Testing the Addition of a New Anti-Cancer Drug, Glofitamab to Usual Chemotherapy for Burkitt and Double Hit Lymphoma

PRIMARY OBJECTIVES: I. To compare the progression free survival (PFS) of rituximab (R)-chemotherapy plus glofitamab versus R-chemotherapy alone in patients with newly diagnosed Burkitt lymphoma. II. To compare the PFS of R-chemotherapy plus glofitamab versus R-chemotherapy alone in patients with newly diagnosed high grade (double hit) B-cell lymphoma with MYC and BCL2 rearrangements. III. To determine the overall survival of obinutuzumab, rituximab, ifosfamine, carboplatin, etoposide (RICE), and glofitamab in patients with relapsed Burkitt lymphoma. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) of R-chemotherapy plus glofitamab versus R-chemotherapy alone in patients with Burkitt lymphoma, and patients with high grade B-cell lymphoma with MYC and BCL2 rearrangements. II. To compare the safety and tolerability of glofitamab combined with R-chemotherapy versus R-chemotherapy alone in patients with Burkitt lymphoma, and patients with high grade B-cell lymphoma with MYC and BCL2 rearrangements. III. To determine the event free survival (EFS), complete response (CR) and overall response (OR) rates of obinutuzumab, RICE, and glofitamab in patients with relapsed Burkitt and high grade B-cell lymphoma. IV. To assess how many patients undergo transplant or chimeric antigen receptor T-cell therapy (CART) after treatment with obinutuzumab, RICE, and glofitamab for relapsed Burkitt lymphoma. EXPLORATORY OBJECTIVES: I. To assess patient reported outcomes in patients with Burkitt and double hit lymphoma at study enrollment, during treatment and at the end of therapy. II. To evaluate the completion rate of a lymphoma-specific patient assessment of life survey (PALS) for 7 patient directed questions on social determinants of health (SDH) and assess the impact of the survey collected data on outcomes for all enrolled patients. OUTLINE: Patients with newly diagnosed Burkitt lymphoma are assigned to cohort 1, patients with double hit lymphoma are assigned to cohort 2, patients with relapsed or refractory Burkitt lymphoma or high grade lymphoma are assigned to cohort 3. COHORT 1: Patients are randomized to 1 of 2 arms. Patients who received a singe cycle of anthracycline containing chemotherapy will start treatment at cycle 2 22-36 days after cycle 1. ARM 1: Patients receive either rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate (RCODOXM)/rituximab, ifosfamide, etoposide, cytarabine (RIVAC) or rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone (DA-REPOCH) treatment per the investigators choice. Patients over the age of 60 or with other co-morbidities are assigned to DA-REPOCH. RCODOXM/RIVAC: CYCLES 1 AND 3: Patients receive rituximab intravenously (IV) or rituxan hycela subcutaneously (SC) on day 1, cyclophosphamide IV on days 1 and 2, doxorubicin IV on day 1, vincristine IV on day 1 and 15 and methotrexate IV, over 2-4 hours on day 15. CYCLES 2 AND 4: Patients receive rituximab IV or rituan hycela SC on day 1, ifosfamide IV and etoposide IV on days 1-5, and cytarabine IV every 12 hours on days 1-2. Patients without baseline central nervous system (CNS) disease also receive methotrexate intrathecally (IT) and cytarabine IT once per cycle for 4 treatments or methotrexate IT twice per cycle for 8 treatments or alternating methotrexate IT and cytarabine IT twice per cycle for 8 treatments. Patients with baseline CNS disease also receive methotrexate IT and cytarabine IT twice weekly, methotrexate IT or alternating methotrexate IT and cytarabine IT until cerebrospinal fluid (CSF) clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. DA-REPOCH: Patients receive rituximab IV or rituxan hycela SC on day 1, etoposide IV continuously, doxorubicin IV continuously and vincristine IV continuously on days 1-4, cyclophosphamide IV on day 5, and prednisone orally (PO) twice daily (BID) on days 1-5. Patients without baseline CNS disease also receive methotrexate IT and cytarabine IT once per cycle for 4 treatments or methotrexate IT twice per cycle for 8 treatments or alternating methotrexate IT and cytarabine IT twice per cycle for 8 treatments. Patients with baseline CNS disease also receive methotrexate IT and cytarabine IT twice weekly, methotrexate IT or alternating methotrexate IT and cytarabine IT until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET), computed tomography (CT) scan, and/or magnetic resonance imaging (MRI) and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. ARM 2: Patients receive either RCODOXM/RIVAC or DA-REPOCH with glofitamab per the investigators choice. Patients over the age of 60 or with other co-morbidities are assigned to DA-REPOCH. RCODOXM/RIVAC: CYCLES 1 AND 3: Patients receive rituximab IV or rituxan hycela SC on day 1, cyclophosphamide IV on days 1 and 2, doxorubicin IV on day 1, vincristine IV on day 1 and 15 and methotrexate IV, over 2-4 hours on day 15. Patients also receive glofitamab IV, over 2-4 hours, on day 2 of cycle 3. CYCLES 2 AND 4: Patients receive rituximab IV or rituan hycela SC on day 1, ifosfamide IV and etoposide IV on days 1-5, and cytarabine IV every 12 hours on days 1-2. Patients also receive glofitamab IV, over 2-4 hours, on day 6 and 15 of cycle 2 and day 6, 22, 43 64 and 85 of cycle 4. Patients without baseline CNS disease also receive methotrexate IT and cytarabine IT once per cycle for 4 treatments or methotrexate IT twice per cycle for 8 treatments or alternating methotrexate IT and cytarabine IT twice per cycle for 8 treatments. IT treatment can not be given on the same day as glofitamab. Patients with baseline CNS disease also receive methotrexate IT and cytarabine IT twice weekly, methotrexate IT or alternating methotrexate IT and cytarabine IT until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. IT treatment can not be given on the same day as glofitamab. Patients undergo PET, CT scan, and/or MRI and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. DA-REPOCH: Patients receive rituximab IV or rituxan hycela SC on day 1, etoposide IV continuously, doxorubicin IV continuously and vincristine IV continuously on days 1-4, cyclophosphamide IV on day 5, and prednisone PO BID on days 1-5. Patients also receive glofitamab IV, over 2-4 hours on day 6 and 15 of cycle 2, day 6 of cycle 3-5 and days 6, 22 and 43 of cycle 6. Patients without baseline CNS disease also receive methotrexate IT and cytarabine IT once per cycle for 4 treatments or methotrexate IT twice per cycle for 8 treatments or alternating methotrexate IT and cytarabine IT twice per cycle for 8 treatments. IT treatment can not be given on the same day as glofitamab. Patients with baseline CNS disease also receive methotrexate IT and cytarabine IT twice weekly, methotrexate IT or alternating methotrexate IT and cytarabine IT until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. IT treatment can not be given on the same day as glofitamab. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET, CT scan, and/or MRI and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. COHORT 2: Patients are randomized to 1 of 2 arms. ARM 3: Patients receive rituximab IV or rituxan hycela SC on day 1, etoposide IV continuously, doxorubicin IV continuously and vincristine IV continuously on days 1-4, cyclophosphamide IV on day 5, and prednisone PO BID on days 1-5. Patients without baseline CNS disease may also receive methotrexate IT once per cycle for 4-6 treatments. Patients with baseline CNS disease also receive methotrexate IT twice weekly until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET, CT scan, and/or MRI and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. ARM 4: Patients receive rituximab IV or rituxan hycela SC on day 1, etoposide IV continuously, doxorubicin IV continuously and vincristine IV continuously on days 1-4, cyclophosphamide IV on day 5, and prednisone PO BID on days 1-5. Patients also receive glofitamab IV, over 2-4 hours, on day 6 and 15 of cycle 2, day 6 of cycle 3-5 and days 6, 22 and 43 of cycle 6. Patients without baseline CNS disease may also receive methotrexate IT once per cycle for 4-6 treatments. IT treatment can not be given on the same day as glofitamab. Patients with baseline CNS disease also receive methotrexate IT twice weekly until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. IT treatment can not be given on the same day as glofitamab. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET, CT scan, and/or MRI and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. COHORT 3: Patients receive obinutuzumab IV on day 1 of cycle 1, rituximab IV or rituxan hyceka SC on day 4 of cycle 1 and on day 1 of subsequent cycles, ifosfamide IV continuously on day 2, carboplatin, over 1 hour, on day 2, etoposide IV, over 2 hours, on days 1-3 and glofitamab IV, over 2-4 hours, on day 8 and 15 of cycle 1, on day 4 of cycles 2-3 and day 4 and 22 of cycle 4. Patients without baseline CNS disease may also receive methotrexate IT once per cycle for 4-6 treatments. IT treatment can not be given on the same day as glofitamab. Patients with baseline CNS disease also receive methotrexate IT twice weekly until CSF clears then weekly methotrexate IT for 4 weeks then methotrexate IT once per cycles for remaining cycles. IT treatment can not be given on the same day as glofitamab. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Responding patients may come off study any time after cycle 3 to receive transplant or chimeric antigen receptor therapy. Patients undergo PET, CT scan, and/or MRI and lumbar puncture with CSF sample collection throughout the study. Patients may undergo bone marrow biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months until 5 years.