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)

Sponsor

SecuraBio (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02576275

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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).

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

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (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

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Nov 1, 2016

Actual Study Completion Date :

Nov 1, 2016

Arms and Interventions

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: 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

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: 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

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) [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) [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) [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) [Every 6 months for up to 5 years from date of randomization]
Duration of Response (DOR) [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) [Continuous from informed consent until 30 days from last dose]
Pharmacokinetics (PK) [Cycle 1 and Cycle 2 (each cycle is 28 days)]
Evaluate the Duvelisib concentration in plasma sample.
Pharmacokinetics (PK) [Cycle 1 and Cycle 2 (each cycle is 28 days)]
Evaluate IPI-656 (metabolite) concentration in plasma sample.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	City	State	Country	Postal Code
1	Plainville	Connecticut	United States	06062
2	Plantation	Florida	United States	33322
3	Thomasville	Georgia	United States	31792
4	East Setauket	New York	United States	11733-3456
5	Cookeville	Tennessee	United States	38501
6	Knoxville	Tennessee	United States	37909
7	Spokane	Washington	United States	99208