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Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia Using CAR T-cells to Target CD19

2016-10-18 02:08:21 | BioPortfolio

Summary

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16 to 65 years) with high risk, relapsed/refractory CD19+ B-ALL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with a lentiviral vector to generate the CD19CAT-41BBZ CAR T-cells (referred to subsequently as CD19CAR T-cells). Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. Patients will receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3).

The study is designed as an intra-patient dose escalation employing a total dose range (over 2 doses, Dose 1 and Dose 2) of between 5 x 106 CD19CAR T-cells and 1.1 x 109 CD19CAR T-cells. The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL.

After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 5 years post-CD19CAR T-cell infusion.

Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16 to 65 years) with high risk, relapsed/refractory CD19+ B-ALL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with a lentiviral vector to generate the CD19CAT-41BBZ CAR T-cells (referred to subsequently as CD19CAR T-cells). Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. Patients will receive pre-conditioning lymphodepleting (LD) chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3).

The study is designed as an intra-patient dose escalation employing a total dose range (over 2 doses, Dose 1 and Dose 2) of between (minimum) 5 x 106 CD19CAR T-cells (plus 20% for thawing losses) and (maximum) 1.1 x 109 CD19CAR T-cells (plus 20% for thawing losses).

The initial ATIMP dose administered is dependent upon B-ALL disease burden in the bone marrow. For patients with <20% marrow infiltration by B-ALL at baseline (screening), Dose 1a will be 1x108 CD19CAR T-cells and will be administered on Day 0 following LD. For those with ≥20% marrow infiltration by B-ALL, Dose 1b, administered on Day 0, will be 1x107 CD19CAR T-cells. This measure to prevent toxicity is in keeping with published data correlating severity of CRS with disease burden.

Dose 1a* (BM blasts≤20%): 1x108 CD19CAR T-cells (plus 20% for thawing losses) Dose 1b* (BM blasts>20%): 1x107 CD19CAR T-cells (plus 20% for thawing losses) Dose 2* (all patients, in the absence of clinically severe CRS): dosing range between minimum dose of ≥5 x 106 CD19CAR T-cells (plus 20% for thawing losses) and maximum dose of ≤1x109 CD19CAR T-cells (plus 20% for thawing losses)

*Minimum dose permitted on trial at all Dose levels is ≥5 x 106 CD19CAR T-cells (plus 20% for thawing losses) The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL. After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 5 years post-CD19CAR T-cell infusion.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Leukemia, Lymphoblastic, Acute

Intervention

CD19CAT-41BBZ CAR T-cells

Status

Not yet recruiting

Source

University College, London

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-10-18T02:08:21-0400

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