A Study of Duvelisib in Participants With Refractory Indolent Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This was a Phase 2 clinical trial to evaluate the safety and efficacy of duvelisib as a monotherapy in participants with indolent non-Hodgkin lymphoma (iNHL) (follicular lymphoma [FL], marginal zone lymphoma, or small lymphocytic lymphoma) that was refractory to rituximab and to either chemotherapy or radioimmunotherapy (RIT).

Detailed Description
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This was an open-label, single-arm safety and efficacy study of duvelisib administered orally to participants who had been diagnosed with iNHL whose disease was refractory to rituximab and to either chemotherapy or RIT. Approximately 120 participants received 25 milligrams of duvelisib twice daily over the course of 28-day treatment cycles for up to 13 cycles. After completing 13 treatment cycles of duvelisib, participants continued to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 13 cycles, participants must have had evidence of response (complete response [CR] or partial response [PR]) or stable disease according to the International Working Group criteria by the end of Cycle 13.

Official Title
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A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma

Conditions
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Indolent Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Duvelisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who had been diagnosed with iNHL that had progressed. Participants must have exhibited lack of CR or progressive disease (PR) or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT. Participants must have had rituximab-refractory disease, defined as lack of CR or PR or PD within 6 months of last dose. Measurable disease with a lymph node or tumor mass ≥1.5 centimeters in at least one dimension by computed tomography (CT), positron emission tomography/CT or magnetic resonance imaging. Adequate renal and hepatic function. Exclusion Criteria: Candidate for potentially curative therapies in the opinion of the investigator. Previous treatment with a PI3K inhibitor or Bruton's tyrosine kinase inhibitor. Prior history of allogeneic hematopoietic stem cell transplant. Prior chemotherapy, cancer immunosuppressive therapy, or other investigational agents within 4 weeks before first dose of study drug. Grade 3B FL and/or clinical evidence of transformation to a more aggressive subtype of lymphoma. Symptomatic central nervous system NHL. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment. Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis C virus antibodies, hepatitis B surface antigen, or hepatitis B core antibodies. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to first dose of study drug.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duvelisib<br> | Drug: Duvelisib<br>* Phosphoinositide-3-kinase (PI3K) inhibitor<br>* Other names: IPI-145;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR, defined as the total percentage of participants who had a best overall response of either complete response (CR) or partial response (PR), was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma. ORR is reported with a 2-sided 95% exact confidence interval. | Every 8-16 weeks while on treatment with duvelisib for up to 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as any adverse event that emerged or worsened in the period from the first dose of study treatment to 30 days after the last dose of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Every 2-8 weeks for up to 73 months | 
| Duration of Response (DOR) | DOR, defined as the time from the first documentation of response to either progressive disease (PD) or death due to any cause, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma. | Every 8-16 weeks for up to 72 months | 
| Progression-free Survival (PFS) | PFS, defined as the time from the first dose of study treatment to the first documentation of either Investigator-assessed PD or death resulting from any cause, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma. | Every 8-16 weeks for up to 72 months | 
| Overall Survival (OS) | OS, defined as the time from the first dose of study treatment to the date of death, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma. | Every 16 weeks for up to 72 months | 
| Plasma Concentration of Duvelisib and IPI-656 | The serum concentration of duvelisib and its main metabolite, IPI-656, are reported for Day 15 of Cycle 1 (C1D15) and Day 1 of Cycle 2 (C2D1) and Day 1 of Cycle 3 (C3D1). Results are reported in nanograms/milliliter (ng/mL). | Every 4 weeks for 12 weeks (C1D15: predose, 1 and 4 hours post dose; C2D1 and C3D1: anytime during study visit) | 
| Time to Response (TTR) | TTR, defined as the time from the first dose of study treatment to the first documentation of response, was evaluated by an independent, third-party panel of radiologists and oncologists (Independent Review Committee [IRC]) according to the revised IWG Response Criteria for Malignant Lymphoma. | First dose to first documentation of complete or partial response (up to 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PI3K Inhibitor