Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma
18 Years and older, Male and Female
This randomized phase II trial studies how well obinutuzumab with or without PI3K-delta inhibitor TGR-1202, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. PI3K-delta inhibitor TGR-1202 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, 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. It is not yet known whether giving obinutuzumab with or without PI3K-delta inhibitor TGR-1202, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.
I. To compare the complete response rate at 6 cycles after randomization as defined by centrally read positron emission tomography (PET)/computed tomography (CT) (integral biomarker) of 2 targeted therapeutic regimens (obinutuzumab + PI3K-delta inhibitor TGR-1202 [TGR-1202] or obinutuzumab + lenalidomide) with obinutuzumab + cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) in patients with early relapsing or refractory follicular lymphoma.
I. To validate the prognostic association of fthe m7-FLIPI model, demonstrating that the population of follicular lymphoma patients who respond poorly to chemoimmunotherapy are enriched for having a high-risk m7-FLIPI score (integrated biomarker), and that the score is associated with progression-free survival (integrated biomarker). (Primary translational medicine)
II. To estimate the 30 month sustained complete response rate (CR30) defined by centrally read PET/CT with each of the regimens in this early relapsing or refractory follicular lymphoma population.
III. To estimate best response at 12 cycles of therapy, progression free survival, duration of response and overall survival with each of the combinations in early relapsing or refractory follicular lymphoma.
IV. To evaluate the adverse effects of each of the regimens in early relapsing or refractory follicular lymphoma.
V. To evaluate the predictive performance of non-invasive genotyping (m7-FLIPI in circulating tumor deoxyribonucleic acid [DNA]) of plasma at study entry relative to standard tumor genotyping (m7-FLIPI) of formalin-fixed paraffin-embedded tumor tissue.
VI. To evaluate the association between the detection of active lymphoma by PET-CT and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive obinutuzumab intravenously (IV) on day 1 and PI3K-delta inhibitor TGR-1202 orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive obinutuzumab IV on day 1 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive obinutuzumab IV on day 1, cyclophosphamide IV over 15 minutes on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment with obinutuzumab repeats every 21 or 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Treatment with combination chemotherapy repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Treatment Sites in Georgia
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