AML, MDS
Conditions
Keywords
Very high risk MDS, AML, ASTX727, DLI
Brief summary
Study of early administration of ASTX727 associated with late Donor Lymphocyte Infusions after allogenic stem cell transplantation in very high risk MDS or AML patients
Detailed description
Prospective study of early administration of ASTX727 associated with late Donor Lymphocyte Infusions after allogenic stem cell transplantation in very high risk MDS or AML patients
Interventions
DRUGASTX727
Eligible patient started ASTX727 between 40 and 130 days after allogenic stem cell transplantation
In absence of previous grade 2-4 or chronic graft-versus-host disease (GVHD), DLI will be administered at increasing doses the first day of ASTX727 cycles
Sponsors
Astex Pharmaceuticals, Inc.
Groupe Francophone des Myelodysplasies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged from 18 to 70 years * MDS or AML with unfavorable genetics defined as follow: * 4 or more cytogenetic abnormalities or * 3 cytogenetic abnormalities and TP53 or other unfavorable mutations (ASXL1, RUNX1) or * 3 cytogenetic abnormalities and monosomal karyotype or * mutations involving EVI1 * AML patients should have received chemotherapy * Marrow blast \< 20% for MDS and \< 10% for AML post chemotherapy * For MDS : Revised IPSS poor or very poor ; For AML : ELN adverse risk * Non-proliferative disease * A donor is available (HLA matched or mismatched) * Adequate contraception in women \< 50 years and for men. Subjects must agree to use, and to be able to comply with, effective contraception without interruption, at least the first six months after transplant, throughout the entire duration of study drug therapy and for at least 6 months for women and 3 months for men after the last dose of study drug therapy.
Exclusion criteria
* ECOG 3 or more * Cancer less than 2 years before inclusion or cancer not in remission the last 2 years before inclusion (except in situ cancer or baso cellular cancer) * Cardiac failure with Ejection Fraction \< 50% * Creatininemia level \> 150 µmol/L * Liver enzyme \> 3 N * Conjugated bilirubinemia \> 25 µmol/L * MDS occurring in patients with Fanconi anemia or congenital dyskeratosis * Proliferative disease in patients not in remission: White Blood Cell (WBC) \> 15 G/L or use of continuous cytotoxic to maintain WBC \< 15 G/L * AML with marrow or peripheral blast count higher than 10% after chemotherapy * Known allergy or hypersensitivity to the investigational agent or decitabine or its metabolites or formulation excipients * No contraception * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease free Survival (DFS) at one year post transplant | 1 year post transplant | Measure of time during which no sign of progression is found |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) at one year post transplant | 1 year post transplant | Measure of time from randomization to death from any cause |
| Overall Survival (OS) at two years post transplant | 2 years post transplant | Measure of time from randomization to death from any cause |
| Risk factors for DFS, OS and non-relapse mortality at 1 and 2 years | 1 and 2 years | Statistical study of cumulative incidence curves |
Countries
France
Outcome results
None listed