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

Launched by VERSAILLES HOSPITAL · Mar 27, 2019

Keywords

ClinConnect Summary

The PONAZA clinical trial is investigating a new treatment strategy for patients with advanced chronic myelogenous leukemia (CML), specifically those in a serious phase known as accelerated phase or myeloid blast crisis. This trial combines two medications: ponatinib, which targets specific cancer cells, and 5-azacitidine, which helps improve how the body responds to treatment. The goal is to see if this combination can help patients live longer and improve their overall health.

To be eligible for this trial, participants must be at least 18 years old and have a specific type of CML that meets certain criteria, such as having a high number of cancer cells in their blood or bone marrow. They should also be in decent overall health, meaning they can perform daily activities with some limitations. Participants will receive the study medications and be closely monitored by the research team throughout the trial. It's important to know that certain individuals, such as those who are pregnant or have specific heart conditions, cannot participate. This trial is currently recruiting participants, and those who join will be contributing to valuable research that could improve treatments for others facing similar health challenges.

Gender

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Eligibility criteria

• 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