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

NCT01621724 | Completed Phase 1 DMC

• 1 other identifier: D-00272-CT2014001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Myeloid Leukaemia; Chronic Myeloid Leukaemia

Keywords

Gene therapy; WT1 TCR; AML; CML

Outcome Measures

Primary Outcomes (2)

• Identify organ toxicities and other side effects

  Up to 12 months per patient

• Transduction efficiency and TCR expression on TCR-transduced cells

  Up to 12 months per patient

Secondary Outcomes (1)

• WT1-specific immune responses of TCR-transduced T cells

  Up to 12 months per patient

Study Arms (1)

Single arm cohort study

EXPERIMENTAL

WT1 TCR-transduced T cells

Genetic: WT1 TCR-transduced T cells

Interventions

WT1 TCR-transduced T cells GENETIC

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

Single arm cohort study

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cell Medica Ltd: lead
• University College, London: collaborator
• Cell Therapy Catapult: collaborator

Study Sites (2)

University Hospitals Bristol NHS Foundation Trust

Bristol, BS38 3AP, United Kingdom

Location

University College London Hospitals NHS Trust

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emma Morris, Dr

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2012
• First Posted: June 18, 2012
• Study Start: April 1, 2012
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: October 2, 2018

Record last verified: 2018-10

Locations

GB (2)