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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)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.
ClinicalTrials.gov Identifier:
NCT02576275
First received: October 7, 2015
Last updated: February 21, 2017
Last verified: June 2016
  Purpose
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).

Condition Intervention Phase
Indolent Non-Hodgkin's Lymphoma
Follicular Lymphoma
Small Lymphocytic Lymphoma
Marginal Zone Lymphoma
Drug: Duvelisib
Drug: Placebo
Drug: Rituximab
Drug: Bendamustine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Verastem, Inc.:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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) [ 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 Survival (OS) [ Time Frame: 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. ]
  • 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) [ Time Frame: Cycle 1 and Cycle 2 (each cycle is 28 days) ]
    Evaluate the Duvelisib concentration in plasma sample.

  • Pharmacokinetics (PK) [ Time Frame: Cycle 1 and Cycle 2 (each cycle is 28 days) ]
    Evaluate IPI-656 (metabolite) concentration in plasma sample.


Enrollment: 0
Study Start Date: December 2015
Study Completion Date: November 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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: Placebo
Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02576275

Locations
United States, Connecticut
Plainville, Connecticut, United States, 06062
United States, Florida
Plantation, Florida, United States, 33322
United States, Georgia
Thomasville, Georgia, United States, 31792
United States, New York
East Setauket, New York, United States, 11733-3456
United States, Tennessee
Cookeville, Tennessee, United States, 38501
Knoxville, Tennessee, United States, 37909
United States, Washington
Spokane, Washington, United States, 99208
Sponsors and Collaborators
Verastem, Inc.
Investigators
Study Chair: Hagop Youssoufian, MD Verastem, Inc.
  More Information

Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT02576275     History of Changes
Other Study ID Numbers: IPI-145-22
Study First Received: October 7, 2015
Last Updated: February 21, 2017

Keywords provided by Verastem, Inc.:
Phase 3
iNHL
Follicular Lymphoma
FL
PI3K
Small Lymphocytic Lymphoma
SLL
Marginal Zone Lymphoma
MZL

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 28, 2017