Back to resultsA 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)
Primary Purpose
Indolent Non-Hodgkin's Lymphoma, Follicular Lymphoma, Small Lymphocytic Lymphoma
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Duvelisib
Placebo
Rituximab
Bendamustine
Sponsored by
About this trial
This is an interventional treatment trial for Indolent Non-Hodgkin's Lymphoma focused on measuring Phase 3, iNHL, Follicular Lymphoma, FL, PI3K, Small Lymphocytic Lymphoma, SLL, Marginal Zone Lymphoma, MZL
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Duvelisib + Rituximab + Bendamustine
Placebo + Rituximab + Bendamustine
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
Secondary Outcome Measures
Complete Response (CRR)
Overall Response Rate (ORR)
Overall Survival (OS)
Duration of Response (DOR)
Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)
Pharmacokinetics (PK)
Evaluate the Duvelisib concentration in plasma sample.
Pharmacokinetics (PK)
Evaluate IPI-656 (metabolite) concentration in plasma sample.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02576275
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
The scope of the program has been reduced to focus resources on studies which can potentially enable the registration of duvelisib.
Study Start Date
December 2015 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SecuraBio
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Duvelisib + Rituximab + Bendamustine
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + Rituximab + Bendamustine
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Duvelisib
Other Intervention Name(s)
IPI-145
Intervention Description
Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, MabThera
Intervention Description
IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda, Levact
Intervention Description
IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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.
Title
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.
Title
Overall Survival (OS)
Time Frame
Every 6 months for up to 5 years from date of randomization
Title
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.
Title
Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)
Time Frame
Continuous from informed consent until 30 days from last dose
Title
Pharmacokinetics (PK)
Description
Evaluate the Duvelisib concentration in plasma sample.
Time Frame
Cycle 1 and Cycle 2 (each cycle is 28 days)
Title
Pharmacokinetics (PK)
Description
Evaluate IPI-656 (metabolite) concentration in plasma sample.
Time Frame
Cycle 1 and Cycle 2 (each cycle is 28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hagop Youssoufian, MD
Organizational Affiliation
Verastem, Inc.
Official's Role
Study Chair
Facility Information:
City
Plainville
State/Province
Connecticut
ZIP/Postal Code
06062
Country
United States
City
Plantation
State/Province
Florida
ZIP/Postal Code
33322
Country
United States
City
Thomasville
State/Province
Georgia
ZIP/Postal Code
31792
Country
United States
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733-3456
Country
United States
City
Cookeville
State/Province
Tennessee
ZIP/Postal Code
38501
Country
United States
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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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