A Phase II Study of the Combination of Decitabine, Venetoclax, and Ponatinib in Patients With Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase Chronic Myelogenous Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Overall response rate
研究概览
简要总结
This phase II trial studies how well the combination of decitabine, venetoclax, and ponatinib work for the treatment of Philadelphia chromosome-positive acute myeloid leukemia or myeloid blast phase or accelerated phase chronic myelogenous leukemia. Drugs used in chemotherapy such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine, venetoclax, and ponatinib may help to control Philadelphia chromosome-positive acute myeloid leukemia or myeloid blast phase or accelerated phase chronic myelogenous leukemia.
详细描述
PRIMARY OBJECTIVE:
I. To determine the efficacy of the regimen, as defined by the rate of complete remission (CR) or CR with incomplete count recovery (CRi).
SECONDARY OBJECTIVES:
I. To determine efficacy outcomes, including rate of minimal residual disease negativity by flow cytometry and polymerase chain reaction (PCR) for BCR-ABL1 transcripts, median relapse-free survival, and median overall survival.
II. To determine the proportion of patients proceeding to allogeneic stem cell transplant (ASCT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients with Philadelphia (Ph)+ acute myeloid leukemia (AML) or myeloid accelerated phase (AP)-chronic myelogenous leukemia (CML) or blast phase (BP)-CML (either t[9;22] and/or BCR-ABL1 positive by fluorescent in situ hybridization or polymerase chain reaction). Both untreated and relapsed/refractory patients are eligible
- •Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)
- •Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
- •Alanine aminotransferase (ALT) =< 1.5 x ULN, unless due to the underlying leukemia approved by the PI
- •Aspartate aminotransferase (AST) =< 1.5 x ULN unless due to the underlying leukemia approved by the PI
- •Creatinine clearance >= 30 mL/min
- •Serum lipase =< 1.5 x ULN
- •Amylase =< 1.5 x ULN
- •Ability to swallow
- •Signed informed consent
排除标准
- •Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
- •History of acute pancreatitis within 6 months of study or history of chronic pancreatitis
- •Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
- •Active secondary malignancy that in the investigator's opinion will shorten survival to less than 1 year
- •Active grade III-V cardiac failure as defined by the New York Heart Association criteria
- •Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- •Myocardial infarction (MI), stroke, revascularization, unstable angina or transient ischemic attack within 6 months
- •Left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment
- •Diagnosed or suspected congenital long QT syndrome
- •Clinically significant atrial or ventricular arrhythmias (such as uncontrolled, clinically significant atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes) as determined by the treating physician
- •Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 480 msec) unless corrected after electrolyte replacement
- •History of venous thromboembolism including deep venous thrombosis or pulmonary embolism within the past 3 months, excluding line-associated deep venous thrombosis (DVT) of the upper extremity
- •Uncontrolled hypertension (diastolic blood pressure > 100 mmHg; systolic > 150 mmHg)
- •Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
- •Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea, or a Food and Drug Administration (FDA)-approved BCR-ABL tyrosine kinase inhibitor (TKI) is permitted
- •Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception throughout the study period. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
研究组 & 干预措施
Treatment (ponatinib, venetoclax, decitabine)
See Detailed Description.
干预措施: Decitabine (Drug)
Treatment (ponatinib, venetoclax, decitabine)
See Detailed Description.
干预措施: Venetoclax (Drug)
Treatment (ponatinib, venetoclax, decitabine)
See Detailed Description.
干预措施: Ponatinib (Drug)
结局指标
主要结局
Overall response rate
时间窗: End of cycle 2 (each cycle is 28 days)
Defined as the proportion of patients achieving complete remission (CR) + CR with incomplete count recovery (CRi) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.
次要结局
- Proportion of patients proceeding to allogeneic stem cell transplant(Up to 4.5 years)
- Rate of minimal residual disease negativity(Up to 4.5 years)
- Relapse-free survival (RFS)(From the date of treatment initiation to the date of documented treatment relapses from CR/CRi or death from any cause, whichever occurs first, assessed up to 4.5 years)
- Overall survival (OS)(From treatment start till death or last follow-up, assessed up to 4.5 years)
- Incidence of adverse events(Up to 4.5 years)