NCT03895671

Brief 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 either chronic myelogenous leukemia in advanced phase or myeloid blast crisis.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2019

Longer than P75 for phase_2

Geographic Reach
1 country

29 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 25, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 29, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

June 19, 2019

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2023

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2024

Completed
Last Updated

August 7, 2020

Status Verified

August 1, 2020

Enrollment Period

4.5 years

First QC Date

March 25, 2019

Last Update Submit

August 6, 2020

Conditions

CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASECHRONIC MYELOGENOUS LEUKAEMIA IN MYELOID BLAST CRISIS

Outcome Measures

Primary Outcomes (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

    2 years

Secondary Outcomes (10)

  • safety of combination of ponatinib and 5-azacitidine

    1 year

  • rate of Complete Hematologic Response (CHR)

    1 year

  • cytogenetic response

    1 year

  • molecular response

    1 year

  • rate of reversion to chronic phase CML

    1 year

  • +5 more secondary outcomes

Study Arms (2)

AP-CML

EXPERIMENTAL

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: PonatinibDrug: Azacitidine

MBC-CML

EXPERIMENTAL

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: PonatinibDrug: Azacitidine

Interventions

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

AP-CMLMBC-CML
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%;

AP-CMLMBC-CML

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • % blasts in peripheral blood (PB) or bone marrow (BM)
  • ≥ 20% basophils in PB
  • ≥ 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
  • +5 more criteria

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Centre Hospitalier Universitaire D'Amiens

Amiens, France

RECRUITING

Centre Hospitalier D'Avignon

Avignon, France

NOT YET RECRUITING

Centre Hospitalier de La Cote Basque

Bayonne, France

NOT YET RECRUITING

Hopital Avicenne

Bobigny, France

NOT YET RECRUITING

Institut Bergonie

Bordeaux, France

NOT YET RECRUITING

Centre Hospitalier de Caen-Normandie

Caen, France

NOT YET RECRUITING

Centre Hospitalier Metropole Savoie

Chambéry, France

RECRUITING

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, France

NOT YET RECRUITING

Hopital Henri Mondor

Créteil, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Dijon

Dijon, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Grenoble

Grenoble, France

RECRUITING

Hopital Bicetre

Le Kremlin-Bicêtre, France

NOT YET RECRUITING

Centre Hospitalier Regional Universitaire de Lille

Lille, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Limoges

Limoges, France

NOT YET RECRUITING

Centre Leon Berard

Lyon, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Nantes

Nantes, France

NOT YET RECRUITING

Hopital Pitie-Salpetriere

Paris, France

NOT YET RECRUITING

Hopital St Antoine

Paris, France

NOT YET RECRUITING

Hopital St Louis

Paris, France

RECRUITING

Centre Hospitalier de Perpignan

Perpignan, France

NOT YET RECRUITING

Hospices Civils de Lyon

Pierre-Bénite, France

NOT YET RECRUITING

Centre Hospitalier Annecy Genevois

Pringy, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Rennes

Rennes, France

NOT YET RECRUITING

Centre Henri Becquerel

Rouen, France

NOT YET RECRUITING

Centre Hospitalier de Strasbourg

Strasbourg, France

NOT YET RECRUITING

Institut Universitaire Du Cancer Toulouse

Toulouse, France

NOT YET RECRUITING

Chru de Nancy

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Centre Hospitalier de Versailles

Versailles, France

RECRUITING

Intitut Gustave Roussy

Villejuif, France

NOT YET RECRUITING

MeSH Terms

Interventions

ponatinibAzacitidine

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Central Study Contacts

Mélody FORT

CONTACT

+33139239776mfort@ch-versailles.fr

Laure Morisset

CONTACT

+33139239785lmorisset@ch-versailles.fr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical coordinator

Study Record Dates

First Submitted

March 25, 2019

First Posted

March 29, 2019

Study Start

June 19, 2019

Primary Completion

December 1, 2023

Study Completion

December 1, 2024

Last Updated

August 7, 2020

Record last verified: 2020-08

Locations

FR(29)