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

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

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)

Study Overview

• Status: Recruiting
• Conditions: T-cell Acute Lymphoblastic Leukemia; Lymphoblastic T-Cell Lymphoma
• Intervention / Treatment: Biological: CD1a-CAR T

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wilmar Castillo; Phone Number: 34 93 403 58 62; Email: wilmar@onechaintx.com
• Study Contact Backup: Name: Laura Astier; Email: laura.astier@bioclever.com

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Clínic
    • Contact: Nuria Martinez
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Joan de Déu
    • Contact: Susana Rives; Phone Number: 34 93 280 40 00

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: 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.	Biological: CD1a-CAR T; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: OneChain Immunotherapeutics
• Collaborators: Hospital Clinic of Barcelona; Hospital Sant Joan de Deu; BioClever 2005 S.L.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): June 25, 2025
• Study Completion (Estimated): January 25, 2026

Study Registration Dates

• First Submitted: December 22, 2022
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T-based therapies; CD1a
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: OC-01-21001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No