Acute Myeloid Leukaemia and Chronic Myeloid Leukaemia in adults. MedDRA version: 20.0 Level: PT Classification code 10009013 Term: Chronic myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia
Conditions
Interventions
Product Name: WT1 TCR-transduced T cells
Pharmaceutical Form: Solution for infusion
Sponsors
Cell Medica Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: GENERAL INCLUSION CRITERIA All patients will undergo detailed laboratory based assessment prior to the procedure (Appendix A3). a) Age =18 years and =75 years. b) Life expectancy =16 weeks (4 months). c) World Health Organisation (WHO) performance status of 0-2 d) HLA A*0201 positive e) Completed previous course of chemotherapy = 4 weeks prior to commencing the initial phase of the trial (leucapheresis for collection of patient PBMC). f) Peripheral blood total lymphocyte count >0.5x109/L. g) Informed consent in writing and ability to co-operate with treatment and follow up. h) Willing, able and available for collection of PBMC/ T cells by leucapheresis. i) Hepatitis B and C, HTLV-1, Syphilis and HIV negative. j) Free from serious concurrent illness. k) 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. l) Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards. m) 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) 60 years; and (c) Poor Risk* AML in 1st CR (slow remitters and/or adverse cytogenetics). (2) 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)]. CHRONIC MYELOID LEUKAEMIA (CML): 1. Patients in chronic phase resistant to Glivec/Imatinib and 2nd generation tyrosine kinase inhibitors (eg., Dasatinib), AND NOT eligible for allogeneic BMT. 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. 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 leucapheresis and receiving TCR-transduced T cells. They will have monthly quantitative RT-PCR for Bcr-Abl and restart Glivec/Imatinib in the event of a log increase in transcript numbers.
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA a) Age 75 years. b) Patients should not receive concurrent systemic corticosteroids whilst on the study. c) Within three months of having received fludarabine (at time of leucapheresis). d) Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered. e) Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection. f) Patients with any other condition, which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial. g) Patients known to be serologically positive for Hepatitis B, C, HTLV-1, Syphilis or HIV. h) Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease i) Positive pregnancy test or reluctance to use contraception. j) Pregnant and lactating women are excluded. k) History of Severe Allergy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: SECONDARY OBJECTIVES 1) To determine the persistence and function of re-infused TCR-transduced T cells. 2) To document disease responses where possible. ; Main Objective: PRIMARY OBJECTIVES 1) To determine the feasibility of TCR gene transfer in a clinical setting. 2) To identify organ toxicities or other side effects related to the re-infusion of TCR-Transduced T cells. 3) Propose a safe dose of TCR-Transduced T cells for Phase II evaluation. ; Primary end point(s): PRIMARY ENDPOINTS AND OUTCOME MEASURES 1) Document transduction efficiency and TCR expression on TCR-transduced T cells. 2) Identify organ toxicities and other side effects. 3) Perform integration site analysis on TCR-transduced T cells. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Document WT1-specific immune responses of TCR-transduced T cells pre and post infusion. •Detect persistence of TCR-transduced T cells by Vß2.1 and tetramer staining and PCR for Vß2.1 and TCR-vector fragments. •Identification of disease response. | — |
Countries
United Kingdom
Contacts
Public ContactRegulatory Affairs
Cell Medica Ltd
Outcome results
None listed