Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AMELI-01)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Biological: UCART123v1.2

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cellectis Central Contact; Phone Number: 1-347-752-4044; Email: clinicaltrials@cellectis.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Withdrawn
      • Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60201
      • Recruiting
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Medical College of Cornell University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Abramson Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; UCART123v1.2 tested at several dose levels with different lymphodepletion regimens to establish Maximum Tolerated Dose (MTD) and identify Recommended Phase 2 Dose (RP2D) Dose Expansion: UCART123v1.2 administered at the RP2D determined from the dose escalation phase	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Dose escalation and expansion part: Occurrence of DLTs		Up to Day 28 post last UCART123v1.2 infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
Overall Survival	From the first day of study treatment to the date of death from any cause, assessed up to Month 24
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
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
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
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
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
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
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
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
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
Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood	From screening through Day 84
Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood	From screening through Day 84
Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood	From screening through Day 84
Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood	From screening through Day 84

Collaborators and Investigators

• Sponsor: Cellectis S.A.
• Investigators: Principal Investigator: Gail Roboz, Dr, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Allogeneic; Relapsed/Refractory Acute Myeloid Leukemia; Chimeric Antigen Receptor T-Cell (CAR-T) therapy; Transcription Activator-Like Effector Nuclease (TALEN)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: UCART123_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No