Rituximab Plus Venetoclax in Combination With Zandelisib in Subjects With CLL

Phase 2

Withdrawn

• Conditions: CLL
• Interventions: Drug: Zandelisib; Drug: Rituximab; Drug: Venetoclax

• Registration Number: NCT05209308
• Lead Sponsor: MEI Pharma, Inc.

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-01-12
• Study First Submitted QC: 2022-01-12
• Study First Posted: 2022-01-26
• Study Start: 2022-11-22
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-14
• Primary Completion: 2023-03-15
• Study Completion: 2023-03-15
• Last Update Posted: 2023-03-16

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A	Zandelisib	Ven "low dose" + Rituximab + Zandelisib
Cohort A	Venetoclax	Ven "low dose" + Rituximab + Zandelisib
Cohort A	Rituximab	Ven "low dose" + Rituximab + Zandelisib
Cohort B	Rituximab	Ven "standard dose" + Rituximab + Zandelisib
Cohort B	Venetoclax	Ven "standard dose" + Rituximab + Zandelisib
Cohort B	Zandelisib	Ven "standard dose" + Rituximab + Zandelisib

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	5 years	PFS will be measured as the time from first dose date until progression according the iwCLL criteria or death from any cause.
ORR	2 years	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)

Trial Locations

Locations (4)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Stony Brook University; 🇺🇸 Stony Brook, New York, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Medical Oncology Associates, PS (dba Summit Cancer Centers); 🇺🇸 Spokane, Washington, United States