A Phase II Study of Venetoclax in Combination With 10-day Oral Decitabine in Relapsed/Refractory Acute Myeloid Leukemia
概览
- 阶段
- 2 期
- 干预措施
- Decitabine and Cedazuridine
- 疾病 / 适应症
- Recurrent Acute Biphenotypic Leukemia
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
- 状态
- 进行中（未招募）
- 最后更新
- 17天前
概览
简要总结
This phase II trial studies the effects of venetoxlax in combination with decitabine and cedazuridine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as venetoclax and 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. Cedazuridine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving venetoxlax in combination with decitabine and cedazuridine may help to control acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVE: I. To determine the overall response rate (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], MLFS and partial response \[PR\]) of 10-days decitabine and cedazuridine (oral decitabine) and venetoclax in patients with refractory/relapsed acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To determine the duration of response, event-free survival (EFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination. II. To determine the number of patients who achieve a hematologic improvement (HI) in platelets, hemoglobin, or ANC and the number of patients who achieve \> 50% reduction in blasts on therapy with venetoclax/10-day oral decitabine. III. To determine the safety of venetoclax in combination with 10-day oral decitabine in patients with refractory/ relapsed AML. IV. To determine the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day oral decitabine regimen. V. To determine the incidence of infectious complications per cycle with venetoclax in combination with 10-day oral decitabine. EXPLORATORY OBJECTIVE: I. To investigate global gene expression profiles, cytometry by time of flight (CyTOF), BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment. OUTLINE: Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
研究者
入排标准
入选标准
- •Patients with a diagnosis of relapsed or refractory AML (or biphenotypic or bilineage leukemia including a myeloid component). Patients with isolated extramedullary AML are eligible
- •Age \>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Creatinine \< 2 unless related to the disease
- •Direct bilirubin \< 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \< 3 x ULN unless considered due to leukemic involvement
- •In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. Oral hydroxyurea and/or cytarabine (up to 2 g/m\^2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
- •Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug
- •Willing and able to provide informed consent
排除标准
- •Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
- •Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI)
- •Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications as determined by the investigator
- •Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia
- •Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
- •Known active hepatitis B (HBV) or hepatitis C (HCV) infection or known human immunodeficiency virus (HIV) infection
- •Subject has a white blood cell count \> 10 x 10\^9/L. (Note: Hydroxyurea is permitted to meet this criterion)
- •Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
- •Nursing women, women of childbearing potential (WOCBP) with positive urine or serum pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception
- •Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)
研究组 & 干预措施
Treatment (decitabine and cedazuridine, venetoclax)
Patients receive decitabine and cedazuridine PO QD on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Decitabine and Cedazuridine
Treatment (decitabine and cedazuridine, venetoclax)
Patients receive decitabine and cedazuridine PO QD on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Venetoclax
结局指标
主要结局
Overall response rate (ORR)
时间窗: Within 4 cycles of treatment (each cycle is 28 days)
Defined as the proportion of patients who had complete remission (CR), complete remission with incomplete count recovery (CRi), partial response (PR) or MLFS. Will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval.
Incidence of adverse events
时间窗: Up to 2 years
The overall incidence and severity of all adverse events using Common Toxicity Criteria version 5.0. Safety data will be summarized using frequency and percentage, by category and severity.
次要结局
- Number of patients who transition towards stem cell transplantation(Up to 2 years)
- Incidence of infectious complications(Up to 2 years)
- Event-free survival (EFS)(Time interval between treatment start until disease progression, relapse/refractory, or death due to any cause, assessed up to 2 years)
- Proportion of achieving HI(Up to 2 years)
- Overall survival (OS)(Time interval between treatment start until death due to any cause, assessed up to 2 years)
- Duration of response(Time from response till progression, relapse/refractory, or death, assessed up to 2 years)
- Gene expression profiles(Up to 2 years)