A study to assess the safety and immunogenicity of an anti leukemia Antigen-Specific Cancer Immunotherapeutic (ASCI) combined with infusions of T lymphocytes in in vivo regulatory T cells depleted patients as post-consolidation therapy for adult patients with WT1-positive Acute Myeloid Leukemia (AML).
- Conditions
- For adult patients with WT1-positive Acute Myeloid Leukemia (AML) in CR1 (for high risk patients) or in CR2 or CR3 who are not eligible for allogeneic stem cell transplantation (SCT)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2011-004144-22-BE
- Lead Sponsor
- Institut Jules Bordet - Université Libre de Bruxelles
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
The following criteria are to be checked at the time of study entry. Patients may only be included in the study if all of the following criteria are met:
1. The patient has cytologically proven AML, as defined by the WHO classification. The leukemia is a de novo or a secondary leukemia.
2. The patient received the following therapy according to the institution’s standard of care:
•For patients = 60 years old, at least two cycles of intensive chemotherapy (induction and consolidation)
•For patients > 60 years old, at least one induction chemotherapy. Any patients with severe co-morbidity for which consolidation is unacceptable, can receive only one induction therapy.
3. The patient is in complete morphologic remission, as detailed in Appendix G
a)AML patients in first complete remission (CR1) who are not eligible for allo-HSCT following the institution’s standard of care, except the favourable genetic group subset as defined in Table 1 below which is excluded from this study.
According to the EBMT treatment consensus: favourable risk group AML patients should not be transplanted upfront, whilst high and intermediate-II risk group patients should be transplanted as first treatment option (The EBMT handbook 5th edition, 2008). The benefit of transplant for the intermediate group-I is still an open question and a center decision.
b)All AML patients in second or third complete morphological remission (CR2 or CR3) according to response criteria who are not eligible for allo-SCT.
4. The patient's blasts cells show over-expression of WT1 transcripts, detected in peripheral blood by qRT-PCR at diagnosis or in first relapse.
Note: WT1 expression analysis will be done using peripheral blood obtained before chemotherapy.
5. Written informed consent has been obtained prior to the performance of any protocol-specific procedure.
6. The patient is = 18 years of age at the time of signing of the ICF.
7. ECOG performance status of 0, 1, or 2 at the time of enrolment.
8. Adequate hepatic and renal function defined as:
- Serum bilirubin < 1.5 times the Upper Limit of Normal (ULN).
- Serum alanine aminotransferase ALAT < 2.5 times the ULN.
- Calculated creatinine clearance > 40 mL/min.
9. If the patient is female, then she must be of non-childbearing potential, i.e., have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to treatment administration, have a negative pregnancy test, and continue such precautions for two months after completion of the treatment administration series.
10. Under the investigator criteria, the patient is able to comply with the protocol requirements during the duration of the study.
11. In the investigator's opinion and in compliance with the Institution hematology guidance, the patient should not be eligible for an approved standard of care such as induction with chemotherapy or allo-HSCT.
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 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13
The following criteria should be checked at the time of study entry. If any are met, then the patient must not be included in the study:
1. The patient is in morphologic leukemia-free state or in morphologic complete remission but with incomplete blood count recovery as defined by IWG Response Criteria (Appendix G)
2. The patient is in CR1 and is in the category of low-risk for relapse patients, i.e. belong to the favourable genetic group subset (as described in table 1).
3. The patient was diagnosed with leukemic central nervous system (CNS) disease (E.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement.
4. The patient has received, is receiving (or is due to receive) allogeneic HSCT.
5. The patient has concomitant malignancies, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
6. The patient is known to be human immunodeficiency virus positive.
7. The patient has autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis and inflammatory bowel disease.
8. The patient has a history of allergic reactions likely to be exacerbated by any component of the study investigational product.
9. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
10. The patient has congestive heart failure, symptomatic coronary artery disease, or previous myocardial infarction.
11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.
12. The patient has received any investigational or non-registered medicinal product other than the study medication within 30 days preceding the first dose of study medication, or plans to receive such a drug during the study period.
13. The patient requires concomitant treatment with systemic corticosteroids or any immunosuppressive agents. The use of inhaled corticosteroids or topical steroids is permitted.
14. The patient has an active infection and/or is receiving antibiotics. Enrolment will be allowed 48h00 after the end of the treatment.
15. For female patients: the patient is pregnant or lactating.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method