This phase II trial studies how well chemotherapy and lenalidomide followed by rituximab and lenalidomide work in treating patients with previously untreated mantle cell lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, 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. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells, and it may also prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with rituximab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Sequential chemotherapy and lenalidomide maintenance followed by rituximab and lenalidomide may be an effective treatment for mantle cell lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02633137.
PRIMARY OBJECTIVES:
I. Determine the 3-year progression-free survival (PFS) of the primary treatment program (lenalidomide [Len]-rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [RCHOP]->rituximab [R]-high-dose cytarabine [HiDAC]->R-Len maintenance).
SECONDARY OBJECTIVES:
I. Assess the 3-year PFS in different clinical risk subgroups, specified below: Low risk; marker of proliferation Ki-67 (Ki-67) < 10%; intermediate risk: Ki-67 10-30%; high risk: Ki-67 >= 30% or blastic/blastoid/pleomorphic morphology.
II. Assess if the mantle cell international prognostic index (M-IPI) is prognostically significant (correlated with PFS and overall survival [OS]) with this treatment program.
III. Assess the rate of positron emission tomography (PET)-negativity (Deauville 1, 2, or 3) at various time points and correlate with outcome (PFS).
IV. Evaluate minimal residual disease (MRD) status using a novel deep-sequencing platform at various time points and correlate with outcome (PFS).
V. Assess the 3-year overall survival (OS).
EXPLORATORY OBJECTIVE:
I. Collect serum and peripheral blood mononuclear cells to store in Memorial Sloan Kettering Cancer Center (MSKCC) tissue bank for future correlative studies.
OUTLINE:
INDUCTION PHASE: Patients receive lenalidomide orally (PO) on days 1-14. Patients also receive rituximab intravenously (IV), cyclophosphamide IV, doxorubicin IV and vincristine IV on day 1, and prednisone PO on days 1-5 or 2-6. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
R-HIDAC: Within 21-28 days of completion of the last course of induction cycle, patients not experiencing progressive disease receive rituximab IV on day 1 and then HIDAC IV over 3 hours every 12 hours on day 1. Treatment repeats every 3 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Within 3-5 weeks after R-HIDAC treatment, patients receive lenalidomide PO daily on days 1-21 and rituximab IV on day 1 every 8 weeks. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAnita Kumar
