Acute Myeloid Leukaemia and Myelodysplastic Syndromes in adults MedDRA version: 20.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: WT1 TCR Transduced T Cells
Product Code: D-00272
Pharmaceutical Form: Solution for injection/infusion
Sponsors
Cell Medica Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial: Diagnosis and main criteria for admission to screening phase of trial: The trial will recruit subjects with MDS or AML who have received hypomethylating agent therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine), and are EITHER: • Relapsed, defined as failing to maintain an initial IWG response OR • Stable, defined as failing to achieve an IWG response IWG response is defined as complete remission; partial remission; marrow complete remission; cytogenetic response; stable disease with haematological improvement. Subjects who have received hypomethylating agent therapy as part of a combination regimen may be eligible after discussion with the Sponsor. 1. Subjects aged 18 years or older who have a diagnosis of, EITHER: • MDS with an IPSS of intermediate -2, or high and one of the following FAB types: o Refractory anaemia with excess blasts (RAEB) o Chronic myelomonocytic leukaemia (CMML) with at least 10% bone marrow blasts (WHO CMML II) OR • AML (diagnosed according to WHO classification 2008 revision) 2. Subjects with documented HLA-A*0201 positive serotype 3. Subjects with less than 30 per cent bone marrow blasts 4. Subjects with relapsed disease must have less than 5 per cent peripheral blasts 5. Subjects with stable disease must have less than 10 per cent peripheral blasts 6. Subjects with less than a doubling of bone marrow blast count between the start of hypomethylating agent therapy and the date of screening 7. Subjects to complete screen 1 visit within a minimum of 28 days and maximum of 90 days since completion of azacitidine or decitabine therapy. Subjects who have exceeded the 90 day window may be eligible after discussion with the Sponsor. 8. Subjects with ECOG status 0, 1 or 2 9. Subjects who have at least one cytopenia (ANC =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following criteria will not be included in the trial: 1. Subjects with CMML who have a white blood cell count >13000 million / L 2. Subjects with peripheral blood total lymphocyte count < 500 million / L 3. Subjects with acute promyelocytic leukaemia (FAB M3 Classification) 4. Subjects who are a current candidate for allogeneic stem cell transplantation and have a suitable donor 5. Subjects requiring concurrent use of systemic steroids at time of leukapheresis or in a 14 day window around time of cell infusion 6. Subjects who have an immediate or anticipated need for induction chemotherapy, or are receiving agents that could confound the interpretation of trial results, in the opinion of the Investigator 7. Subjects with any active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast 8. Subjects with uncontrolled intercurrent illness including, but not limited to, clinically significant ischaemic 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 9. Subjects with active infection (bacterial, viral or fungal) which is clinically significant at the time of leukapheresis or cell infusion 10. 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 11. Subjects with active auto-immune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Sjögren’s syndrome, sarcoidosis, vasculitis, polymyositis, psoriasis, relapsing polychondritis or glomerulonephritis) 12. Subjects with clinically significant non-haematologic toxicity after prior chemotherapy higher than grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0) 13. Subjects with clinically significant renal and liver parameters, defined as total bilirubin =1.5 mg/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 14. Subjects who require haemodialysis or peritoneal dialysis 15. 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 breast-feeding 16. Male subjects unwilling or unable to use adequate contraceptive precautions (barrier method or abstinence) at screening and throughout the trial 17. Subjects who have undergone major surgery without full recovery within last 28 days prior to screening 18. Subjects with known hypersensitivity to fludarabine, methylprednisolone or IL-2 19. 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 20. Subjects who have received previous treatment with gene modified T cell therapy 21. Subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety and proportion of subjects achieving one or more IWG (2006) response criteria (within 12 months) following gene-modified WT1 TCR therapy ;Secondary Objective: • To examine the safety and tolerability of gene-modified WT1 TCR therapy • To evaluate the clinical efficacy of gene-modified WT1 TCR therapy • To confirm the technical feasibility of gene-modified WT1 TCR therapy in subjects with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) with low blast count • To determine the persistence and function of WT1 TCR-transduced T cells;Primary end point(s): Efficacy Proportion of subjects achieving one or more of the following IWG response criteria within 12 months of administration of gene-modified WT1 TCR T cell therapy: complete remission; partial remission; marrow complete remission; cytogenetic response; haematological improvement Safety Suspected Unexpected Serious Adverse reactions ;Timepoint(s) of evaluation of this end point: Efficacy Within 12 months of administration of gene-modified WT1 TCR T cell therapy Safety 12 months after each patient recieves last dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • Proportion of subjects achieving a Haematological Improvement (HI): 1. Erythroid response 2. Platelet response 3. Neutrophil response • Overall Remission Rate (complete remission & partial remission) • Proportion of subjects achieving marrow complete remission • Proportion of subjects achieving complete or partial cytogenetic response • Proportion of subjects achieving a molecular response • Proportion of subjects achieving IWG defined response of stable disease and duration of stable disease • Proportion of subjects with MDS transforming to AML and time to AML transformation • Progression Free Survival (PFS) • Event Free Survival (EFS) • Overall Survival (OS) Safety • Adverse events (AEs) • Clinical laboratory parameters • Tolerability ;Timepoint(s) of evaluation of this end point: Efficacy Within 12 months of administration of gene-modified WT1 TCR T cell therapy Safety 12 months after each patient recieves last dose 5 years follow up will also apply outside of trial | — |
Countries
Belgium, Germany
Contacts
Public ContactAlex BLoom
Cell Medica Ltd
Outcome results
None listed