Follicular Lymphoma, Indolent Non-Hodgkin's Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
Phase 3, iNHL, Follicular Lymphoma, FL, PI3K, Small Lymphocytic Lymphoma, SLL, Marginal Zone Lymphoma, MZL
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.
Interventions
DRUGDuvelisib
Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles
DRUGPlacebo
Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles
DRUGRituximab
IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6.
DRUGBendamustine
IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6.
Sponsors
SecuraBio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. | — |
| 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. |
| 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. | — |
Countries
United States
Outcome results
None listed