WT1 TCR gene therapy for leukaemia: a phase I/II safety and toxicity study (WT1 TCR-001)

Not Applicable

Completed

• Conditions: Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic), Leukaemia (acute myeloid); Cancer; Leukaemia (chronic)

• Registration Number: ISRCTN11622375
• Lead Sponsor: niversity College London (UCL) (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-03-31
• Study Completion: 2012-01-17
• Last Update Posted: 4 May 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

General inclusion criteria:
All patients will undergo detailed laboratory based assessment prior to the procedure:
1. Aged greater than or equal to 18 years and less than or equal to 75 years
2. Life expectancy greater than 1626 weeks (46 months)
3. World Health Organisation (WHO) performance status of 0 - 2
4. HLA A*0201 positive
5. Completed previous course of chemotherapy greater than or equal to 4 weeks prior to commencing the initial phase of the trial (leucapheresis for collection of patient peripheral blood mononuclear cells [PBMC])
7. Peripheral blood total lymphocyte count greater than 0.5 x 10^9/L
8. Informed consent in writing and ability to co-operate with treatment and follow up
9. Willing, able and available for collection of PBMC/T-cells by leucapheresis
10. Hepatitis B and C, HTLV-1, human immunodeficiency virus (HIV) negative
11. Free from serious concurrent illness
12. 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
13. Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards
14. Haematological and Biochemical Indices:
14.1. Haemoglobin (Hb) = 7.0 g/dl; neutrophils = 0.2 x 10^9/L; total lymphocytes >0.5 x 10^9/L; platelets (Plts) = 40 x 10^9/L
14.2. Serum bilirubin, Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) less than 3 x upper normal limit
14.3. Calculated creatinine clearance = 30 ml/min (uncorrected value) or isotope clearance measurement = 30 ml/min

Disease-specific inclusion criteria:
AML or CML proven by morphology, histology, immunophenotyping and cytogenetics (where available):

1. Acute myeloid leukaemia (AML):
Patients not eligible for BMT procedure with:
1.1. AML in 2nd CR or greater
1.2. Good and Standard Risk* AML in 1st CR or PR in patients greater than 60 years; and
1.3. Poor Risk* AML in 1st CR CR/PR or later (slow remitters and/or adverse cytogenetics)
1.4. AML at 1st relapse post BMT in CR or PR after re-induction and consolidation.
[NB, *risk category as defined by MRC criteria: Good Risk: t(15;17), t(8;21), inv 16; Poor Risk: -5; -7; del (5q); abn (3q) or complex (=/>4 abn)].

2. Chronic myeloid leukaemia (CML):
2.1. Patients in chronic phase resistant to Glivec/Imatinib and 2nd generation tyrosine kinase inhibitors (e.g., Dasatinib), AND NOT eligible for allogeneic BMT
2.2. Patients in chronic phase resistant to Glivec/Imatinib and with an identified mutation known to be resistant to 2nd generation tyrosine kinase inhibitors, AND NOT eligible for allogeneic BMT
2.3. Patients = 50 years (and ineligible for myeloablative allo-BMT), with a suboptimal response to Glivec/Imatinib and an identified mutation known to be resistant to 2nd generation tyrosine kinase inhibitors. These patients are at high risk of disease progression. Patients in this group would stop Glivec/Imatinib prior to leu

Exclusion Criteria

1. Aged less than 18 years or greater than 75 years
2. Patients should not receive concurrent systemic corticosteroids whilst on the study
3. Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered
4. Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection
5. Patients with any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial
6. Patients known to be serologically positive for Hepatitis B, C, HTLV-1 or HIV
7. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease
8. Positive pregnancy test or reluctance to use contraception
9. Pregnant and lactating women are excluded
10. History of severe allergy

Study & Design

• Study Type: Interventional
• Study Design: Not specified