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

• ClinicalTrials.gov Identifier: NCT03190278
• Recruitment Status: Recruiting
• First Posted: June 16, 2017
• Last Update Posted: February 5, 2024
• Sponsor: Cellectis S.A.
• Information provided by (Responsible Party): Cellectis S.A.

Tracking Information

• First Submitted Date: June 14, 2017
• First Posted Date: June 16, 2017
• Last Update Posted Date: February 5, 2024
• Actual Study Start Date: June 19, 2017
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2024)

• Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability] [ Time Frame: 24 Months ]
  Safety of UCART123v1.2 - Incidence, nature, and severity of AE and SAEs throughout the study
• Dose escalation and expansion part: Occurrence of DLTs [ Time Frame: Up to Day 28 post last UCART123v1.2 infusion ]

Original Primary Outcome Measures (submitted: June 15, 2017)

Incidence, nature, and severity of adverse events and serious adverse events [ Time Frame: Through Day 84 (+/- 7 days), dose limiting toxicities are assessed up to 42 days after UCART123 infusion ]

Adverse events assessed according to common terminology criteria for adverse events (CTCAE v4.03); cytokine release syndrome (CRS); tumor lysis syndrome (TLS); graft vs. host disease (GvHD)

Current Secondary Outcome Measures (submitted: January 31, 2024)

• Investigators assessed overall response rate according to the European Leukemia Net (ELN) Response Criteria [ Time Frame: At Day 28, Day 56, Day 84, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24 ]
• Duration of Response [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From the first day of study treatment to the date of death from any cause, assessed up to Month 24 ]
• Pharmacokinetic (PK) Analysis: Standard PK Analysis will be completed to obtain Maximum plasma concentration (Cmax) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From screening through Day 84 ]
• Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood [ Time Frame: From screening through Day 84 ]
• Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood [ Time Frame: From screening through Day 84 ]
• Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood [ Time Frame: From screening through Day 84 ]
• Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood [ Time Frame: From screening through Day 84 ]

Original Secondary Outcome Measures (submitted: June 15, 2017)

Assessment of Anti-leukemic activity [ Time Frame: Day 14, between Day 28 and Day 35, then every 3 months for one year and every 6 months during the second year after treatment ]

Anti-leukemic activity, as measured by International Working Group (IWG) criteria for AML response criteria

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
• 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
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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

Study Arms

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

Intervention: Biological: UCART123v1.2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 3, 2021): 65
• Original Estimated Enrollment (submitted: June 15, 2017): 156
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Cellectis Central Contact; 1-347-752-4044; clinicaltrials@cellectis.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03190278
• Other Study ID Numbers: UCART123_01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cellectis S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Cellectis S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Gail Roboz, Dr; Weill Medical College of Cornell University

• PRS Account: Cellectis S.A.
• Verification Date: January 2024