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)

March 15, 2021 updated by: SecuraBio

A Phase 3, Randomized, Double-blind Study of Duvelisib Administered in Combination With Rituximab and Bendamustine vs Placebo Administered in Combination With Rituximab and Bendamustine in Subjects With Previously-Treated Indolent Non-Hodgkin Lymphoma

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 Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • Plainville, Connecticut, United States, 06062
    • Florida
      • Plantation, Florida, United States, 33322
    • Georgia
      • Thomasville, Georgia, United States, 31792
    • New York
      • East Setauket, New York, United States, 11733-3456
    • Tennessee
      • Cookeville, Tennessee, United States, 38501
      • Knoxville, Tennessee, United States, 37909
    • Washington
      • Spokane, Washington, United States, 99208

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Duvelisib + Rituximab + Bendamustine

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
Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles
Other Names:
  • IPI-145
Drug: Rituximab
IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6.
Other Names:
  • Rituxan
  • MabThera
Drug: Bendamustine
IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6.
Other Names:
  • Treanda
  • Levact
PLACEBO_COMPARATOR: Placebo + Rituximab + Bendamustine

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: Rituximab
IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6.
Other Names:
  • Rituxan
  • MabThera
Drug: Bendamustine
IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6.
Other Names:
  • Treanda
  • Levact
Drug: Placebo
Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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)
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.
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)
Time Frame: Every 6 months for up to 5 years from date of randomization
Every 6 months for up to 5 years from date of randomization
Duration of Response (DOR)
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.
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)
Time Frame: Continuous from informed consent until 30 days from last dose
Continuous from informed consent until 30 days from last dose
Pharmacokinetics (PK)
Time Frame: Cycle 1 and Cycle 2 (each cycle is 28 days)
Evaluate the Duvelisib concentration in plasma sample.
Cycle 1 and Cycle 2 (each cycle is 28 days)
Pharmacokinetics (PK)
Time Frame: Cycle 1 and Cycle 2 (each cycle is 28 days)
Evaluate IPI-656 (metabolite) concentration in plasma sample.
Cycle 1 and Cycle 2 (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SecuraBio

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (ACTUAL)

November 1, 2016

Study Completion (ACTUAL)

November 1, 2016

Study Registration Dates

First Submitted

October 7, 2015

First Submitted That Met QC Criteria

October 12, 2015

First Posted (ESTIMATE)

October 15, 2015

Study Record Updates

Last Update Posted (ACTUAL)

March 17, 2021

Last Update Submitted That Met QC Criteria

March 15, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IPI-145-22

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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