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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
CD1a-CAR T
Sponsored by
OneChain Immunotherapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-cell Acute Lymphoblastic Leukemia focused on measuring CAR-T-based therapies, CD1a

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital ClínicRecruiting
  • Hospital Sant Joan de DéuRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: CD1a-CAR T

Arm Description

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

Outcomes

Primary Outcome Measures

Number of adverse events grade III-IV
Number of adverse events grade III-IV using common toxicity criteria (CTC)
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)
Non-relapse treatment-related mortality (NRM)
Non-relapse treatment-related mortality (NRM)
Number of adverse events of special interest (AESI)
Number of adverse events of special interest (AESI)
Assessment of the immunological homeostasis
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
Incidence of the treatment-related dermatological events
Number of patients developing dose limiting toxicity (DLT)
Number of patients developing dose limiting toxicity (DLT)

Secondary Outcome Measures

Remission rate
Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment.
Response rates
Percentage of patients presenting CR, CRi, Complete remission duration (CRD), morphologic leukaemia-free status (MLFS), and no remission (NR).
Duration of remission
The duration of the remission will be assessed from the first documented date of remission status until progression (in days)
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).
Progression-free survival (PFS)
time since the first OC-1 administration to the documented loss of response.
Overall survival
Overall survival time since first OC-1 administration to date of death.
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.

Full Information

First Posted
December 22, 2022
Last Updated
February 13, 2023
Sponsor
OneChain Immunotherapeutics
Collaborators
BioClever 2005 S.L., Hospital Clinic of Barcelona, Hospital Sant Joan de Deu
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1. Study Identification

Unique Protocol Identification Number
NCT05679895
Brief Title
Safety and Efficacy of OC-1 Therapy in Patients With R/R T-ALL/LL
Acronym
CARxALL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2023 (Actual)
Primary Completion Date
June 25, 2025 (Anticipated)
Study Completion Date
January 25, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OneChain Immunotherapeutics
Collaborators
BioClever 2005 S.L., Hospital Clinic of Barcelona, Hospital Sant Joan de Deu

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-cell Acute Lymphoblastic Leukemia, Lymphoblastic T-Cell Lymphoma
Keywords
CAR-T-based therapies, CD1a

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: CD1a-CAR T
Arm Type
Experimental
Arm Description
CD1a CAR T cells transduced with a lentiviral vector to express CD1a chimeric receptor domain on T cells administered with a dose-escalation approach.
Intervention Type
Biological
Intervention Name(s)
CD1a-CAR T
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of adverse events grade III-IV
Description
Number of adverse events grade III-IV using common toxicity criteria (CTC)
Time Frame
1 year particularly the first 28 days after infusion
Title
Incidence of severe Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS)
Description
Incidence of severe Cytokine release syndrome (CRS) (≥ grade III) and Immune effector cell-associated neurotoxicity syndrome (ICANS) (≥ grade II)
Time Frame
1 year particularly the first 28 days after infusion
Title
Non-relapse treatment-related mortality (NRM)
Description
Non-relapse treatment-related mortality (NRM)
Time Frame
1 year
Title
Number of adverse events of special interest (AESI)
Description
Number of adverse events of special interest (AESI)
Time Frame
1 year
Title
Assessment of the immunological homeostasis
Description
Assessment of the immunological homeostasis, through the identification of lymphocytes subpopulations by flow cytometry at each study timepoint.
Time Frame
1 year
Title
Incidence of the treatment-related dermatological events
Description
Incidence of the treatment-related dermatological events
Time Frame
1 year
Title
Number of patients developing dose limiting toxicity (DLT)
Description
Number of patients developing dose limiting toxicity (DLT)
Time Frame
first 28 days after infusion
Secondary Outcome Measure Information:
Title
Remission rate
Description
Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment.
Time Frame
1 year
Title
Response rates
Description
Percentage of patients presenting CR, CRi, Complete remission duration (CRD), morphologic leukaemia-free status (MLFS), and no remission (NR).
Time Frame
1 year
Title
Duration of remission
Description
The duration of the remission will be assessed from the first documented date of remission status until progression (in days)
Time Frame
1 year
Title
Minimal residual disease (MRD) response
Description
Minimal residual disease (MRD) response by flow cytometry: blast count among patients presenting bone marrow complete response (sensitivity 10-4).
Time Frame
1 year
Title
Progression-free survival (PFS)
Description
time since the first OC-1 administration to the documented loss of response.
Time Frame
1 year
Title
Overall survival
Description
Overall survival time since first OC-1 administration to date of death.
Time Frame
1 year
Title
Persistence of OC-1
Description
• 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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wilmar Castillo
Phone
34 93 403 58 62
Email
wilmar@onechaintx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Astier
Email
laura.astier@bioclever.com
Facility Information:
Facility Name
Hospital Clínic
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nuria Martinez
Facility Name
Hospital Sant Joan de Déu
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susana Rives
Phone
34 93 280 40 00

12. IPD Sharing Statement

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

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