CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE Clinical Trial
— PONAZAOfficial 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.
| Status | Recruiting |
| Enrollment | 40 |
| Est. completion date | December 1, 2024 |
| Est. primary completion date | December 1, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Patient aged 18 years or more 2. Signed informed consent 3. 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 - = 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. 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3 5. Have adequate renal function as defined by the following criterion: Serum creatinine = 1.5 × upper limit of normal (ULN) for institution 6. Have adequate hepatic function as defined by the following criteria: 1. Total serum bilirubin = 1.5 × ULN, unless due to Gilbert's syndrome or CML 2. Alanine aminotransferase (ALT) = 2.5 × ULN, or = 5 × ULN if leukemic infiltration of the liver is present 3. Aspartate aminotransferase (AST) = 2.5 × ULN, or = 5 × ULN if leukemic infiltration of the liver is present 7. Have normal pancreatic status as defined by the following criterion: Serum lipase and amylase = 1.5 × ULN 8. Have normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females. 9. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential). 10. Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile). 11. Have fully recovered (= grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug Exclusion Criteria: 1. Pregnant or lactating women, 2. Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment, 3. Prior history of hematopoietic stem cell transplantation 4. 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 5. Individuals with another active malignancy 6. Patients at high risk or very high risk of arterio-veinous occlusive disease defined by European CVD score 7. Previous treatment with azacitidine, 8. 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) 9. Known active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C |
| Country | Name | City | State |
|---|---|---|---|
| France | Centre Hospitalier Universitaire D'Amiens | Amiens | |
| France | Centre Hospitalier D'Avignon | Avignon | |
| France | Centre Hospitalier de La Cote Basque | Bayonne | |
| France | Hopital Avicenne | Bobigny | |
| France | Institut Bergonie | Bordeaux | |
| France | Centre Hospitalier de Caen-Normandie | Caen | |
| France | Centre Hospitalier Metropole Savoie | Chambéry | |
| France | Centre Hospitalier Universitaire de Clermont Ferrand | Clermont-Ferrand | |
| France | Hopital Henri Mondor | Créteil | |
| France | Centre Hospitalier Universitaire de Dijon | Dijon | |
| France | Centre Hospitalier Universitaire de Grenoble | Grenoble | |
| France | Hopital Bicetre | Le Kremlin-Bicêtre | |
| France | Centre Hospitalier Regional Universitaire de Lille | Lille | |
| France | Centre Hospitalier Universitaire de Limoges | Limoges | |
| France | Centre Leon Berard | Lyon | |
| France | Centre Hospitalier Universitaire de Nantes | Nantes | |
| France | Hopital Pitie-Salpetriere | Paris | |
| France | Hopital St Antoine | Paris | |
| France | Hopital St Louis | Paris | |
| France | Centre Hospitalier de Perpignan | Perpignan | |
| France | Hospices Civils de Lyon | Pierre-Bénite | |
| France | Centre Hospitalier Annecy Genevois | Pringy | |
| France | Centre Hospitalier Universitaire de Rennes | Rennes | |
| France | Centre Henri Becquerel | Rouen | |
| France | Centre Hospitalier de Strasbourg | Strasbourg | |
| France | Institut Universitaire Du Cancer Toulouse | Toulouse | |
| France | Chru de Nancy | Vandœuvre-lès-Nancy | |
| France | Centre Hospitalier de Versailles | Versailles | |
| France | Intitut Gustave Roussy | Villejuif |
| Lead Sponsor | Collaborator |
|---|---|
| Versailles Hospital |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 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 | 1 year | |
| Secondary | rate of Complete Hematologic Response (CHR) | To assess the rate of CHR : number de patient in complete hematologic response | 1 year | |
| Secondary | cytogenetic response | To assess the complete cytogenetic response by caryotype analysis | 1 year | |
| Secondary | molecular response | To assess the major molecular responseby BCR-ABL IS quantification | 1 year | |
| Secondary | rate of reversion to chronic phase CML | To assess the rate of reversion to chronic phase CML | 1 year | |
| Secondary | duration of response | To estimate the duration of response | 1 year | |
| Secondary | duration of event free survival | To estimate the duration of event-free survival | 1 year | |
| Secondary | 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. | 1 year | |
| Secondary | allogenic transplant | To estimate the rate of patients bridged to allogenic transplant | 1 year | |
| Secondary | Survival after transplant | To follow up event-free survival after transplant | 1 year |