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WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01621724
Recruitment Status : Completed
First Posted : June 18, 2012
Last Update Posted : October 2, 2018
University College, London
Cell Therapy Catapult
Information provided by (Responsible Party):
Cell Medica Ltd

Tracking Information
First Submitted Date  ICMJE March 22, 2012
First Posted Date  ICMJE June 18, 2012
Last Update Posted Date October 2, 2018
Study Start Date  ICMJE April 2012
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2012)
  • Identify organ toxicities and other side effects [ Time Frame: Up to 12 months per patient ]
  • Transduction efficiency and TCR expression on TCR-transduced cells [ Time Frame: Up to 12 months per patient ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2012)
WT1-specific immune responses of TCR-transduced T cells [ Time Frame: Up to 12 months per patient ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
Official Title  ICMJE WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
Brief Summary

WT1 TCR gene therapy is a new treatment for acute myeloid leukaemia and chronic myeloid leukaemia.

Patient's white blood cells (T cells) are modified to specifically fight the leukaemia cells by transferring a gene into the T cells, which allows them to recognize fragments of a protein called WT1. This protein is present on the surface of leukaemia cells at very high levels. The gene transferred to the T cells enables them to make a new T cell receptor (TCR), which will allow them to attack leukaemia cells with high levels of WT1 on their surface.

Using this form of gene therapy the investigators can convert some of the patient's immune system's own T cells into T cells that the investigators hope will be much more effective at recognizing and killing leukaemia cells.

Detailed Description

This trial concerns a novel approach to generating leukaemia antigen-specific T cells for adoptive cellular therapy in HLA-A*0201 patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML)

In this study, patient T cells will be gene-modified using a GMP grade retroviral vector containing the genes for a WT1-specific, HLA-A2-restricted T cell receptor. This ex vivo gene therapy will generate T cells expressing the WT1-specific TCR and thus able to recognise WT1-expressing target cells.

The autologous Cys1 WT1 TCR-transduced T cells will be re-infused back into adult leukaemia patients following lymphodepleting conditioning.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukaemia
  • Chronic Myeloid Leukaemia
Intervention  ICMJE Genetic: WT1 TCR-transduced T cells

Two patient cohorts:

Cohort 1 (up to 6 patients) = ≤ 2 x 107/kg WT1 TCR-transduced T cells

Cohort 2 (12 patients)= ≤ 108/kg WT1 TCR-transduced T cells

Study Arms  ICMJE Experimental: Single arm cohort study
WT1 TCR-transduced T cells
Intervention: Genetic: WT1 TCR-transduced T cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: June 15, 2012)
Actual Study Completion Date  ICMJE May 2018
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

General Inclusion Criteria:

  • Age ≥ 18 years and ≤ 75 years.
  • Life expectancy ≥ 16 weeks (4 months).
  • World Health Organisation (WHO) performance status of 0-2
  • HLA A*0201 positive
  • Completed previous course of chemotherapy ≥ 4 weeks prior to commencing the initial phase of the trial (leucapheresis for collection of patient PBMC).
  • Peripheral blood total lymphocyte count > 0.5x109/L.
  • Informed consent in writing and ability to co-operate with treatment and follow up.
  • Willing, able and available for collection of PBMC/ T cells by leucapheresis.
  • Hepatitis B and C, HTLV-1, Syphilis, HIV negative.
  • Free from serious concurrent illness.
  • Female patients of child-bearing age must have a negative pregnancy test and agree to use reliable contraceptive methods for the duration of the therapy and for 6 months afterwards.
  • Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards.
  • Haematological and Biochemical Indices:
  • Haemoglobin (Hb) ≥ 7.0 g/dl; neutrophils ≥ 0.2 x 109/L; total lymphocytes > 0.5 x 109/L; platelets (Plts) ≥ 40 x 109/L
  • serum bilirubin, Alanine amino-transferase (ALT) and/or aspartate amino transferase (AST) < 3 x upper normal limit
  • calculated creatinine clearance ≥ 30 ml/min (uncorrected value) or isotope clearance measurement ≥ 30ml/min

Further disease specific inclusion criteria are detailed in Protocol

Exclusion Criteria:

  • Age < 18 years or > 75 years.
  • Patients should not receive concurrent systemic corticosteroids whilst on the study.
  • Within three months of having received fludarabine (at time of leucapheresis).
  • Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered.
  • Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection.
  • Patients with any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
  • Patients known to be serologically positive for Hepatitis B, C, HTLV-1 Syphilis or HIV.
  • Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease
  • Positive pregnancy test or reluctance to use contraception.
  • Pregnant and lactating women are excluded.
  • History of Severe Allergy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01621724
Other Study ID Numbers  ICMJE D-00272-CT2014001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cell Medica Ltd
Study Sponsor  ICMJE Cell Medica Ltd
Collaborators  ICMJE
  • University College, London
  • Cell Therapy Catapult
Investigators  ICMJE
Principal Investigator: Emma Morris, Dr University College, London
PRS Account Cell Medica Ltd
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP