Back to resultsWT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
Primary Purpose
Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
WT1 TCR-transduced T cells
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukaemia focused on measuring Gene therapy, WT1 TCR, AML, CML
Eligibility 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.
Sites / Locations
- University Hospitals Bristol NHS Foundation Trust
- University College London Hospitals NHS Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm cohort study
Arm Description
WT1 TCR-transduced T cells
Outcomes
Primary Outcome Measures
Identify organ toxicities and other side effects
Transduction efficiency and TCR expression on TCR-transduced cells
Secondary Outcome Measures
WT1-specific immune responses of TCR-transduced T cells
Full Information
NCT ID
NCT01621724
First Posted
March 22, 2012
Last Updated
October 1, 2018
Sponsor
Cell Medica Ltd
Collaborators
University College, London, Cell Therapy Catapult
1. Study Identification
Unique Protocol Identification Number
NCT01621724
Brief Title
WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
Official Title
WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
May 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cell Medica Ltd
Collaborators
University College, London, Cell Therapy Catapult
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia
Keywords
Gene therapy, WT1 TCR, AML, CML
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm cohort study
Arm Type
Experimental
Arm Description
WT1 TCR-transduced T cells
Intervention Type
Genetic
Intervention Name(s)
WT1 TCR-transduced T cells
Intervention Description
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
Primary Outcome Measure Information:
Title
Identify organ toxicities and other side effects
Time Frame
Up to 12 months per patient
Title
Transduction efficiency and TCR expression on TCR-transduced cells
Time Frame
Up to 12 months per patient
Secondary Outcome Measure Information:
Title
WT1-specific immune responses of TCR-transduced T cells
Time Frame
Up to 12 months per patient
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emma Morris, Dr
Organizational Affiliation
University College, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Bristol NHS Foundation Trust
City
Bristol
ZIP/Postal Code
BS38 3AP
Country
United Kingdom
Facility Name
University College London Hospitals NHS Trust
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
We'll reach out to this number within 24 hrs