A Study of Duvelisib in Combination With Rituximab or Obinutuzumab in Subjects With Previously Untreated CD20+ Follicular Lymphoma (CONTEMPO)

Study Overview
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Brief Summary
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A Two-arm, Phase 1b/2 Study of duvelisib Administered in Combination with Rituximab or Obinutuzumab in Subjects with Previously Untreated CD20+ Follicular Lymphoma.

Detailed Description
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This is a two-arm, open-label, Phase 1b/2 trial designed to evaluate the safety and efficacy of duvelisib in combination with rituximab and duvelisib in combination with obinutuzumab in subjects with previously untreated CD20+ FL. The study will be conducted in two parts, a Safety Lead-in (Part 1) followed by a randomized, 2-Stage Design in Part 2. Each treatment arm will be assessed independently for dose limiting toxicity (DLT) within Part 1.

Official Title
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A Two-arm, Phase 1b/2 Study of Duvelisib Administered in Combination With Rituximab or Obinutuzumab in Subjects With Previously Untreated CD20+ Follicular Lymphoma (CONTEMPO)

Conditions
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CD20+ Follicular Lymphoma

Intervention / Treatment
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* Drug: Duvelisib
* Drug: Rituximab
* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CD20+, follicular lymphoma that has not been treated CD20-immunophenotyping of tumor to document B-cell follicular lymphoma Stage II disease with bulky disease (≥ 7cm lesion), Stage III, or Stage IV disease Disease that requires treatment based on the Investigator's opinion (e.g., meets GELF criteria) At least one measurable lesion that is > 1.5 cm in at least one dimension Eastern Cooperative Oncology Group (ECOG) performance status <=2 (corresponds to Karnofsky Performance Status [KPS] >=60%) Exclusion Criteria: Received systemic treatment for lymphoma such as chemotherapy, immunotherapy, radiotherapy, investigational agents, or radioimmunotherapy. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B follicular lymphoma Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs Prior allogeneic hematopoietic stem cell transplant Prior, current or chronic hepatitis B or hepatitis C infection Human immunodeficiency virus (HIV) infection or Human T Cell Lymphotropic Virus 1 (HTLV-1) infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duvelisib and Rituximab<br>Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Duvelisib will be administered orally, twice daily, in 28-day cycles. Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Cycle 1 (28 day cycles); days 1, 8, 15 and 22. Thereafter, infusions will occur on Day 1 of the even cycles treatment; Cycles 4-26. | Drug: Duvelisib<br>* PI3K Inhibitor<br>* Other names: Copiktra, IPI-145;Drug: Rituximab<br>* monoclonal antibody<br>* Other names: Rituxan/MabThera®;|
| Experimental: Duvelisib and Obinutuzumab<br>Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Duvelisib will be administered orally, twice daily, in 28-day cycles. Obinutuzumab 1000 mg will be administered intravenously (IV) beginning at Cycle 1 (28 day cycles); days 1, 8, 15 and 22. Thereafter, infusions will occur on Day 1 of the even cycles treatment; Cycles 4-26. | Drug: Duvelisib<br>* PI3K Inhibitor<br>* Other names: Copiktra, IPI-145;Drug: Obinutuzumab<br>* monoclonal antibody<br>* Other names: GAZYVA/GAZYVARO™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Dose Limiting Toxicities (DLTs) - Part 1 |  | 28 days from first dose of study treatment | 
| Complete Response Rate (CRR)- Part 2 |  | Up to 2 years from the first dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | Composite measure of safety, as indicated by Treatment-emergent adverse events (TEAEs) and changes in safety laboratory values. TEAEs assessed as >=Grade 3. | Up to 30 days after the last dose of study treatment | 
| Overall Response Rate (ORR) |  | Up to 2 years from the first dose of study treatment | 
| Duration of Response (DOR) | The median DOR was non-estimable. | Up to 2 years from the first dose of study treatment | 
| Overall Survival (OS) |  | Up to 2 years from the first dose of study treatment | 
| Pharmacokinetic (PK): Plasma Concentrations of Duvelisib and IPI-656 (Metabolite) | Plasma concentrations of Duvelisib and IPI-656 (metabolite) | Every 4 weeks for 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicular Lymphoma, Previously Untreated