NCT03573024已完成2 期
Safety and Efficacy of Venetoclax and Azacitidine for Newly Diagnosed Non-Elderly Adult Patients (Aged 18-59) With Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Response Rate, measured by the European Leukemia Net definition: (CRMRD-+CR+CRi+MLFS)
研究概览
简要总结
This study aims to treat non-elderly adult patients, who were previously untreated for acute myeloid leukemia, using venetoclax and azacitidine.
详细描述
This is a phase II study that seeks to treat patients ages 18-59 who have acute myeloid leukemia but have never been treated before. It will use venetoclax and azacitidine, and patients can receive up to four cycles of this medication. Depending on the level of recovery, patients will either be forced to come off study or have the option to continue the medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.
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 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A subject will be eligible for study participation if he/she meets the following criteria within 28 days prior to the first day of therapy (bone marrow biopsy can be performed 28 days prior to the first day of therapy). Historical records are permitted per Investigator discretion.
- •Subject must have confirmation of non-APL and AML by WHO criteria45
- •Subject must have received no prior treatment for AML
- •Age ≥18 years, ≤59 years
- •Without clinical signs of active central nervous system disease
- •Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
- •Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
- •Subject must have adequate liver function as demonstrated by:
- •aspartate aminotransferase (AST) ≤ 3.0 × ULN*
- •alanine aminotransferase (ALT) ≤ 3.0 × ULN*
- •bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome* * Unless considered due to leukemic organ involvement
- •Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
- •Female subjects who are pre-menopausal and have not had a hysterectomy or oophorectomy must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting therapy; 2) throughout the entire duration of treatment; 3) during dose interruptions; and 4) for at least 90 days after discontinuation of therapy (last dose of study drug).
- •Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed screening procedures.
- •Subject must have adverse risk disease as defined by the European LeukemiaNet46 (Appendix B) 5.3.2
排除标准
- •A subject will not be eligible for study participation if he/she meets any of the following criteria:
- •Subject has received disease modifying treatment for myelodysplastic syndrome (MDS) or AML. ATRA given for clinical suspicion of APL will not be exclusionary and no washout will be required in this scenario.
- •Subject is known to be positive for HIV. HIV testing is not required.
- •Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, anti-HBs+ and anti-HBc-) may participate
- •Subject has received within 7 days prior to the first dose of study drug:steroid therapy for anti-neoplastic intent; strong and moderate CYP3A inhibitors; strong and moderate CYP3A inducers.
- •Subject is informed that consumption of the following fruits is prohibited 3 days prior to the initiation of study treatment and throughout participation: grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit.
- •Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
- •New York Heart Association heart failure > class 2
- •Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia
- •Subject has a malabsorption syndrome or other condition that precludes enteral route of administration
- •Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
- •Subject has a history of other malignancies prior to study entry, with the exception of:
- •Adequately treated in situ carcinoma of the breast or cervix uteri
- •Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
- •Prostate cancer with no plans for therapy of any kind
- •Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- •Subject has a white blood cell count >25 × 10^9/L or absolute blast count of >50 10^9/L. Hydroxyurea and leukapheresis are permitted, if clinically indicated.
- •Patients willing to receive intensive induction chemotherapy
- •Pregnant and breastfeeding females.
研究组 & 干预措施
Azacitidine and Venetoclax
Experimental
Azacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished.
干预措施: Azacitidine (Drug)
Azacitidine and Venetoclax
Experimental
Azacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Response Rate, measured by the European Leukemia Net definition: (CRMRD-+CR+CRi+MLFS)
时间窗: Study start date to study end date, or death, whichever comes first, up to 4 years
The (CRMRD-+CR+CRi+MLFS) shows non-inferiority of venetoclax with azacitidine when compared with historical controls who received induction chemotherapy.
次要结局
- Incidence of Minimal Residual Disease (MRD) Negative Responses(Study start date to study end date, or death, whichever comes first, up to 4 years)
- Remission Duration(Study start date to study end date, or death, whichever comes first, up to 4 years)
- One Year Event Free Survival(Study start date to study end date, or death, whichever comes first, up to 4 years)
- Overall Survival(Study start date to study end date, or death, whichever comes first, up to 4 years)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Study start date to study end date, or death, whichever comes first, up to 4 years)
研究者
研究点 (2)
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