Dose-escalation, Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Patients with R/r NHL and R/r B-cell ALL

Phase 1

Recruiting

• Conditions: B-cell Acute Lymphoblastic Leukemia; Non-Hodgkin Lymphoma
• Interventions: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: IL-2; Drug: Bendamustine

• Registration Number: NCT03666000
• Lead Sponsor: Imugene Limited

Brief Summary

This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL and r/r B-cell NHL.

Detailed Description

This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find an appropriate dose to optimize safety and efficacy, and evaluate clinical activity of azer-cel in participants with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL). Before initiating azer-cel, participants will be administered lymphodepletion (LD). At Day 0 of the Treatment Period, participants will receive an intravenous (IV) infusion of azer-cel. All participants will be monitored through D720 or progression. All participants who receive a dose of azer-cel will be followed in a separate long-term follow-up (LTFU) study for up to 15 years after exiting this study.

Study Timeline

• Study First Submitted: 2018-08-20
• Study First Submitted QC: 2018-09-07
• Study First Posted: 2018-09-11
• Study Start: 2019-03-11
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-16
• Primary Completion: 2025-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 129

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Level 4b	IL-2	Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Dose Level 3a	Cyclophosphamide	Azer-cel, 3 x 10\^6 CAR T cells per kg body weight.
Dose Level 4b	Azer-cel	Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Dose Level 2	Fludarabine	Azer-cel, 1 x 10\^6 CAR T cells per kg body weight
Dose Level 3a	Azer-cel	Azer-cel, 3 x 10\^6 CAR T cells per kg body weight.
Dose Level 3a	Fludarabine	Azer-cel, 3 x 10\^6 CAR T cells per kg body weight.
Dose Level 1	Azer-cel	Azer-cel 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion.
Dose Level 1	Cyclophosphamide	Azer-cel 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion.
Dose Level 2	Azer-cel	Azer-cel, 1 x 10\^6 CAR T cells per kg body weight
Dose level 4c	Azer-cel	Azer-cel, 1000 x 10\^6 CAR T cells (flat dose) given as 2 administrations of 500 × 106 cells/per dose on Day 0 and Day 5.
Dose level 4c	Fludarabine	Azer-cel, 1000 x 10\^6 CAR T cells (flat dose) given as 2 administrations of 500 × 106 cells/per dose on Day 0 and Day 5.
Dose Level 4	Azer-cel	Azer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight administered after a single lymphodepletion.
Dose Level 4	Fludarabine	Azer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight administered after a single lymphodepletion.
Dose Level 4b	Cyclophosphamide	Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Dose Level 1	Fludarabine	Azer-cel 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion.
Dose Level 2	Cyclophosphamide	Azer-cel, 1 x 10\^6 CAR T cells per kg body weight
Dose Level 4	Cyclophosphamide	Azer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight administered after a single lymphodepletion.
Dose Level 4b	Fludarabine	Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Dose Level 4b	Bendamustine	Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Dose level 4c	Cyclophosphamide	Azer-cel, 1000 x 10\^6 CAR T cells (flat dose) given as 2 administrations of 500 × 106 cells/per dose on Day 0 and Day 5.

Primary Outcome Measures

Name	Time	Method
Phase 1b Dose Expansion: Objective response rate (ORR): Dose expansion only	Up to day 720	- NHL: Lugano criteria
Phase 1 Dose Escalation/Phase 1b Dose Expansion: Frequency of Participants with Azer-cel related Adverse Events (AEs) defined as dose limiting toxicities (DLTs)	Up to day 720

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	Up to day 720	- Defined as the duration (days) from initial response to disease progression or death.
Number of Participants with AEs	Up to day 720	- Defined as all AEs of clinical significance captured on study and specific reporting of DLTs, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interests (AESIs), and AEs related to study treatment.
Objective Response Rate (ORR): Dose escalation only	Up to day 720	* B-ALL: National Comprehensive Cancer Network (NCCN) 2017 criteria; * NHL: Lugano criteria
Progression-free survival (PFS)	Up to day 720	- Defined as the duration (days) from Day 0 to disease progression or death.
Time to next treatment (TNT)	Up to day 720	- Defined as the duration (days) from Day 0 to institution of next systemic therapy.
Complete response (CR) rate	Up to day 720	* B-ALL: National Comprehensive Cancer Network (NCCN) 2017 criteria; * NHL: Lugano criteria
Overall survival (OS)	Up to day 720	- Defined as the duration (days) from Day 0 to death.

Trial Locations

Locations (21)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

City of Hope; 🇺🇸 Duarte, California, United States

H. Lee Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Winship Cancer Institute Emory University; 🇺🇸 Atlanta, Georgia, United States

Northside Hospital Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

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

Barbara Ann Karmanos Cancer Institute (Wayne State University); 🇺🇸 Detroit, Michigan, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Weill Cornell Medical College - NY Presbyterian Hospital; 🇺🇸 New York, New York, United States

Columbia University Irving Medical Center/New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Lifespan Cancer Institute at Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia