Phase 1/2 Study of UCART22 in Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia (BALLI-01)

Study Overview
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Brief Summary
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This is a first-in-human, open-label, dose escalation and expansion study of UCART22 administered intravenously to patients with relapsed or refractory B-cell acute Lymphoblastic Leukemia (B-ALL). The purpose of this study is to evaluate the safety and clinical activity of UCART22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Official Title
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Open Label Dose-escalation and Dose-expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART22 (Allogeneic Engineered T-cells Expressing Anti-CD22 Chimeric Antigen Receptor) in Patients With Relapsed or refractoryCD22+ B-cell Acute Lymphoblastic Leukemia (B-ALL)

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: UCART22
* Biological: CLLS52


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B-ALL blast cells expressing CD22 Diagnosed with R/R B-ALL Prior therapy must include at least one standard chemotherapy regimen and at least one salvage regimen Exclusion Criteria: -Prior cellular therapy or investigational cellular or gene therapy within 60 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 70 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: Dose Escalation<br>Several tested doses of UCART22 until the Maximum Tolerated Dose (MTD) is identified and establish Recommended Phase 2 Dose (RP2D) Dose Expansion: UCART22 administered at the RP2D | Biological: UCART22<br>* Allogeneic engineered T-cells expressing anti-CD22 Chimeric Antigen Receptor given following a lymphodepleting regimen<br>Biological: CLLS52<br>* A monoclonal antibody that recognizes a CD52 antigen<br>* Other names: Alemtuzumab;|

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] | Incidence, nature, and severity of adverse events and serious adverse events (SAEs) throughout the study in relation to UCART22 and/or lymphodepletion | 24 Months | 
| Dose escalation part: Occurrence of Dose Limiting Toxicities (DLTs) |  | Up to D28 post initial UCART22 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator assessed overall response rate according to the Response criteria for Acute Lymphoblastic Leukemia (ALL) |  | 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 | 
| Pharmacokinetic (PK) profile/exposure levels of CLLS52 (Alemtuzumab) used during lymphodepletion |  | Lymphodepletion to Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell Acute Lymphoblastic Leukemia (B-ALL), Relapse/Refractory B-ALL, Universal Chimeric Antigen Receptor T-Cell (UCAR-T) Therapy, Allogeneic, Transcription Activator-Like Effector Nuclease (TALEN®)