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

Phase 1

Recruiting

• Conditions: T-cell Acute Lymphoblastic Leukemia; Lymphoblastic T-Cell Lymphoma
• Interventions: Biological: CD1a-CAR T

• Registration Number: NCT05679895
• Lead Sponsor: OneChain Immunotherapeutics

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-22
• Study First Submitted QC: 2023-01-10
• Study First Posted: 2023-01-11
• Study Start: 2023-01-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-02
• Last Update Posted: 2024-04-03
• Primary Completion: 2025-06-25
• Study Completion: 2026-01-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Children older than 2 years or adults, male and female in both groups.

2. Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed.

3. 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:

   1. Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT)
   2. 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.
   3. Refractory first relapse.
   4. Second or further relapse.

4. Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study.

Exclusion Criteria

1. Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), <45%), pulmonary, liver, renal or CNS dysfunction.
2. Allo-HSCT within a timeframe <3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD).
3. Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease.
4. Active bacterial, fungal or viral infection not controlled by adequate treatment.
5. Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection.
6. Women who are pregnant (positive urine/blood pregnancy test) or lactating.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: CD1a-CAR T	CD1a-CAR T	CD1a CAR T cells transduced with a lentiviral vector to express CD1a chimeric receptor domain on T cells administered with a dose-escalation approach.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Remission rate	1 year	Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment.
Minimal residual disease (MRD) response	1 year	Minimal residual disease (MRD) response by flow cytometry: blast count among patients presenting bone marrow complete response (sensitivity 10-4).
Overall survival	1 year	Overall survival time since first OC-1 administration to date of death.
Response rates	1 year	Percentage of patients presenting CR, CRi, Complete remission duration (CRD), morphologic leukaemia-free status (MLFS), and no remission (NR).
Duration of remission	1 year	The duration of the remission will be assessed from the first documented date of remission status until progression (in days)
Persistence of OC-1	1 year	• 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.
Progression-free survival (PFS)	1 year	time since the first OC-1 administration to the documented loss of response.

Trial Locations

Locations (2)

Hospital Clínic; 🇪🇸 Barcelona, Spain

Hospital Sant Joan de Déu; 🇪🇸 Barcelona, Spain