Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Blast Crisis

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Azacitidine

Ponatinib

Antimetabolites

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

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);

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.

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%;

Mélody FORT

Laure Morisset

Delphine LEBON

Harcène ZERAZHI

Frédéric BAUDUER

Thorsten BRAUN

Gabriel ETIENNE

Sylvain CHANTEPIE

Gian Matteo PICA

Eric HERMET

Lydia ROY

Marie-Lorraine CHRETIEN

Stéphane COURBY

Ali TURHAN

Bruno QUESNEL

Pascal TURLURE

Franck NICOLINI

Viviane DUBRUILLE

Madalina UZUNOV

Simona LAPUSAN

Emmanuel RAFFOUX

Fabienne VACHERET

Marie BALSAT

Pascale CONY-MAKHOUL

Martine ESCOFFRE- BARBE

Pascal LENAIN

Shanti NATARAJAN-AME

Suzanne TAVITIAN

Agnes GUERCI-BRESLER

Philippe ROUSSELOT

Stéphane DE BOTTON

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.

PONAZA : A COMBINATION OF PONATINIB AND 5-AZACITIDINE IN CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE OR IN MYELOID BLAST CRISIS

OPEN LABEL PHASE 2 STUDY ON THE EFFICACY AND TOLERANCE OF A COMBINATION OF PONATINIB AND 5-AZACITIDINE IN CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE OR IN MYELOID BLAST CRISIS - PONAZA TRIAL

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

To determine the safety of combination ofponatinib and 5-azacitidine: number adverse events related to ponatinib assessed by CTCAE V4.0

To assess the rate of CHR : number de patient in complete hematologic response

To assess the complete cytogenetic response by caryotype analysis

To assess the major molecular responseby BCR-ABL IS quantification

To assess the rate of reversion to chronic phase CML

To estimate the duration of event-free survival

To investigate the relationship between clinical efficacy and biological markers: mutations and methylation status.

To estimate the rate of patients bridged to allogenic transplant

To follow up event-free survival after transplant

Versailles Hospital

Clinical coordinator

Spots Global Cancer Trial Database for chronic myelogenous leukaemia in accelerated phase