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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)

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ClinicalTrials.gov Identifier: NCT02576275
Recruitment Status : Withdrawn (The scope of the program has been reduced to focus resources on studies which can potentially enable the registration of duvelisib.)
First Posted : October 15, 2015
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.

Tracking Information
First Submitted Date  ICMJE October 7, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date October 16, 2018
Study Start Date  ICMJE December 2015
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Indolent Non-Hodgkin's Lymphoma
  • Follicular Lymphoma
  • Small Lymphocytic Lymphoma
  • Marginal Zone Lymphoma
Intervention  ICMJE
  • Drug: Duvelisib
    Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles
    Other Name: IPI-145
  • 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
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Duvelisib
    • Drug: Rituximab
    • Drug: Bendamustine
  • 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.

    Interventions:
    • Drug: Placebo
    • Drug: Rituximab
    • Drug: Bendamustine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 29, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2015)
600
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02576275
Other Study ID Numbers  ICMJE IPI-145-22
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Verastem, Inc.
Study Sponsor  ICMJE Verastem, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Hagop Youssoufian, MD Verastem, Inc.
PRS Account Verastem, Inc.
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP