AML, Adult, Chemotherapy Effect
Conditions
Keywords
Venetoclax, AML, young, induction therapy
Brief summary
This research is being done to assess the therapeutic efficacy and safety of a promising (venetoclax and decitabine) versus conventional 7+3chemotherapy 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)
Detailed description
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.
Interventions
DRUGVenetoclax
Orally by mouth
Intravenous infusion
DRUGCytarabine
Intravenous infusion
DRUGIdarubicin
Intravenous infusion
DRUGGilteritinib
Orally by mouth
Sponsors
Chen Suning
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
De novo adult AML patients randomly assigned to two induction treatment groups: venetoclax+decitabine group and conventional idarubicin(12mg/m2)+cytarabine group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 59 \> =Age (years) \>= 18; 2. Newly diagnosed as AML patients according to World Health Organization (WHO) 2016 classification; 3. Patients have not received prior therapy for AML (except hydroxyurea and Ara-C\<1.0g/d); 4. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ; 5. 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) 6. Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; 7. 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.
Exclusion criteria
1. Acute promyeloid leukemia； 2. AML with central nervous system (CNS) infiltration； 3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML； 4. HIV infection; 5. Patients with severe heart failure (grade 3-4) ; 6. 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 7. Patients deemed unsuitable for enrolment by the investigator; 8. Patients willing to receive intensive induction chemotherapy 9. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen； 10. Patients reject to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | From randomization to 2 cycles of induction before consolidation therapy（100 days） | Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of severe infection (>=grade 3 ) | From randomization to 2 cycles of induction before consolidation therapy（100 days） | Assessed using CTCAE 5 |
| Duration of myelosuppression | From randomization to 2 cycles of induction before consolidation therapy（100 days） | The duration of absolute value of peripheral blood neutrophils \<0.5×10\^9/L and platelet count \<50×10\^9/L during myelosuppression. |
| Event free survival | From the time from randomization to time for up to 2 years | Events include progressive disease, relapse, changes in treatment regimens, fatal or intolerable side effects and any death. |
| Overall survival | From the time from randomization to time for up to 2 years | Overall survival |
| Rate of Minimal Residual Disease (MRD) negativity | From randomization to 2 cycles of induction before consolidation therapy（100 days） | Percentage of participants who converted to MRD \< 10\^-3 before initiation of consolidation therapy. |
Countries
China
Outcome results
None listed