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The scope of the program has been reduced to focus resources on studies which can potentially enable the registration of duvelisib.
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Duvelisib + Rituximab + Bendamustine | Experimental | 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 + Rituximab + Bendamustine | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Duvelisib | Drug | Duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles |
|
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Diagnosis of iNHL with one of the following histologic sub-types and grade:
Have received the following systemic treatments for iNHL:
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
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| Name | Affiliation | Role |
|---|---|---|
| Hagop Youssoufian, MD | Verastem, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Plainville | Connecticut | 06062 | United States | |||
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| Placebo | Drug | Matching placebo (25 mg BID) administered orally in 28-day continuous treatment cycles |
|
| Rituximab | Drug | IV infusion of rituximab (375 mg/m2) on Day 1 of Cycles 1-6. |
|
|
| Bendamustine | Drug | IV infusion of bendamustine (90 mg/m2) on Day 1 and Day 2 of Cycles 1-6. |
|
|
| 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) | Evaluate the Duvelisib concentration in plasma sample. | Cycle 1 and Cycle 2 (each cycle is 28 days) |
| Pharmacokinetics (PK) | Evaluate IPI-656 (metabolite) concentration in plasma sample. | Cycle 1 and Cycle 2 (each cycle is 28 days) |
| Plantation |
| Florida |
| 33322 |
| United States |
| Thomasville | Georgia | 31792 | United States |
| East Setauket | New York | 11733-3456 | United States |
| Cookeville | Tennessee | 38501 | United States |
| Knoxville | Tennessee | 37909 | United States |
| Spokane | Washington | 99208 | United States |
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016393 | Lymphoma, B-Cell |
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| ID | Term |
|---|---|
| C586691 | duvelisib |
| D000069283 | Rituximab |
| D000069461 | Bendamustine Hydrochloride |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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