Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Relapsed/Refractory Acute Myeloid Leukemia Clinical Trial

— AMELI-01  

Official title:

Phase I, Open Label Dose Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of UCART123 (Allogeneic Engineered T-cells Expressing Anti-CD123 Chimeric Antigen Receptor), Administered in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03190278
• Other study ID #: UCART123_01
• Status: Recruiting
• Phase: Phase 1
• Start date: June 19, 2017
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Cellectis S.A.
• Contact: Cellectis Central Contact
• Phone: 1-347-752-4044
• Email: clinicaltrials[@]cellectis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase I, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of Universal Chimeric Antigen Receptor T-cell (UCART) targeting the Cluster of Differentiation 123 (CD123) in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of Universal Chimeric Antigen Receptor T-cells targeting CD123 (UCART123v1.2) and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Main Inclusion Criteria:

• Patients with relapsed or primary refractory AML (as defined in World Health Organization [WHO] criteria) with =5% bone marrow blasts
• Patients with CD123+ blast cells (verified by flow cytometry)
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of =1
• Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within screening period
• (Dose-escalation) Identified donor and transplant strategy prior to lymphodepletion (LD)
• Other criteria may apply

Main Exclusion Criteria:

• Patients with acute promyelocytic leukemia (APL) or central nervous system (CNS) Leukemia
• Previous investigation gene or cell therapy (including CAR)
• > 1 prior allogeneic stem cell transplantations (SCTs)
• Prior treatment with rituximab or other anti-cluster of differentiation 20 (anti-CD20) therapy within 3 months
• Any known active or uncontrolled infection
• Other criteria may apply

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Relapsed/Refractory Acute Myeloid Leukemia

Intervention

Biological:
• UCART123v1.2
Allogeneic engineered T-cells expressing anti-CD123 Chimeric Antigen Receptor Biological/vaccine: CLLS52 A monoclonal antibody that recognizes the CD52 antigen Other Names: Alemtuzumab

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Weill Medical College of Cornell University	New York	New York
United States	University of Pennsylvania - Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cellectis S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability]	Safety of UCART123v1.2 - Incidence, nature, and severity of AE and SAEs throughout the study	24 Months
Primary	Dose escalation and expansion part: Occurrence of DLTs		Up to Day 28 post last UCART123v1.2 infusion
Secondary	Investigators assessed overall response rate according to the European Leukemia Net (ELN) Response Criteria		At Day 28, Day 56, Day 84, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24
Secondary	Duration of Response		From the date of the initial response to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24
Secondary	Progression Free Survival		From the first day of study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24
Secondary	Overall Survival		From the first day of study treatment to the date of death from any cause, assessed up to Month 24
Secondary	Pharmacokinetic (PK) Analysis: Standard PK Analysis will be completed to obtain Maximum plasma concentration (Cmax)		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain time to reach Cmax (Tmax)		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain total area under curve from zero to infinity (AUC-infinity)		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Rate		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Half-life		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Clearance		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Volume of Distribution		alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
Secondary	Pharmacodynamic Analysis: Pharmacodynamics Monitoring of the incidence of anti-cluster of differentiation 52 (anti-CD52; alemtuzumab) antibodies (ADA) in serum Pre-alemtuzumab administration and through Day 84		From screening through Day 84
Secondary	Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood		From screening through Day 84
Secondary	Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood		From screening through Day 84
Secondary	Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood		From screening through Day 84
Secondary	Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood		From screening through Day 84