A Study of Duvelisib in Combination With Rituximab and Bendamustine vs Placebo in Combination With Rituximab and Bendamustine in Subjects With Previously-Treated Indolent Non-Hodgkin Lymphoma (BRAVURA)

SecuraBio

Overview

This study will evaluate the efficacy and safety of duvelisib in combination with bendamustine and rituximab (DBR) vs placebo in combination with bendamustine and rituximab (PBR) in subjects with previously-treated indolent non-Hodgkin lymphoma (iNHL).

Study IPI-145-22 is an international, multicenter, randomized, double-blind, placebo-controlled, two-arm Phase 3 study designed to evaluate efficacy and safety of DBR vs PBR in subjects with previously-treated iNHL (including follicular lymphoma \[FL\], small lymphocytic lymphoma \[SLL\] and marginal zone lymphoma \[MZL\]). Approximately 600 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 on Day 1 of Cycles 1-6 and 90 mg/m2 of bendamustine given on Day 1 and Day 2 of Cycles 1-6. Subjects will receive duvelisib until disease progression or unacceptable toxicity.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Indolent Non-Hodgkin's Lymphoma Follicular Lymphoma Small Lymphocytic Lymphoma Marginal Zone Lymphoma

Interventions

DuvelisibDRUG

Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles

PlaceboDRUG

Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles

RituximabDRUG

IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of iNHL with one of the following histologic sub-types and grade: * Follicular lymphoma (FL)Grade 1, 2, or 3a * Small lymphocytic lymphoma (SLL) * Marginal zone lymphoma (MZL)( splenic, nodal, or extranodal) * Have received the following systemic treatments for iNHL: * an anti-CD20 antibody; and * chemotherapy * At least 1 measurable disease lesion \> 1.5 cm in at least one dimension by computed tomography (CT)/CT-PET or magnetic resonance imaging (MRI) * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (corresponds to Karnofsky Performance Status \[(KPS) ≥60%\]) Exclusion Criteria: * Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL * Refractory to bendamustine + rituximab therapy or single-agent bendamustine 120 mg/m2, with refractory defined as: \- Progression of disease while receiving or within 6 months of completing treatment * Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs * Received prior allogeneic transplant * Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor * Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). * History of tuberculosis treatment within the two years prior to randomization * History of chronic liver disease, veno-occlusive disease, or alcohol abuse * Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \> 20 mg of prednisone (or equivalent) daily (QD) * Ongoing treatment for systemic bacterial, fungal, or viral infection at screening * Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening * Concurrent active malignancy other than adequately treated non-melanoma skin cancer or lentigo maligna without evidence of invasive disease or adequately treated cervical carcinoma in situ without evidence of disease * History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening * History of progressive multifocal leukoencephalopathy

Locations (7)

Unnamed facility

Plainville, Connecticut, United States

Unnamed facility

Plantation, Florida, United States

Unnamed facility

Thomasville, Georgia, United States

Unnamed facility

East Setauket, New York, United States

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Time frame: From date of enrollment until the date of first documentation of progression or date of death from any cause, whatever came first, assessed up to 78 months

Secondary Outcomes

Complete Response (CRR)

Time frame: Every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.

Overall Response Rate (ORR)

Overall Survival (OS)

Time frame: Every 6 months for up to 5 years from date of randomization

Duration of Response (DOR)

Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)

Time frame: Continuous from informed consent until 30 days from last dose

Pharmacokinetics (PK)

Evaluate the Duvelisib concentration in plasma sample.

Time frame: Cycle 1 and Cycle 2 (each cycle is 28 days)

Pharmacokinetics (PK)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.