Comparing the Efficacy and Safety of Venetoclax Combined With Decitabine Versus Conventional "7+3" Induction Chemotherapy of Acute Myeloid Leukemia in Young Adults
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This research is being done to assess the therapeutic efficacy and safety of a promising (venetoclax and decitabine) versus conventional "7+3"chemotherapy in induction young patients with acute myeloid leukemia.
This study involves the following:
Venetoclax and decitabine (investigational combination) Cytarabine and idarubicin (per standard of care)
详细描述
This is an open-label, multicenter, phase 2 randomized clinical trial to compare the therapeutic efficacy and safety of venetoclax and decitabine to the conventional induction chemotherapy (7+3 regimen) among fit, young adults with newly diagnosed acute myeloid leukemia (AML).
Conventional induction chemotherapy with idarubicin and cytarabine is the standard of induction chemotherapy for acute myeloid leukemia (AML).
The FDA has approved the combination therapy of venetoclax and decitabine for elderly (> 60 year old) patients with newly diagnosed AML not eligible for intensive chemotherapy. Venetoclax is an inhibitor of BCL-2 (B-cell lymphoma 2, a protein that initiates tumor growth, disease progression, and drug resistance), which can lead to cancer cell death. Decitabine, a demethylation agent, has the potential to synergically target leukemia stem cell populations when combined with venetoclax as its homologous drug azacytidine.
Participants will be randomly assigned to one of the different induction groups and followed with either consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation after remission. After completion of study treatment, participants are followed up every 3 to 6 months for up to 2 years.
It is expected that about 188 people will take part in this research study.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 59 > =Age (years) >= 18;
- •Newly diagnosed as AML patients according to World Health Organization (WHO) 2016 classification;
- •Patients have not received prior therapy for AML (except hydroxyurea and Ara-C<1.0g/d);
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
- •Liver function: Total bilirubin ≦3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN(except extramedullary infiltration of leukemia)
- •Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min;
- •Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.
排除标准
- •Acute promyeloid leukemia；
- •AML with central nervous system (CNS) infiltration；
- •Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
- •HIV infection;
- •Patients with severe heart failure (grade 3-4) ;
- •Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Uncontrolled and/or active systemic infection (viral, bacterial or fungal); b) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. c) An active second cancer that requires treatment within 6 months of study entry
- •Patients deemed unsuitable for enrolment by the investigator;
- •Patients willing to receive intensive induction chemotherapy
- •Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen；
- •Patients reject to participate in the study.
研究组 & 干预措施
Investigational ( venetoclax, decitabine)
Randomized participants will receive induction as decitabine on days 1-5 and venetoclax daily on days 1-28.
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%):Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD (Minimal Residual Disease) negative or refuse to allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Venetoclax (Drug)
Investigational ( venetoclax, decitabine)
Randomized participants will receive induction as decitabine on days 1-5 and venetoclax daily on days 1-28.
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%):Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD (Minimal Residual Disease) negative or refuse to allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Decitabine for Injection (Drug)
Investigational ( venetoclax, decitabine)
Randomized participants will receive induction as decitabine on days 1-5 and venetoclax daily on days 1-28.
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%):Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD (Minimal Residual Disease) negative or refuse to allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Gilteritinib (Drug)
Standard of Care (Conventional Induction "7+3")
Randomized participants will receive cytarabine and idarubicin per standard of care as follows:
Induction: cytarabine on days 1-7 and idarubicin (12mg/m2) on days 1-3 .
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%): Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD negative or refuse to allo-HSCT, intermediate-dose cytarabine (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Cytarabine (Drug)
Standard of Care (Conventional Induction "7+3")
Randomized participants will receive cytarabine and idarubicin per standard of care as follows:
Induction: cytarabine on days 1-7 and idarubicin (12mg/m2) on days 1-3 .
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%): Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD negative or refuse to allo-HSCT, intermediate-dose cytarabine (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Idarubicin (Drug)
Standard of Care (Conventional Induction "7+3")
Randomized participants will receive cytarabine and idarubicin per standard of care as follows:
Induction: cytarabine on days 1-7 and idarubicin (12mg/m2) on days 1-3 .
Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%): Re-induction with pre-induction therapy.
Consolidation: If patients with favorable risk and MRD negative or refuse to allo-HSCT, intermediate-dose cytarabine (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.
For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.
干预措施: Gilteritinib (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: From randomization to 2 cycles of induction before consolidation therapy（100 days）
Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State
次要结局
- Overall survival(From the time from randomization to time for up to 2 years)
- Event free survival(From the time from randomization to time for up to 2 years)
- Duration of myelosuppression(From randomization to 2 cycles of induction before consolidation therapy（100 days）)
- Incidence of severe infection (>=grade 3 )(From randomization to 2 cycles of induction before consolidation therapy（100 days）)
- Rate of Minimal Residual Disease (MRD) negativity(From randomization to 2 cycles of induction before consolidation therapy（100 days）)
研究者
Chen Suning
Physician
The First Affiliated Hospital of Soochow University