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

Chemotherapy Effect Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05177731
• Other study ID #: SZ-AML02
• Status: Recruiting
• Phase: Phase 3
• Start date: March 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Suning Chen
• Phone: +86-13814881746
• Email: chensuning[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

This is an open-label, multicenter, phase Ⅲ randomized clinical trial to compare the therapeutic efficacy and safety of conventional induction chemotherapy (7+3 regimen) to the combination of venetoclax and decitabine 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 consolidated 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 188
• Est. completion date: December 31, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

1. Male or female, 59 > =Age (years) >= 18;

2. Newly diagnosed as AML patients according to World Health Organization (WHO) 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.

Related Conditions & MeSH terms

• AML, Adult
• Chemotherapy Effect

Intervention

Drug:
• Venetoclax
Orally by mouth
• Decitabine for Injection
Intravenous infusion
• Cytarabine
Intravenous infusion
• Idarubicin
Intravenous infusion
• Gilteritinib
Orally by mouth

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Chen Suning

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of severe infection (>=grade 3 )	Assessed using CTCAE 5	From randomization to 2 cycles of induction before consolidation therapy(100 days)
Secondary	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.	From randomization to 2 cycles of induction before consolidation therapy(100 days)
Secondary	Event free survival	Events include progressive disease, relapse, changes in treatment regimens, fatal or intolerable side effects and any death.	From the time from randomization to time for up to 2 years
Secondary	Overall survival	Overall survival	From the time from randomization to time for up to 2 years
Secondary	Rate of Minimal Residual Disease (MRD) negativity	Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy.	From randomization to 2 cycles of induction before consolidation therapy(100 days)