Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma

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.

Inclusion Criteria:
• Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on PET/CT; patients that have involvement with large cell lymphoma are not eligible
• Patients must not have clinical evidence of central nervous system involvement by lymphoma
• Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing first line bendamustine-containing chemoimmunotherapy, as measured from the last dose of bendamustine; relapsed patients must not have received any intervening chemotherapy; patients must have received at least 3 cycles of bendamustine as first line therapy; (Note that no minimum dose of bendamustine is required); patients who additionally received any maintenance anti-CD-20 antibody based therapy or consolidative radioimmunotherapy within 2 years of the last dose of the bendamustine therapy are eligible; involved field or involved site radiation is not considered a line of therapy; patients who previously received anthracycline based therapy are excluded
• Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide
• All patients must have a Zubrod performance status of 0, 1 or 2
• Patients must have adequate renal function
• No prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for three years
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test; further, they must either commit to complete abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control

Exclusion Criteria:
• Patients must be able to discontinue CYP2C9 substrates with a narrow therapeutic index, if randomized to TGR-1202; patients must discontinue such agents at least 1 week or 5 half-lives prior to beginning protocol therapy (whichever is longer)
Phase II
Gary Goodman, M.D.
Sage Therapeutics
Neysa Dagostino

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.