Safety and Efficacy of OC-1 Therapy in Patients With R/R T-ALL/LL

Study Overview
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Brief Summary
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First in humans, exploratory, open-label, single-arm, multicentre, non-competitive, dose escalation study to assess the safety and efficacy of CD1a-CAR T therapy in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL)

Official Title
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Safety and Efficacy of hCD1a-CAR T (OC-1) Therapy, in Patients With Relapsed/Refractory (R/R) T-cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LL

Conditions
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T-cell Acute Lymphoblastic Leukemia, Lymphoblastic T-Cell Lymphoma

Intervention / Treatment
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* Biological: CD1a-CAR T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children older than 2 years or adults, male and female in both groups. Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed. R/R CD1a-positive T-ALL/LL patients, including morphologic or MRD-detectable (≥1x10-4) bone marrow and/or extramedullary relapses after 2 therapy lines: Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT) Primary refractoriness, defined as either morphologic persistence or detectable MRD (≥1x10-4) after two standard therapy lines, making the patient not candidate for allo-HSCT. Refractory first relapse. Second or further relapse. Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study. Exclusion Criteria: Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), <45%), pulmonary, liver, renal or CNS dysfunction. Allo-HSCT within a timeframe <3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD). Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease. Active bacterial, fungal or viral infection not controlled by adequate treatment. Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection. Women who are pregnant (positive urine/blood pregnancy test) or lactating.

Ages Eligible for Study
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Minimum Age: 2 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: Experimental: CD1a-CAR T<br>CD1a CAR T cells transduced with a lentiviral vector to express CD1a chimeric receptor domain on T cells administered with a dose-escalation approach. | Biological: CD1a-CAR T<br>* Autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express CD1a chimeric antigen receptor administered by intravenous infusion following a dose-escalation approach<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events grade III-IV | Number of adverse events grade III-IV using common toxicity criteria (CTC) | 1 year particularly the first 28 days after infusion | 
| Incidence of severe Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) | Incidence of severe Cytokine release syndrome (CRS) (≥ grade III) and Immune effector cell-associated neurotoxicity syndrome (ICANS) (≥ grade II) | 1 year particularly the first 28 days after infusion | 
| Non-relapse treatment-related mortality (NRM) | Non-relapse treatment-related mortality (NRM) | 1 year | 
| Number of adverse events of special interest (AESI) | Number of adverse events of special interest (AESI) | 1 year | 
| Assessment of the immunological homeostasis | Assessment of the immunological homeostasis, through the identification of lymphocytes subpopulations by flow cytometry at each study timepoint. | 1 year | 
| Incidence of the treatment-related dermatological events | Incidence of the treatment-related dermatological events | 1 year | 
| Number of patients developing dose limiting toxicity (DLT) | Number of patients developing dose limiting toxicity (DLT) | first 28 days after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate | Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment. | 1 year | 
| Response rates | Percentage of patients presenting CR, CRi, Complete remission duration (CRD), morphologic leukaemia-free status (MLFS), and no remission (NR). | 1 year | 
| Duration of remission | The duration of the remission will be assessed from the first documented date of remission status until progression (in days) | 1 year | 
| Minimal residual disease (MRD) response | Minimal residual disease (MRD) response by flow cytometry: blast count among patients presenting bone marrow complete response (sensitivity 10-4). | 1 year | 
| Progression-free survival (PFS) | time since the first OC-1 administration to the documented loss of response. | 1 year | 
| Overall survival | Overall survival time since first OC-1 administration to date of death. | 1 year | 
| Persistence of OC-1 | • Persistence of OC-1, as determined by flow cytometry and quantitative analysis by qPCR. Genomic copy number integrations of the CAR in peripheral blood (PB) T cells and percentage of CD1a CAR-expressing T cells. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD1a, CAR-T-based therapies