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CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASEPhase 2PONAZANCT03895671

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

A Phase 2 study testing Ponatinib and Azacitidine in people with CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE and CHRONIC MYELOGENOUS LEUKAEMIA IN MYELOID BLAST CRISIS, run by Versailles Hospital at 29 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ponatinib and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
29 sitesFrance
Study dates
19 Jun 2019to 31 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient aged 18 years or more
  • Signed informed consent
  • 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:
  • 15-29% blasts in peripheral blood (PB) or bone marrow (BM)
  • ≥ 20% basophils in PB
Show all 20Show fewer
  • ≥ 30% blasts plus promyelocytes (with blasts <30%) in PB or BM,
  • <100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome);
  • MBC-CML is defined by the presence of ≥ 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3
  • Have adequate renal function as defined by the following criterion: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) for institution
  • Have adequate hepatic function as defined by the following criteria:
  • Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome or CML
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present
  • Have normal pancreatic status as defined by the following criterion: Serum lipase and amylase ≤ 1.5 × ULN
  • Have normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
  • Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
  • Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile).
  • Have fully recovered (≤ grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug

Who cannot join

  • Pregnant or lactating women,
  • Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment,
  • Prior history of hematopoietic stem cell transplantation
  • Cardiovascular disease:
  • Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure.
  • Myocardial infarction within the previous 6 months
Show all 12Show fewer
  • Symptomatic cardiac arrhythmia requiring treatment
  • Individuals with another active malignancy
  • Patients at high risk or very high risk of arterio-veinous occlusive disease defined by European CVD score
  • Previous treatment with azacitidine,
  • Diagnosis of malignant disease within the previous 12 months (excluding base cell carcinoma, "in-situ" carcinoma of the cervix or breast or other local malignancy excised or irradiated with a high probability of cure)
  • Known active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

France29 sites

  • Centre Hospitalier Universitaire D'Amiens

    Amiens

  • Centre Hospitalier D'Avignon

    Avignon

  • Centre Hospitalier de La Cote Basque

    Bayonne

  • Hopital Avicenne

    Bobigny

  • Institut Bergonie

    Bordeaux

  • Centre Hospitalier de Caen-Normandie

    Caen

  • Centre Hospitalier Metropole Savoie

    Chambéry

  • Centre Hospitalier Universitaire de Clermont Ferrand

    Clermont-Ferrand

  • Hopital Henri Mondor

    Créteil

  • Centre Hospitalier Universitaire de Dijon

    Dijon

  • Centre Hospitalier Universitaire de Grenoble

    Grenoble

  • Hopital Bicetre

    Le Kremlin-Bicêtre

  • Centre Hospitalier Regional Universitaire de Lille

    Lille

  • Centre Hospitalier Universitaire de Limoges

    Limoges

  • Centre Leon Berard

    Lyon

  • Centre Hospitalier Universitaire de Nantes

    Nantes

  • Hopital Pitie-Salpetriere

    Paris

  • Hopital St Antoine

    Paris

  • Hopital St Louis

    Paris

  • Centre Hospitalier de Perpignan

    Perpignan

  • Hospices Civils de Lyon

    Pierre-Bénite

  • Centre Hospitalier Annecy Genevois

    Pringy

  • Centre Hospitalier Universitaire de Rennes

    Rennes

  • Centre Henri Becquerel

    Rouen

  • Centre Hospitalier de Strasbourg

    Strasbourg

  • Institut Universitaire Du Cancer Toulouse

    Toulouse

  • Chru de Nancy

    Vandœuvre-lès-Nancy

  • Centre Hospitalier de Versailles

    Versailles

  • Intitut Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: 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

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.

Being tested
Ponatinib, Azacitidine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PonatinibDrug

    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

  • AzacitidineDrug

    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%;

Study groups in NCT03895671
Study groupRoleWhat they receive
AP-CMLExperimentalPatient 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);
Receives: Drug: Ponatinib; Drug: Azacitidine
MBC-CMLExperimentalPatient 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.
Receives: Drug: Ponatinib; Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 2 years

Secondary outcomes (10)

  1. 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

    Measured: 1 year

  2. rate of Complete Hematologic Response (CHR)

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

    Measured: 1 year

  3. cytogenetic response

    To assess the complete cytogenetic response by caryotype analysis

    Measured: 1 year

  4. molecular response

    To assess the major molecular responseby BCR-ABL IS quantification

    Measured: 1 year

  5. rate of reversion to chronic phase CML

    To assess the rate of reversion to chronic phase CML

    Measured: 1 year

  6. duration of response

    To estimate the duration of response

    Measured: 1 year

  7. duration of event free survival

    To estimate the duration of event-free survival

    Measured: 1 year

  8. 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.

    Measured: 1 year

  9. allogenic transplant

    To estimate the rate of patients bridged to allogenic transplant

    Measured: 1 year

  10. Survival after transplant

    To follow up event-free survival after transplant

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2019
  2. Study start19 Jun 2019
  3. Primary completion31 Aug 2025
  4. Study completion31 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03895671
Sponsor's protocol ID
P16/23 PONAZA
Acronym
PONAZA
Status last verified
Feb 2024
First submitted
25 Mar 2019
Last updated
6 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib and Azacitidine in people with CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE and CHRONIC MYELOGENOUS LEUKAEMIA IN MYELOID BLAST CRISIS, run by Versailles Hospital at 29 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03895671.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.

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