WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study (WT1 TCR-001)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by University College, London
Sponsor:
Collaborators:
Leukaemia Lymphoma Research
Department of Health, United Kingdom
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01621724
First received: March 22, 2012
Last updated: June 15, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukaemia
Chronic Myeloid Leukaemia
Genetic: WT1 TCR-transduced T cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study (WT1 TCR-001)

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Identify organ toxicities and other side effects [ Time Frame: Up to 12 months per patient ] [ Designated as safety issue: Yes ]
  • Transduction efficiency and TCR expression on TCR-transduced cells [ Time Frame: Up to 12 months per patient ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • WT1-specific immune responses of TCR-transduced T cells [ Time Frame: Up to 12 months per patient ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: April 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm cohort study
WT1 TCR-transduced T cells
Genetic: WT1 TCR-transduced T cells

Two patient cohorts:

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

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621724

Contacts
Contact: Emma Morris, Dr 020 7794 0500 ext 33741 e.morris@ucl.ac.uk
Contact: Maria Serrano, Dr 020 7794 0500 ext 34906 maria.serrano@ucl.ac.uk

Locations
United Kingdom
Queen Elizabeth Hospital Not yet recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Charles Craddock, Prof    0121 627 5816    Charles.craddock@uhb.nhs.uk   
Principal Investigator: Charles Craddock, Prof         
University Hospitals Bristol NHS Foundation Trust Not yet recruiting
Bristol, United Kingdom, BS38 3AP
Contact: Stephen Robinson, Dr    0117 342 8523    Stephen.Robinson@ubht.nhs.uk   
Principal Investigator: Stephen Robinson, Dr         
Royal Free Hospital NHS Trust Not yet recruiting
London, United Kingdom, NW3 2QG
Contact: Emma Morris, Dr    020 7794 0500 ext 33741    e.morris@ucl.ac.uk   
Principal Investigator: Emma Morris, Dr         
University College London Hospitals NHS Trust Recruiting
London, United Kingdom, NW1 2PG
Contact: Emma Morris, Dr    0845 155 5000 ext 9712    e.morris@ucl.ac.uk   
Principal Investigator: Emma Morris, Dr         
Royal London Hopspitals NHS Trust Not yet recruiting
London, United Kingdom, EC1M 6BQ
Contact: John Gribben, Prof    020 7882 6052    j.gribben@qmul.ac.uk   
Principal Investigator: John Gribben, Prof         
Sponsors and Collaborators
University College, London
Leukaemia Lymphoma Research
Department of Health, United Kingdom
Investigators
Principal Investigator: Emma Morris, Dr Royal Free and University College London
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01621724     History of Changes
Other Study ID Numbers: UCL 06/154
Study First Received: March 22, 2012
Last Updated: June 15, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
Gene therapy
WT1 TCR
AML
CML

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on September 22, 2014