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)

NCT02576275 | Withdrawn Phase 3 DMC

• 1 other identifier: IPI-145-22
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

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).

Conditions

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

Keywords

Phase 3; iNHL; Follicular Lymphoma; FL; PI3K; Small Lymphocytic Lymphoma; SLL; Marginal Zone Lymphoma; MZL

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  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 (7)

• Complete Response (CRR)

  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)

  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 Survival (OS)

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

• Duration of Response (DOR)

  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.

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

  Continuous from informed consent until 30 days from last dose

Study Arms (2)

Duvelisib + Rituximab + Bendamustine

EXPERIMENTAL

Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Bendamustine is administered as an intravenous (IV) infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg. Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.

Drug: Duvelisib; Drug: Rituximab; Drug: Bendamustine

Placebo + Rituximab + Bendamustine

PLACEBO COMPARATOR

Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules of duvelisib. Bendamustine is administered as an IV infusion and is supplied for injection in single-use vials at two strengths, 25 mg and 100 mg. Rituximab is administered as an IV infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.

Drug: Placebo; Drug: Rituximab; Drug: Bendamustine

Interventions

Duvelisib DRUG

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

Also known as: IPI-145

Duvelisib + Rituximab + Bendamustine

Placebo DRUG

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

Placebo + Rituximab + Bendamustine

Rituximab DRUG

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

Also known as: Rituxan, MabThera

Duvelisib + Rituximab + Bendamustine; Placebo + Rituximab + Bendamustine

Bendamustine DRUG

IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6.

Also known as: Treanda, Levact

Duvelisib + Rituximab + Bendamustine; Placebo + Rituximab + Bendamustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[(KPS) ≥60%\])

You may not qualify if:

• 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

Sponsors & Collaborators

• SecuraBio: lead

Study Sites (7)

Unknown Facility

Plainville, Connecticut, 06062, United States

Location

Unknown Facility

Plantation, Florida, 33322, United States

Location

Unknown Facility

Thomasville, Georgia, 31792, United States

Location

Unknown Facility

East Setauket, New York, 11733-3456, United States

Location

Unknown Facility

Cookeville, Tennessee, 38501, United States

Location

Unknown Facility

Knoxville, Tennessee, 37909, United States

Location

Unknown Facility

Spokane, Washington, 99208, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

duvelisib; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 15, 2015
• Study Start: December 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 17, 2021

Record last verified: 2021-03

Locations

US (7)