CD19-CAR Immunotherapy for Childhood Acute Lymphoblastic Leukemia (ALL)

Phase 1

Terminated

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Genetic: donor-derived EBV-specific cytotoxic T-cells (EBV-CTL) transduced with the retroviral vector SFGalpha-CD19-CD3zeta; Biological: Irradiated donor-derived Lymphoblastoid Cell Line

• Registration Number: NCT01195480
• Lead Sponsor: University College, London

Brief Summary

The aim of this clinical trial is to evaluate the feasibility, safety and biological effect of adoptive transfer of CD19ζ chimaeric receptor transduced donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTL) in patients with high-risk or relapsed B cell precursor ALL after allogeneic Haematopoietic Stem Cell Transplantation (HSCT).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-09-03
• Study First Submitted QC: 2010-09-03
• Study First Posted: 2010-09-06
• Study Start: 2012-05
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-16
• Last Update Posted: 2018-05-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylaxis arm	Irradiated donor-derived Lymphoblastoid Cell Line	Patients who have relapsed in the bone marrow after previous myeloablative HSCT and achieve remission after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells after a second HSCT with reduced intensity conditioning.
Pre-emptive arm	donor-derived EBV-specific cytotoxic T-cells (EBV-CTL) transduced with the retroviral vector SFGalpha-CD19-CD3zeta	In this arm, patients identified at high (\> 50%) risk of relapse will be eligible for generation of donor-derived EBV CTL immediately prior to HSCT. These patients will be monitored for evidence of MRD in regular bone marrow aspirates for the first year post-HSCT. MRD positivity post-HSCT is highly predictive of subsequent relapse. In those patients who become MRD+ in the marrow at a level of minimum 5 x 10-4, cryopreserved CTL that have been transduced with a retroviral vector carrying the CD19-zeta transgene will be thawed and administered to the patient pre-emptively.
Prophylaxis arm	donor-derived EBV-specific cytotoxic T-cells (EBV-CTL) transduced with the retroviral vector SFGalpha-CD19-CD3zeta	Patients who have relapsed in the bone marrow after previous myeloablative HSCT and achieve remission after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells after a second HSCT with reduced intensity conditioning.
Pre-emptive arm	Irradiated donor-derived Lymphoblastoid Cell Line	In this arm, patients identified at high (\> 50%) risk of relapse will be eligible for generation of donor-derived EBV CTL immediately prior to HSCT. These patients will be monitored for evidence of MRD in regular bone marrow aspirates for the first year post-HSCT. MRD positivity post-HSCT is highly predictive of subsequent relapse. In those patients who become MRD+ in the marrow at a level of minimum 5 x 10-4, cryopreserved CTL that have been transduced with a retroviral vector carrying the CD19-zeta transgene will be thawed and administered to the patient pre-emptively.

Primary Outcome Measures

Name	Time	Method
Toxicity attributable to transfer of CD19-zeta transduced CTL	1 year	1. Incidence of grade 3-5 toxicity attributable to transfer of CD19-zeta transduced CTL within 12 weeks of infusion.; 2. Incidence of significant (Grade II-IV) and severe (Grade III-IV) acute GVHD before day 100 and limited/extensive chronic GVHD between day 100-365.; 3. Incidence of hypogammaglobulinaemia after CD19-zeta CTL transfer at day 100, 6 months and 1 year post-HSCT
Biological efficacy as assessed by effect of CD19-zeta transduced CTL on Minimal Residual Disease levels in the bone marrow in the first year post- transduced CTL infusion	1 year

Secondary Outcome Measures

Name	Time	Method
Persistence and frequency of circulating CD19-zeta transduced CTL in the peripheral blood of recipients after adoptive transfer as assessed by flow cytometry and quantitative real-time PCR.	1 year
Relapse rate, disease-free survival and overall survival at 1 and 2 years after adoptive immunotherapy with CD19ζ-transduced EBV-CTL	2 years
In vitro anti-leukaemic response of circulating PBMC post adoptive transfer of CD19-zeta transduced CTL using interferon-gamma ELISPOT assays after stimulation with CD19+ve targets	1 year

Trial Locations

Locations (7)

Medizinische Hochschule; 🇩🇪 Hannover, Germany

University College London Hospital; 🇬🇧 London, United Kingdom

Hospital for Children and Adolescents III, Goethe University; 🇩🇪 Frankfurt, Germany

University Children's Hospital; 🇩🇪 Münster, Germany

Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum; 🇩🇪 Essen, Germany

Bristol Children's Hospital; 🇬🇧 Bristol, United Kingdom

Great Ormond Street Hospital for Children; 🇬🇧 London, United Kingdom