Rituximab Plus Venetoclax in Combination With Zandelisib in Subjects With CLL

Study Overview
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Brief Summary
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A Phase 2 study of Zandelisib with Venetoclax (VEN) and Rituximab (R) in subjects with Relapsed/Refractory CLL.

Detailed Description
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This is an open label Phase 2 clinical study of Zandelisib with Venetoclax (VEN) and Rituximab (R) in subjects with R/R CLL. VEN and R will be administered per standard of care. Subjects must have histologically confirmed relapsed/refractory CLL and received ≥1 lines of prior therapy A total 42 subjects will be enrolled and treated with zandelisib in combination with VEN + R.

Official Title
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A Phase 2 Single-Arm, Open-Label Study to Assess the Safety and Efficacy of Rituximab Plus Venetoclax in Combination With Zandelisib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia - The CORAL Study

Conditions
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CLL

Intervention / Treatment
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* Drug: Zandelisib
* Drug: Rituximab
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥18 years Histologically confirmed relapsed/refractory CLL who received ≥1 lines of prior therapy At least one bi-dimensionally measurable nodal lesion >1.5 cm Adequate renal, hepatic function Adequate hematologic parameters at screening Exclusion Criteria: Subjects who relapsed or progressed on BCL-2 inhibitor Relapsed within 2 years of discontinuation of prior PI3K inhibitor (PI3Ki) therapy or disease progression on PI3Ki therapy History or currently active HBV, HCV; any uncontrolled active infection, HIV infection; HIV-related lymphoma History of Richter's transformation or prolymphocytic leukemia Known allergies to both xanthine oxidase inhibitors and rasburicase, or any excipients of the drug products Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure Pregnant women

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This open label study is composed of 2 cohorts: A safety run-in Cohort A followed by Cohort B. Both cohorts will follow the same dosing schedule and subjects will receive Zandelisib, however in Cohort A, VEN will be administered at a different dose then Cohort B.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Ven low dose + Rituximab + Zandelisib | Drug: Zandelisib<br>* Zandelisib taken orally for 7 days of each 28 day cycle<br>* Other names: ME-401;Drug: Rituximab<br>* Rituximab IV for 6 cycles<br>* Other names: MabThera;Drug: Venetoclax<br>* Orally - Ramp up weeks 1-5<br>* Other names: Venclexta;|
| Experimental: Cohort B<br>Ven standard dose + Rituximab + Zandelisib | Drug: Zandelisib<br>* Zandelisib taken orally for 7 days of each 28 day cycle<br>* Other names: ME-401;Drug: Rituximab<br>* Rituximab IV for 6 cycles<br>* Other names: MabThera;Drug: Venetoclax<br>* Orally - Ramp up weeks 1-5<br>* Other names: Venclexta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the uMRD rate in PB and BM by flow cytometry | measured by 8-color flow cytometry with a quantitative lower limit of detection of at least 10-4 (1 in 10,000 cells). | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The ORR will be measured by the proportion of subjects having achieved a CR/CRi (CR with incomplete recovery in BM) or partial response (PR) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2018) | 2 years | 
| Progression Free Survival | PFS will be measured as the time from first dose date until progression according the iwCLL criteria or death from any cause. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia