- Event Free Survival (EFS)(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 70.2 months)
- Time to Next Anti-lymphoma Treatment (TTNT)(From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 75.8 months)
- Overall Survival (OS) Rate(From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 78 months)