A Phase 2 interventional study of Ponatinib and Azacitidine in CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE and CHRONIC MYELOGENOUS LEUKAEMIA IN MYELOID BLAST CRISIS, sponsored by Versailles Hospital. Completed at 29 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by Versailles Hospital · Phase 2, Interventional, and Treatment
This project is strategy aiming to improve the survival of patients with chronic myelogenous leukemia in advanced phase and myeloid blast crisis.
The basis of this strategy is to add the demethylating agent 5-Azacitidine to the tyrosine kinase inhibitor ponatinib and evaluate its activity in 2 cohorts of patients with either chronic myelogenous leukemia in advanced phase or myeloid blast crisis.
Versailles Hospital is the lead sponsor of 74 studies on the registry; 17 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patient with Philadelphia chromosome positive CML in first blast crisis or first accelerated phase:
AP-CML is defined by the presence of any of the following features:
Have adequate hepatic function as defined by the following criteria:
Exclusion Criteria:
Cardiovascular disease:
Patient with Philadelphia chromosome positive CML in accelerated phase is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), ≥ 20% basophils in PB or BM, ≥ 30% blasts plus promyelocytes (with blasts \<30%) in PB or BM, \<100 x109/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome);
Drug: Ponatinib · Drug: Azacitidine
Patient with Philadelphia chromosome positive CML in myeloid blast crisis is defined by the presence of ≥ 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.
Drug: Ponatinib · Drug: Azacitidine
Induction phase (first three cycles) \- ponatinib: 45 mg/day orally continuously Following the results of disease evaluation after 3 cycles: * Cohort A: AP-CML If a CHR and complete cytogenetic response are obtained after 3 months, ponatinib will be decreased at 30mg/day. If CHR and/or CCyR are not reached, ponatinib may be maintained at 45mg/day for another 3 cycles if decided by the investigator. * Cohort B: MBC-CML If a CHR is obtained during the induction phase, ponatinib daily dose will be reduced to 30 mg/day. If CHR is not reached, ponatinib may be maintained at 45mg/day for another 3 cycles if decided by the investigator. Maintenance therapy: Ponatinib will be decreased to 30 mg/day. During maintenance therapy, If a major molecular response is reached, ponatinib will be decreased to 15mg/day
Induction phase (first three cycles), Following the results of disease evaluation after 3 cycles and Maintenance therapy: \- 5-azacitidine : 75 mg/m² subcutaneously day 1 to day 7, every 4 weeks No dose modification of 5-Azacitidine is planned in both cohorts. Azacitidine may be stopped at 24 months in case of MR4 defined as 0.0032%\<MR4≤0.01%;
Overall Survival
To determine the overall survival of patients with AP-CML (cohort A) and MBC-CML (cohort-B) treated with the combination ponatinib and 5-azacitidine
Time frame: 2 years
safety of combination of ponatinib and 5-azacitidine
To determine the safety of combination ofponatinib and 5-azacitidine: number adverse events related to ponatinib assessed by CTCAE V4.0
Time frame: 1 year
rate of Complete Hematologic Response (CHR)
To assess the rate of CHR : number de patient in complete hematologic response
Time frame: 1 year
cytogenetic response
To assess the complete cytogenetic response by caryotype analysis
Time frame: 1 year
molecular response
To assess the major molecular responseby BCR-ABL IS quantification
Time frame: 1 year
rate of reversion to chronic phase CML
To assess the rate of reversion to chronic phase CML
Time frame: 1 year
duration of response
To estimate the duration of response
Time frame: 1 year
duration of event free survival
To estimate the duration of event-free survival
Time frame: 1 year
relationship between clinical efficacy and biological markers (mutations and methylation status
To investigate the relationship between clinical efficacy and biological markers: mutations and methylation status.
Time frame: 1 year
allogenic transplant
To estimate the rate of patients bridged to allogenic transplant
Time frame: 1 year
Survival after transplant
To follow up event-free survival after transplant
Time frame: 1 year
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Versailles Hospital