study of duvelisib in combination with rituximab vs rituximab in subjects with previously treated follicular lymphoma

Conditions: Follicular Lymphoma

Summary: a study to evaluate the safety and efficacy of duvelisib administered in combination with rituximab vs placebo in combination with rituximab in patients with previously treated cd20-positive follicular lymphoma who are not suitable candidates for chemotherapy.

study ipi-145-08 is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study designed to evaluate the efficacy and safety of duvelisib in combination with rituximab vs placebo in combination with rituximab in subjects with previously treated cd20-positive follicular lymphoma. approximately 400 subjects will receive 25 mg of duvelisib or placebo, orally bid for 28 day continuous cycles, in combination with 375 mg/m2 of rituximab given once weekly for 4 weeks during cycle 1 and then once on day 1 of cycles 4, 6, 8, and 10. patients will remain on treatment for up to 27 cycles and may continue treatment if clinical benefit is observed.

Eligibility criteria:
inclusion criteria: * diagnosis of cd20-positive fl: * histology grades 1, 2 or 3a * biopsy-confirmed histopathological diagnosis of fl. biopsy specimen should be obtained ≤2 years prior to randomization, unless medically contraindicated * cd20 immunophenotyping performed ≤2 years prior to randomization * first or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent * patients in first relapse must be chemoresistant or intolerant to chemotherapy * no response or disease progression ≤ 24 months from start of last previous therapy * at least 1 measurable disease lesion \>1.5 cm in at least one diameter by ct/ct-pet or magnetic resonance imaging (mri) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression exclusion criteria: * clinical evidence of other indolent forms of lymphoma (e.g., marginal zone lymphoma \[mzl\], small lymphocytic lymphoma \[sll\]) * transformation to a more aggressive subtype of lymphoma or grade 3b fl * refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction * intolerance to rituximab or severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies * prior allogeneic hematopoietic stem cell transplant (hsct) * known central nervous system (cns) lymphoma; subjects with symptoms of cns disease must have a negative ct scan and negative diagnostic lumbar puncture * prior treatment with a pi3k inhibitor or btk inhibitor * history of tuberculosis within the preceding two years * ongoing systemic bacterial, fungal, or viral infections at randomization (defined as requiring iv antimicrobial, antifungal or antiviral agents) * subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other i/e criteria are met * prior, current, or chronic hepatitis b or hepatitis c infection, positive result for hepatitis b surface antigen (hbsag) or hepatitis b core antibody (hbcab) or hepatitis c virus antibodies (hcv ab) * history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months

Keywords: phase 3, follicular lymphoma, fl, pi3k