Clinical trial NCT05177731: Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML
Official title: Comparing the Efficacy and Safety of Venetoclax Combined With Decitabine Versus Conventional "7+3" Induction Chemotherapy of Acute Myeloid Leukemia in Young Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: AML, Adult
Chemotherapy Effect
Keywords: Venetoclax, AML, young, induction therapy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2022-01-05
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief summary: 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)

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: From randomization to 2 cycles of induction before consolidation therapy（100 days）
Secondary outcomes:
measure: Incidence of severe infection (>=grade 3 )
timeFrame: From randomization to 2 cycles of induction before consolidation therapy（100 days）
measure: Duration of myelosuppression
timeFrame: From randomization to 2 cycles of induction before consolidation therapy（100 days）
measure: Event free survival
timeFrame: From the time from randomization to time for up to 2 years
measure: Overall survival
timeFrame: From the time from randomization to time for up to 2 years
measure: Rate of Minimal Residual Disease (MRD) negativity
timeFrame: From randomization to 2 cycles of induction before consolidation therapy（100 days）
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
state: Jiangsu
Study officials:
References: