Chronic myeloid Leukemia and acute myeloid leukemia in cytogentic remission
Conditions
Interventions
Product Name: pDOM-WT1-37 DNA Vaccine
Product Code: NA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pDOM-WT1-37 DNA vaccine
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: CML patients: Philadelphia chromosome positive CML in chronic phase, in complete cytogenetic response (CCyR) but with detectable BCR-ABL transcripts and maintained the CCyR on imatinib monotherapy for a minimum of 24 months. AML patients: WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi); All patients: • = 18 years of age, written informed consent. • Performance status of 0 or 1. • For vaccination groups: HLA-A0201 positive in at least one allele. • For control groups: HLA A2 negative in both alleles. • Renal function and liver function (Creatinine 1.0 x109/l; normal clotting. • Adequate venous access for repeated blood sampling according to protocol schedule. • If sexually active and possibly fertile, patients must agree to use appropriate contraceptive methods during the trial and for six months afterward. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients with CML: • CML in accelerated phase or blast crisis. • Imatinib dose modification in the previous year, imatinib interruption for more than 15 days in the previous 6 months to enrollment. • Prior interferon-a therapy. • having achieved complete molecular response (CMR) at any point during imatinib therapy. • hypocellular bone marrow (<20%). Patients with AML: • AML in haematological relapse or eligible for allogeneic SCT. • AML patients with the "good-risk" abnormalities comprised by the core binding factor leukaemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukemia with the translocation (15;17)). All patients: • Systemic steroids or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry. • Major surgery in the preceding three to four weeks from which the patient has not yet recovered. • Patients who are of high medical risk 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, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease. • Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study. • Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research questions are: a) In patients with chronic myeloid leukemia (CML) whether WT1 DNA vaccination can reduce the measurable amount of the leukaemia-derived marker (BCR-ABL and WT-1transcripts), of which BCR-ABL is already used for clinical monitoring of disease response and decision making. b) In patients with acute myeloid leukemia (AML) to examine the effect of WT1 DNA vaccination on time to disease progression in a patient group that has a 70% risk of disease recurrence in 2 years. ; Secondary Objective: The secondary research questions/objectives are: a) Whether we can stimulate the immune system successfully against the vaccine. We will measure this by evaluating immune responses to the WT1-gene segments encoded in the DNA vaccine. b) How the immune responses link to the clinical effect. c) Whether the immune cells can be detected in the skin of patients, when a small amount of WT1 epitope is given in a different form (peptide) in the skin. ; Primary end point(s): All analyses will be performed on an intention to treat basis. CML: the primary outcome is molecular response (major + minor; decrease in BCR-ABL transcript levels at two time-points during/following vaccination) measured at baseline (recruitment) and follow-up at 6, 12, 18 and 24 months. Fisher’s exact test will be used to compare difference in proportions of molecular response in CML patients versus controls. AML: the primary outcome is time to disease progression from date of consent to end of study participation for eligible patients. Median survival times and a Log-rank test will be computed to AML patients and their controls. The proportion surviving at 2 years will be compared between AML patient group and their controls using the Fisher’s exact test. | — |
Countries
United Kingdom
Outcome results
None listed