Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia

Study Overview
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Brief Summary
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The study is in two parts: a dose escalation then a safety dose expansion. The purpose of the dose escalation part is to evaluate the safety and tolerability of ascending doses of UCART19 (dose-escalation part) given as a single infusion in patients with relapsed / refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL), to determine the maximum tolerated dose (MTD), the recommended dose and the lymphodepletion regimen. The purpose of the safety dose expansion is to assess the safety and tolerability of the RD for UCART19.

Official Title
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Phase I, Open Label, Dose-escalation Study Followed by a Safety Expansion Part to Evaluate the Safety, Expansion and Persistence of a Single Dose of UCART19 (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor), Administered Intravenously in Patients With Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukaemia (B-ALL)

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: UCART19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant Age ≥ 16 years Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL) who have exhausted alternative treatment options Estimated life expectancy ≥ 12 weeks (according to investigator's judgement) Eastern Cooperative Oncology Group (ECOG) performance status < 2 Exclusion Criteria: Previous treatment with gene or gene-modified cell therapy medicine products or adoptive T cell therapy Use of previous anti-leukemic therapy (including approved therapies and other investigational products) within 5 half-lives prior to UCART19 administration CD19 negative B-cell leukaemia Burkitt cell or mixed lineage acute leukaemia

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 69 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: UCART19<br> | Biological: UCART19<br> <br> * Other names: S68587;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation part: Dose Limiting Toxicities (DLTs) occurence. Dose expansion part: AE throughout the study. |  | Dose Escalation: Up to day 28 post first UCART19 infusion. Dose Expansion: From inclusion to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability | Adverse events assessed according to NCI-CTCAE v5.0 criteria | From inclusion to Month 12 | 
| Objective Remission Rate | Proportion of patients in whom a response among molecular complete remission (mCR), morphologic complete remission (CR) and complete remission with incomplete blood count recovery (CRi) | At Day 28, Day 84, Month 4, Month 6, Month 9 and Month12 | 
| Duration of remission |  | From the time that response criteria are first met until the date of progression or death (whatever the reason of death), whichever occurs first, assessed up to Month 12 | 
| Time to remission |  | From the date of UCART19 administration until the date that response criteria are met, assessed up to Month 12 | 
| Progression Free Survival (PFS) |  | From the date of UCART19 administration until the date of progression or the date of death (whatever the reason of death), whichever occur first, assessed up to Month 12 | 
| Overall Survival (OS) |  | From the date of UCART19 administration to the date of death from any cause, assessed up to Month 12 |