Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML

Phase 3Active Not RecruitingNCT05177731

Chen Suning188 enrolled

Overview

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)

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

188

Conditions

AML, Adult Chemotherapy Effect

Interventions

VenetoclaxDRUG

Orally by mouth

Decitabine for InjectionDRUG

Intravenous infusion

CytarabineDRUG

Intravenous infusion

Idarubicin

Eligibility

Sex: ALLMin age: 18 YearsMax age: 59 Years

Medical Language ↔ Plain English

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.

Locations (1)

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Suzhou, Jiangsu, China

Outcomes

Primary Outcomes

Overall response rate (ORR)

Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State

Time frame: From randomization to 2 cycles of induction before consolidation therapy（100 days）

Secondary Outcomes

Incidence of severe infection (>=grade 3 )

Assessed using CTCAE 5

Time frame: From randomization to 2 cycles of induction before consolidation therapy（100 days）

Duration of myelosuppression

The duration of absolute value of peripheral blood neutrophils \<0.5×10\^9/L and platelet count \<50×10\^9/L during myelosuppression.

Time frame: From randomization to 2 cycles of induction before consolidation therapy（100 days）

Event free survival

Events include progressive disease, relapse, changes in treatment regimens, fatal or intolerable side effects and any death.

Time frame: From the time from randomization to time for up to 2 years

Overall survival

Time frame: From the time from randomization to time for up to 2 years

Rate of Minimal Residual Disease (MRD) negativity

Percentage of participants who converted to MRD \< 10\^-3 before initiation of consolidation therapy.

Time frame: From randomization to 2 cycles of induction before consolidation therapy（100 days）

Data from ClinicalTrials.gov

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