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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 46
- 主要终点
- Overall Survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •≥ 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
排除标准
- •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
研究组 & 干预措施
AP-CML
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);
干预措施: Ponatinib (Drug)
MBC-CML
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.
干预措施: Azacitidine (Drug)
MBC-CML
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.
干预措施: Ponatinib (Drug)
AP-CML
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);
干预措施: Azacitidine (Drug)
结局指标
主要结局
Overall Survival
时间窗: 2 years
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
次要结局
- rate of Complete Hematologic Response (CHR)(1 year)
- duration of response(1 year)
- relationship between clinical efficacy and biological markers (mutations and methylation status(1 year)
- allogenic transplant(1 year)
- Survival after transplant(1 year)
- safety of combination of ponatinib and 5-azacitidine(1 year)
- rate of reversion to chronic phase CML(1 year)
- cytogenetic response(1 year)
- molecular response(1 year)
- duration of event free survival(1 year)
研究者
Philippe ROUSSELOT
Clinical coordinator
Versailles Hospital