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

Phase 3

Terminated

• Conditions: Follicular Lymphoma
• Interventions: Drug: Duvelisib; Drug: Placebo; Drug: Rituximab

• Registration Number: NCT02204982
• Lead Sponsor: SecuraBio

Brief 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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2014-07-25
• Study First Submitted QC: 2014-07-29
• Study First Posted: 2014-07-31
• Study Start: 2014-09
• Primary Completion: 2016-12
• Study Completion: 2017-03
• Disposition First Submitted: 2018-05-02
• Disposition First Submitted QC: 2018-05-02
• Disposition First Posted: 2018-05-04
• Results First Submitted: 2018-10-23
• Results First Submitted QC: 2018-12-10
• Results First Posted: 2019-01-03
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-07
• Last Update Posted: 2023-09-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Duvelisib + Rituximab	Duvelisib	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.
Duvelisib + Rituximab	Rituximab	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.
Placebo + Rituximab	Placebo	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.
Placebo + Rituximab	Rituximab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Until disease progression, for up to 5 years from randomization