NCI Community Oncology Research Program - Protocol Summary
SWOG S1608 - "Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma"
The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please contact NCORP-KC for complete protocol information.
Lymphoma Clinical Trial
CANCER TYPE: Non-Hodgkin's
RESEARCH BASE: SWOG
NCT NUMBER: NCT03269669
HIPPA FORM: DOWNLOAD HIPPA FORM
Consent Form: VIEW CONSENT FORM
UPDATED ON 07/27/2018 (16:05:02)
Relapsing or refractory follicular lymphoma, grade I, II, IIIa, Obinutuzumab + TGR-1202 or Lenalidomide or CHOP
Treatment (Supplied drug: Lenalidomide, Obinutuzumab and TGR-1202)
Obinutuzumab 1000mg, IV, day 1, x 12 cycles
TGR-1202 800mg, PO, Daily, x 12 cycles
1 cycle = 28 days
Obinutuzumab 1000mg, IV, day 1, x 12 cycles
Lenalidomide 20mg, PO, days 1-21, x 12 cycles
1 cycle = 28 days
Obinutuzumab 1000mg, IV, day 1, x12 cycles
Cyclophosphamide 750mg/m2, IV, day 1, x 6 cycles
Doxorubicin 50mg/m2, IV, day 1, x 6 cycles
Vincristine 1.4mg/m2, IV, day 1, x 6 cycles
Prednisone 100mg, PO, days 1-5, x 6 cycles
Cycles 1-6: 1 cycle = 21 days
Cycles 7-12: 1 cycle = 28 days
- Patients must have follicular lymphoma (Grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable 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, since the proposed treatment strategies are not designed to address CNS involvement adequately. If performed, any laboratory or radiographic tests performed to assess CNS involvement must be negative.
- Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration.
- Patients must have bone marrow biopsy performed within 42 days prior to registration.
- Patients must meet all the following:
- Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing first line bendamustine-containing chemoimmunotherapy (including an anti-CD20 monoclonal antibody), 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.
- Examples of eligible 1st line treatment regimens (note this list is not all inclusive):
- Bendamustine rituximab x 4 cycles
- Bendamustine bortezomib rituximab x 6 cycles followed by rituximab maintenance
- Bendamustine obinutuzumab x 3 cycles
- For all forms of systemic therapy, patients must have completed therapy at least 21 days prior to registration. Patients must have completed any radioimmunotherapy at least 84 days prior to registration. Patients must have recovered from all treatment related toxicities from these therapies prior to registration.
- Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide.
- Patients must have blood and tissue specimens collected prior to registration and submitted for translational medicine as outlined in Section 15.1. See Section 15.1e for information regarding pre-ordering of specimen kits. Note that patients without adequate diagnostic specimens will not be eligible. With patient consent, residuals from the mandatory submission will be banked for future research.
- Patients must be ≥ 18 years of age.
- All patients must have a Zubrod performance status of 0, 1 or 2 (see Section 10.4).
- Patients must have adequate bone marrow function as evidenced by ANC ≥ 1,500/mcL and platelets ≥ 75,000/mcL within 28 days prior to registration.
- Patients must have adequate renal function as documented by a calculated creatinine clearance ≥ 60 mL/min, within 28 days prior to registration.
- Patients must have adequate hepatic function obtained within 28 days prior to registration and documented by all of the following:
- Total bilirubin ≤ 1.5 x IULN (≤ 5 x IULN if secondary to lymphoma, Gilbert’s syndrome, or medication related [e.g., indinavir, tenofovir, atazanavir])
- Direct bilirubin ≤ 1.5 x IUL10N (≤ 5 x IULN if secondary to lymphoma)
- AST and ALT ≤ 2.5 x IULN (≤ 5 x IULN secondary to lymphoma)
- Patients must have an echocardiogram (ECHO) or MUGA scan within 42 days prior to registration with a cardiac ejection fraction ≥ 45%.
- Patients with Hepatitis B Virus infection must have undetectable HBV on suppressive therapy and no evidence of HBV-related hepatic damage. Patients with Hepatitis C virus infection are eligible if complete eradication therapy has been successfully completed, and there is no detectable HVC or related hepatic damage.
- Patients with known HIV infection are eligible if they meet all of the following criteria in addition to the other protocol eligibility criteria:
- Patient must have no history of AIDS-related complications, other than a history of low CD4+ T-cell count (< 200/mm3) prior to initiation of combination antiretroviral therapy. On study CD4+ T-cell count may not be informative due to leukemia and should not be used as an exclusion criterion if low.
- Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the leukemia.
- Patient must have serum HIV viral load of < 200 copies/mm3
- Patient must be on combination antiretroviral therapy with minimal pharmacokinetic interactions with study therapy and minimal overlapping clinical toxicity with protocol therapy. (Recommend a regimen of the integrase inhibitor dolutegravir combined with either disoproxil fumarate/emtricitabine or dolutegravir combined with tenofovir alafenamide/emtricitabine.)
- Protease inhibitors and once daily formulations containing cobicistat are NOT allowed due to potential pharmacokinetic interactions with leukemia therapy.
- Stavudine and zidovudine are NOT allowed because of overlapping toxicity with protocol therapy.
- Patients must be able and willing to receive prophylaxis with daily aspirin, low molecular weight heparin, factor X inhibitors or Warfarin if randomized to lenalidomide. Patients must also be willing to receive pneumocysitis jirovecii prophylaxis with sulfamethoxazole/trimethoprim, dapsone, atovaquone or inhaled pentamadine, in the event that they are randomized to TGR-1202. Patients unable or unwilling to take any listed prophylaxis are NOT eligible.
- Patients must be able to discontinue CYP2C9 substrates with a narrow therapeutic index (e.g. warfarin, phenytoin), 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). A list of 2C9 substrates is available at http://medicine.iupui.edu/clinpharm/ddis/main-table/. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference.
- No second 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.
- Patients must have a complete history and physical examination within 28 days prior to registration.
- Patients must have the following components of Follicular Lymphoma International Prognostic Index (FLIPI) available from diagnosis, and collected again at time of registration:
- Number of nodal groups involved (see Appendix 18.7)
- Serum or plasma hemoglobin
- Ann Arbor Stage
- Additionally, patients must have beta-2-microglobulin collected at time of registration.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide. Further, they must either commit to complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g., calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, while taking lenalidomide, during dose interruptions, and for at least 28 days after the last dose of lenalidomide.