A Study of Duvelisib in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

Study Overview
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Brief Summary
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This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of PI3K-δ,γ, in patients with relapsed/refractory Peripheral T-cell Lymphoma (PTCL).

Detailed Description
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The study has 2 phases, a Dose Optimization Phase and an Expansion Phase. In the Dose Optimization Phase, patients will be randomly assigned to 1 of 2 study cohorts, as follows: Cohort 1: Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-patient basis to 50 mg and then 75 mg, based on the patient's response to and tolerance of therapy, in 28-day cycles. Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles. A total of 20 patients will be enrolled in the Dose Optimization Phase, with 10 patients per cohort. Based on the safety and activity data obtained in the Dose Optimization Phase of the study, the Expansion Phase dose of Duvelisib will be determined. In the Expansion Phase, approximately 100-130 patients may be enrolled and will receive Duvelisib dose in 28-day cycles as determined in Dose Optimization Phase.

Official Title
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A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety of Duvelisib in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Duvelisib
* Drug: Duvelisib
* Drug: Duvelisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age Diagnosis of one of the following histologic subtypes of PTCL, pathologically confirmed, as defined by the World Health Organization: Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS); Angioimmunoblastic T-cell lymphomas (AITL); Anaplastic large cell lymphoma (ALCL); or Natural-killer/T-cell lymphoma (NKTL) Received at least 2 cycles of one standard regimen for newly diagnosed advanced PTCL, and one of the following: failed to achieve at least a PR after 2 or more cycles of standard therapy; failed to achieve a CR after completion of standard therapy; and/or persistent or progressive disease after an initial response For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin Measurable disease as defined by Lugano for PTCL, that is, at least 1 measurable disease lesion > 1.5 cm in at least one dimension by conventional techniques (18FDG-PET-CT, CT with contrast, MRI) Exclusion Criteria: Primary leukemic PTCL subtypes (that is, T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma and aggressive NK-cell leukemia) or transformed mycosis fungoides Received prior allogeneic transplant Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor Known central nervous system involvement by PTCL Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) once daily (QD) Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening Known hypersensitivity to duvelisib and/or its excipients

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Optimization Phase: Cohort 1<br>Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-patient basis to 50 mg and then 75 mg, based on the patient's response to and tolerance of therapy, in 28-day cycles. | Drug: Duvelisib<br>* Duvelisib PO 25 mg BID or 50 mg BID or 75 mg BID in 28-day cycles.<br>|
| Experimental: Dose Optimization Phase: Cohort 2<br>Duvelisib 75 mg PO BID, administered in 28-day cycles. | Drug: Duvelisib<br>* Duvelisib PO 75 mg BID in 28-day cycles.<br>|
| Experimental: Expansion Phase<br>Duvelisib PO BID at a starting dose of 75 mg for the first 2 cycles, followed by a mandatory reduction to 25 mg BID thereafter for those patients with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase). | Drug: Duvelisib<br>* Duvelisib PO BID in 28-day cycles (dose determined in Optimization Phase)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Best response of CR or PR | From start of treatment to first documented response, assessed up to 2 cycles (58 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse events (TEAEs) as Assessed by CTCAE v4.0 |  | From start of treatment to end of treatment plus 30 days; 7 months | 
| Duration of Response (DOR) |  | Time from the first documentation of response to first documentation of progressive disease or death due to any cause, 6 months | 
| Progression-free Survival (PFS) |  | Time from start of treatment to first documentation of progression or date of death from any cause, whichever came first, 4 months | 
| Disease Control Rate (DCR) |  | Greater than or equal to 8 weeks | 
| Overall Survival (OS) |  | From start of treatment until death, 6 months | 
| Plasma Concentration of Duvelisib and Metabolites |  | Days 1, 8, and 15 (Predose, up to 6 hours post dose) of Cycles 1, 2, 3, and 5 (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, T-cell Lymphoma, Relapse, Refractory, PI3K-δ,γ