Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma

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.

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