CARxALL: Safety and Efficacy of OC-1 Therapy in Patients With R/R T-ALL/LL
Study Details
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)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
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Outcome Measures
Primary Outcome Measures
- 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)
- 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)
- Non-relapse treatment-related mortality (NRM) [1 year]
Non-relapse treatment-related mortality (NRM)
- 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
- Number of patients developing dose limiting toxicity (DLT) [first 28 days after infusion]
Number of patients developing dose limiting toxicity (DLT)
Secondary Outcome Measures
- Remission rate [1 year]
Percentage of patients presenting complete response (CR) or incomplete count recovery (CRi) at any point after treatment.
- 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)
- 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).
- Progression-free survival (PFS) [1 year]
time since the first OC-1 administration to the documented loss of response.
- Overall survival [1 year]
Overall survival time since first OC-1 administration to date of death.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Children older than 2 years or adults, male and female in both groups.
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Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed.
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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:
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Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT)
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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.
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Refractory first relapse.
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Second or further relapse.
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Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study.
Exclusion Criteria:
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Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), <45%), pulmonary, liver, renal or CNS dysfunction.
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Allo-HSCT within a timeframe <3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD).
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Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease.
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Active bacterial, fungal or viral infection not controlled by adequate treatment.
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Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection.
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Women who are pregnant (positive urine/blood pregnancy test) or lactating.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hospital Clínic | Barcelona | Spain | ||
2 | Hospital Sant Joan de Déu | Barcelona | Spain |
Sponsors and Collaborators
- OneChain Immunotherapeutics
- BioClever 2005 S.L.
- Hospital Clinic of Barcelona
- Hospital Sant Joan de Deu
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OC-01-21001