E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic myeloid Leukemia and acute myeloid leukemia in cytogentic remission |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <1.5 x upper limit of normal, liver
function tests < 1.5 x upper limit of normal); Lymphocyte count > 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. |
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E.4 | Principal 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-α 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Randomization based on HLA A2 status |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Unvaccinated control group. |
|
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Provided in Protocol.
The trial will end with the submission of the definitive study report to the regulatory authorities. It is anticipated that the immunological evaluation will take longer than the clinical follow up. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |