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First generation anti-CD19 chimeric antigen receptor-modified T cells for management of B cell malignances: initial analysis of an ongoing Phase I clinical trial

  • 1,
  • 2,
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Journal for ImmunoTherapy of Cancer20142(Suppl 3):P12

https://doi.org/10.1186/2051-1426-2-S3-P12

Published: 6 November 2014

Keywords

  • Adoptive Transfer
  • Chimeric Antigen Receptor
  • Ongoing Phase
  • Post Infusion
  • Significant Grade

Introduction

Management of advanced B cell malignancies refractory to standard chemotherapy is challenging with sub-optimal results. Recent clinical reports of durable, objective responses from adoptive transfer of anti-CD19 chimeric antigen receptor (CAR) T cells have accentuated the potential of this therapy.

Here we report the preliminary results of an on-going Phase I clinical trial at our Institution.

Methods

This is a single centre, open label, dose escalation, Phase I study of adoptive transfer of autologous T cells expressing a CD19-specific first generation CAR (aCD19z) with pre-conditioning chemotherapy and intravenous interleukin-2 (IL2), in patients with pre-treated CD19-positive malignancy.

We report data on 2 cohorts: Cohort 1 (4 patients) received 1x109 aCD19z T-cells and Cohort 2 (planned 4 patients) 1x1010. Both cohorts received 100,000 u/kg of IL2.

Results

To date, 6 patients have successfully completed treatment. All patients tolerated treatment well, and experienced anticipated transient grade1-2 toxicities attributable to pre-conditioning chemotherapy and IL2. 5 patients developed short lived but significant Grade 4 neutropenia and thrombocytopenia.

4 of 5 patients evaluable to date achieved at least stable disease as best response at 6 weeks post aCD19z T cell infusion, with 1 patient maintaining response at 400+ days. 1 patient achieved a very good partial response with a 65% reduction in disease burden. 2 patients died of disease progression (1 of Central Nervous (CN) progression only, not present at baseline); 2 patients died of viral infection over 400 days post infusion; 1 patient with disease control maintained. No patients died of treatment-related complications.

Quantitative polymerase chain reaction (qPCR) analysis of peripheral blood samples detected aCD19z T cells in both cohorts. Levels peaked at days 4-7 post aCD19z T cell infusion (cohort 1 peak 30% of total cells, cohort 2 (results available to date) peak 25%) before falling to lower levels. All patients revealed persisting low frequency levels (<1%) at week 6; 1 patient at up to 50 weeks. 1 patient received a further course of low dose IL2 at week 6 resulting in a transient increase in zCD19z T cell levels.

All patients demonstrated a significant reduction in peripheral CD19+ T cell numbers post aCD19z T cell infusion, with most substantial results seen in cohort 2 where suppression was seen lasting into week 8 (prior to CN progression).

Discussion

Our data contributes to the encouraging growing body of evidence on antiCD19-specific CAR T cells, suggesting significant clinical responses and sustained persistence. Updated results and immune data will be presented.

Registration Details

Consent

Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Authors’ Affiliations

(1)
Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom
(2)
Cellular Therapeutics Limited, Manchester, United Kingdom
(3)
Clinical Immune and Molecular Monitoring Laboratory, Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, Manchester, United Kingdom
(4)
Clinical and Experimental Immunotherapy Group, Institute of Cancer Sciences, Manchester Academic Healthcare Science Centre, Manchester, United Kingdom

Copyright

© Evans et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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