Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Phase I, first-in-human, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of UCART targeting CD123 in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of UCART123v1.2 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).

Official Title
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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

Conditions
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Relapsed/Refractory Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: UCART123v1.2


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Patients with relapsed or primary refractory AML (as defined in 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 APL or CNS Leukemia Previous investigation gene or cell therapy (including CAR) ≥ 2 prior allogeneic SCTs Prior treatment with rituximab or other anti-CD20 therapy within 3 months Any known active or uncontrolled infection Other criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Several tested doses of UCART123v1.2 with different lymphodepletion regimens to establish Maximum Tolerated Dose (MTD) and identify Recommended Phase 2 Dose (RP2D) Dose Expansion: UCART123v1.2 administered at the selected dose determined from the dose escalation phase | Biological: UCART123v1.2<br>* Allogeneic engineered T-cells expressing anti-CD123 Chimeric Antigen Receptor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AE/SAE/DLT [Safety and Tolerability] | Safety of UCART123v1.2 - Incidence, nature, and severity of adverse events and serious adverse events (SAEs) throughout the study | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Assessment |  | 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 |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, Chimeric Antigen Receptor T-Cell (CAR-T) therapy, Allogeneic, Transcription Activator-Like Effector Nuclease (TALEN)