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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Duvelisib
* Drug: Placebo
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duvelisib + Rituximab<br>Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. | Drug: Duvelisib<br>* PI3K Inhibitor<br>* Other names: Copiktra, IPI-145;Drug: Rituximab<br>* IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.<br>* Other names: MabThera;|
| Placebo Comparator: Placebo + Rituximab<br>Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. | Drug: Placebo<br>* Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles.<br>Drug: Rituximab<br>* IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.<br>* Other names: MabThera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed. | Until disease progression, for up to 5 years from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) |  | Until disease progression, for up to 5 years from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 3, Follicular Lymphoma, FL, PI3K