WT1 immunity via DNA vaccination in haematological malignancies by intramuscular injection and electroporatio
- Conditions
- Topic: National Cancer Research NetworkSubtopic: Haematological OncologyDisease: Leukaemia (acute), Leukaemia (chronic), Leukaemia (acute myeloid), Leukaemia (acute lymphoblastic), Leukaemia (acute promyelocytic)CancerLeukaemia
- Registration Number
- ISRCTN62678383
- Lead Sponsor
- Southampton University Hospitals NHS Trust (UK)
- Brief Summary
2016 Results article in https://www.ncbi.nlm.nih.gov/pubmed/27099895 results
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 21
Current inclusion criteria as of 02/07/2012
1. CML group:
1.1. Philadelphia chromosome positive CML in chronic phase
1.2. In complete cytogenetic response (CCyR) but with detectable BCR-ABL transcripts and maintained the CCyR on Imatinib monotherapy for a minimum of 24 months
2. AML group:
2.1. WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi)
As the vast majority of AML express WT and evaluation in CR or CRi is technically not feasible, formal demonstration of WT1 expression in AML cells is not required. Where historical or relapsed samples become available, WT1 expression status will be evaluated post hoc.
3. All patients:
3.1. = 18 years of age, written informed consent
3.2. Performance status of 0 or 1.
3.3. for vaccination groups: HLA-A0201 positive in at least one allele
3.4. for control groups: HLA A2 negative in both alleles
3.5. 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
3.6. HB>100 g/l
3.7. Adequate venous access for repeated blood sampling according to protocol schedule.
3.8. If sexually active and possibly fertile, patients must agree to use appropriate contraceptive methods during the trial and for six months afterwards.
* If the lymphocyte count is below 1.0 at the time of entry into the trial but has been over 1.0 in the last 6 months and has also not declined rapidly in the days and weeks preceding entry, then the patient is eligible.
Previous inclusion criteria
1. CML group:
1.1. Philadelphia chromosome positive CML in chronic phase
1.2. In complete cytogenetic response (CCyR) but with detectable BCR-ABL transcripts and maintained the CCyR on Imatinib monotherapy for a minimum of 24 months
2. AML group:
2.1. WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi)
As the vast majority of AML express WT and evaluation in CR or CRi is technically not feasible, formal demonstration of WT1 expression in AML cells is not required. Where historical or relapsed samples become available, WT1 expression status will be evaluated post hoc.
3. All patients:
3.1. Male and female, lower age limit of 18 years
3.2. Written informed consent
3.3. Performance status of 0 or 1
3.4. For vaccination groups: HLA-A0201 positive in at least one allele
3.5. For control groups: HLA A2 negative in both alleles
3.6. Renal function and liver function (creatinine less than 1.5 x upper limit of normal, liver function tests less than 1.5 x upper limit of normal); lymphocyte count greater than 1.0 x 10^9/l; normal clotting
3.7. HB greater than 100 g/l
3.8. Adequate venous access for repeated blood sampling according to protocol schedule
3.9. If sexually active and possibly fertile, patients must agree to use appropriate contraceptive methods during the trial and for six months afterwards
Previous inclusion criteria
1. CML patients:
1.1. CML in accelerated phase or blast crisis or having achieved CMR at any point during imatinib therapy
1.2. Imatinib dose modification in the previous year, imatinib interruption for more than 15 days in the previous 6 months to enrolment
1.3. Prior interferon-a therapy
1.4. Hypocellular bone marrow (less than 20%) (indicated by blood counts and most recent bone marrow (where available)
1.5. Complete molecular response (CMR)
2. AML patients:
2.1. AML in haematological relapse or eligible for allogeneic SCT
2.2. Hypocellular bone marrow (less than 20%)
2.3. 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 leukaemia with the translocation [15;17])
3. 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
?HB>100 g/l
?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 afterwards.
* If the lymphocyte count is below 1.0 at the time of entry into the trial but has been over 1.0 in the last 6 months and has also not declined rapidly in the days and weeks preceding entry, then the patient is eligible.
Previous exclusion criteria as of 22/12/2011
1. CML patients:
1.1. CML in accelerated phase or blast crisis or having achieved CMR at any point during imatinib therapy
1.2. Imatinib dose modification in the previous year, imatinib interruption for more than 15 days in the previous 6 months to enrolment
1.3. Prior interferon-a therapy
1.4. Hypocellular bone marrow (less than 20%) (indicated by blood counts and most recent bone marrow (where available)
1.5. Complete molecular response (CMR)
2. AML patients:
2.1. AML in haematological relapse or eligible for allogeneic SCT
2.2. Hypocellular bone marrow (less than 20%)
2.3. 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 leukaemia with the translocation [15;17])
3. All patients:
3.1. 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
3.2. Major surgery in the preceding three to four weeks from which the patient has not yet recovered
3.3. Patients who are of high medical risk because of non-malignant systemic
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. CML: Molecular response of BCR-ABL transcripts, measured at any time during follow up<br> 2. AML: time to disease progression<br>
- Secondary Outcome Measures
Name Time Method <br> 1. AML: 2-year survival, overall survival, measured at any point during follow up<br> 2. AML: Time to disease progression, measured at any point during follow up<br> 3. Molecular response of WT1 transcripts, measured at any point during follow up<br>