Clinical trial NCT02576275: 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
Overall status: WITHDRAWN
Phase: PHASE3
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
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2015-10-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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:
measure: Complete Response (CRR)
timeFrame: 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.
measure: Overall Response Rate (ORR)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: Every 6 months for up to 5 years from date of randomization
measure: Duration of Response (DOR)
timeFrame: 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.
measure: Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)
timeFrame: Continuous from informed consent until 30 days from last dose
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1 and Cycle 2 (each cycle is 28 days)
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1 and Cycle 2 (each cycle is 28 days)
Other outcomes:
Locations:
city: Plainville
country: United States
state: Connecticut
city: Plantation
country: United States
state: Florida
city: Thomasville
country: United States
state: Georgia
city: East Setauket
country: United States
state: New York
city: Cookeville
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Spokane
country: United States
state: Washington
Study officials:
affiliation: Verastem, Inc.
name: Hagop Youssoufian, MD
role: STUDY_CHAIR
References: