A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This study will examine the effects of predefined 2-week duvelisib dose holidays on tumor responses and safety/tolerability.

Detailed Description
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This is a Phase 2, randomized, open-label, 2-arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in subjects with R/R iNHL who have received at least 1 prior systemic therapy.

Official Title
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A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma (iNHL)

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: Age ≥ 18 years, ECOG performance status ≤ 2 Histologically confirmed diagnosis of iNHL (Subtypes include FL Grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal), or SLL Must have received 1 prior systemic regimen for iNHL Must have documented radiologic evidence of disease progression, at least 1 bi-dimensionally measurable lesion ≥ 1.5 cm (which has not been previously irradiated), according to 2007 revised IWG criteria, and be a candidate for a subsequent line of therapy. Must have adequate organ function defined by the following laboratory parameters: Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L Platelet count ≥ 75 × 10^9/L Hemoglobin ≥ 8 g/dL Estimated creatinine clearance ≥ 60 mL/min, as determined by the Cockcroft-Gault method Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN) Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) ≤ 3.0 × ULN Exclusion Criteria: Anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of study intervention; palliative radiation therapy is allowed if > 7 days before planned first dose of study interventions, and any toxicity is Grade ≤ 1 Clinical or histological evidence of transformation to a more aggressive subtype of lymphoma or grade 3b FL or Richters' transformation or CLL Prior allogeneic hematopoietic stem cell transplant (HSCT); prior treatment with a PI3K inhibitor History of drug-induced colitis or pneumonitis; TB treatment ≤ 2 years prior to randomization; administration of a live or live attenuated vaccine within 6 weeks of randomization Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention. Baseline QTcF > 500 ms Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects with previous malignancies are eligible if they have been disease-free for 2 years or more. Unstable or severe uncontrolled medical condition that would, in the Investigator's judgment, increase the subject's risk to participating in this study.

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, Continuous and Intermittent Dosing<br>Duvelisib 25 mg BID continuously for 10 weeks, followed by 25 mg BID dosed two weeks on and two weeks off of each subsequent 4-week cycle. | Drug: Duvelisib<br>* PI3K Inhibitor<br>* Other names: Copiktra, VS-0145;|
| Experimental: Duvelisib, Intermittent Dosing<br>Duvelisib 25 mg BID dosed two weeks on and two weeks off. | Drug: Duvelisib<br>* PI3K Inhibitor<br>* Other names: Copiktra, VS-0145;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (Overall Response Rate) | Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria. | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (Progression-free Survival) | From time of first dose of study intervention to PD or death. | 2 years | 
| ORR (Overall Response Rate) | Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria and Lugano Criteria | ORR estimated at 6, 12, 18, and 24 months after first dose of study intervention. | 
| DOR (Duration of Response) | From the time of first response to PD using KM methods. | 2 years | 
| OS (Overall Survival) | From time of first dose of study intervention to death. | 2 years | 
| LNRR (Lymph Node Response Rate) | LNRR will be calculated as the proportion of subjects achieving ≥ 50% decrease in the SPD of target lymph nodes. | 14 months | 
| TTFR (Time To First Relapse) | From the time of first dose of study intervention to time of first CR or PR. | 14 months | 
| Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 | From the time of screening to the end of Safety Follow-Up period of the study. | 14 months | 
| Peak Plasma Concentration (Cmax) |  | 14 months | 
| TTF (Time To Treatment Failure) | From first dose of study intervention until discontinuation for any reason and will be summarized using KM methods. | 2 years | 
| Area under the plasma concentration versus time curve (AUC) |  | 14 months | 

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