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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Emma
Morris
e.morris@ucl.ac.uk
Dr
Zahid
Sattar
zahid.sattar@ct.catapult.org.uk
Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
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This is a Phase I/II study to evaluate the safety and efficacy of the WT1 TCR therapy in patients with MDS or AML following azacitidine therapy. Myelodysplastic syndrome (MDS) is a chronic haematological disorder and the more severe forms of MDS are a precursor to acute myeloid leukaemia (AML). Azacitidine, a DNA hypomethylating agent, is now an established treatment strategy for more severe disease but Azacitidine is not curative and once patients no longer derive benefit, there is no established standard of care, and a median life expectancy of less than six months. Teams led by Prof. Emma Morris and Prof Hans Stauss from UCL developed a gene modified T cell receptor (TCR) which targets the WT1 antigen which is present at abnormally high levels on the surface of leukaemic and myelodysplastic cells. This generates T cells able to recognise WT1¬expressing target cells which are infused back into the patient to initiate an immune response specific to leukaemic tissue. In this trial, participants (approx. 45 screened for 25 evaluable) with an HLA¬A2 tissue type who have low blast count, stable MDS or AML but failed to reach an IWG response following Azacitidine therapy will be recruited. A leukapheresis sample will be taken and some of the patient’s own (autologous) T cells gene-modified using a GMP grade retroviral vector containing the genes for a WT1¬ specific, HLA¬A2 restricted T cell receptor. Following cell manufacture, the patients will receive a preparative lymphodepletion regimen and then an infusion of their modified cells. Patients will also receive low dose IL¬2 for 5 days post T cell infusion to further promote survival and proliferation of the infused T cells. Patient monitoring and follow-up for safety and efficacy of the infused cells will be carried out for at least 12 months.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
Interventional type: Cellular;Gene Therapy;
You can take part if:
You may not be able to take part if:
Subjects presenting with any of the following criteria will not be included in the trial: 1. Subjects who are in complete remission, partial remission, marrow complete remission or have a cytogenetic response or haematological improvement following azacitidine treatment (according to 2006 IWG) 2. Subjects with CMML who have a white blood cell count > 13 x 10E09/L 3. Subjects with peripheral blood total lymphocyte count <0.5 x 10E09/L 4. Subjects with acute promyelocytic leukaemia (FAB M3 Classification) 5. Subjects who are a candidate for allogeneic stem cell transplantation 6. Subjects requiring concurrent use of systemic steroids at time of leukapheresis or in a 14 day window around time of cell infusion 7. Subjects who have an immediate or anticipated need for induction chemotherapy, or are receiving decitabine and/or other agents that could confound the interpretation of trial results, in the opinion of the Investigator 8. Subjects with any active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast 9. Subjects with uncontrolled intercurrent illness including, but not limited to, clinically significant ischemic heart disease, cardiac arrhythmia, concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease, uncontrolled hypertension (defined as systolic pressure ≥160 mmHg and/or diastolic pressure ≥110 mmHg) or clinically significant pulmonary disease 10. Subjects with active infection (bacterial, viral or fungal) which is clinically significant at the time of leukapheresis or cell infusion 11. Subjects with known history of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) or who test positive for HTLV or Syphilis. Subjects who are positive for HIV, Hepatitis B or Hepatitis C must have a negative polymerase chain reaction (PCR) result prior to leukapheresis 12. Subjects with active auto-immune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Sjögren’s disease, sarcoidosis, vasculitis, polymyositis, psoriasis, relapsing polychondritis or glomerulonephritis) 13. Subjects with clinically significant non-hematologic toxicity after prior therapy chemotherapy higher than grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0) 14. Subjects with significant renal and liver parameters, as defined as total bilirubin ≥1.5mg/dL not related to haemolysis or Gilbert's disease; alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal (ULN) and/or serum creatinine ≥2.0 mg/dL 15. Subjects who require haemodialysis or peritoneal dialysis 16. Subject of childbearing potential unable to take adequate contraceptive precautions, has a positive pregnancy test result at screening, is otherwise known to be pregnant or is currently breastfeeding 17. Male subjects unwilling or unable to use adequate contraceptive precautions (barrier method or abstinence) at screening and throughout the trial 18. Subjects who have undergone major surgery without full recovery within last 28 days prior to screening 19. Subjects with known hypersensitivity to cyclophosphamide, fludarabine, methylprednisolone or IL-2 20. Subjects who have participated in any other interventional clinical trial or received treatment with any investigational agent, chemotherapy, or immunotherapy within 28 days prior to infusion. Growth factors and erythropoietin allowed before and during the trial as clinically indicated 21. Subjects who have received radiotherapy within 14 days prior to screening 22. Subject who has a severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
The study is sponsored by CELL MEDICA TCR LIMITED and funded by CELL THERAPY LIMITED .
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Read full details
for Trial ID: CPMS 19693
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