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

NCT05177731 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: SZ-AML02
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

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)

Conditions

AML, Adult; Chemotherapy Effect

Keywords

Venetoclax, AML, young, induction therapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

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

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

Secondary Outcomes (5)

• Incidence of severe infection (>=grade 3 )

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

• Duration of myelosuppression

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

• Event free survival

  From the time from randomization to time for up to 2 years

• Overall survival

  From the time from randomization to time for up to 2 years

• Rate of Minimal Residual Disease (MRD) negativity

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

Study Arms (2)

Investigational ( venetoclax, decitabine)

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Decitabine for Injection; Drug: Gilteritinib

Standard of Care (Conventional Induction "7+3")

EXPERIMENTAL

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.

Drug: Cytarabine; Drug: Idarubicin; Drug: Gilteritinib

Interventions

Venetoclax DRUG

Orally by mouth

Also known as: Venclexta

Investigational ( venetoclax, decitabine)

Decitabine for Injection DRUG

Intravenous infusion

Investigational ( venetoclax, decitabine)

Cytarabine DRUG

Intravenous infusion

Also known as: Ara-C

Standard of Care (Conventional Induction "7+3")

Idarubicin DRUG

Intravenous infusion

Also known as: IDA

Standard of Care (Conventional Induction "7+3")

Gilteritinib DRUG

Orally by mouth

Also known as: XOSPATA

Investigational ( venetoclax, decitabine); Standard of Care (Conventional Induction "7+3")

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chen Suning: lead

Study Sites (1)

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

Suzhou, Jiangsu, 215000, China

Location

Related Publications (2)

• Lu J, Xue SL, Wang Y, He XF, Hu XH, Miao M, Zhang Y, Tang ZX, Xie JD, Yang XF, Xu MZ, Shen YY, Du F, Wu Q, Xue MX, Wang Y, Deng AL, Dou XQ, Xu Y, Dai HP, Wu DP, Chen SN. Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML. Blood. 2025 May 29;145(22):2645-2655. doi: 10.1182/blood.2024027217.

  PMID: 40009498 DERIVED

• Waclawiczek A, Leppa AM, Renders S, Stumpf K, Reyneri C, Betz B, Janssen M, Shahswar R, Donato E, Karpova D, Thiel V, Unglaub JM, Grabowski S, Gryzik S, Vierbaum L, Schlenk RF, Rollig C, Hundemer M, Pabst C, Heuser M, Raffel S, Muller-Tidow C, Sauer T, Trumpp A. Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax. Cancer Discov. 2023 Jun 2;13(6):1408-1427. doi: 10.1158/2159-8290.CD-22-0939.

  PMID: 36892565 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Decitabine; Injections; Cytarabine; Idarubicin; gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Arabinonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Model Details: De novo adult AML patients randomly assigned to two induction treatment groups: venetoclax+decitabine group and conventional idarubicin(12mg/m2)+cytarabine group.

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 5, 2022
• Study Start: March 1, 2022
• Primary Completion: February 28, 2024
• Study Completion: December 31, 2024
• Last Updated: October 3, 2024

Record last verified: 2024-10

Locations

CN (1)