Prolonged Ultra Low-dose Decitabine Plus Venetoclax for Primary Diagnosed Elderly AMLK/MDS

Acute Myeloid Leukemia Clinical Trial

Official title:

A Multi-center Prospective Single Arm Clinical Study of Prolonged Ultra Low-dose Decitabine Combined With Venetoclax (Bcl-2 Inhibitor) as First Line Treatment for Elderly Acute Myeloid Leukemia and High-risk Myelodysplastic Syndromes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06046313
• Other study ID #: IIT202300032C
• Status: Recruiting
• Phase: Phase 2
• Start date: October 19, 2023
• Est. completion date: October 19, 2026

Study information

• Verified date: April 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Weiyan Zheng, MD
• Phone: 86-13857187088
• Email: zhengwy2015[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To explore the efficacy and safety of prolonged low-dose decitabine (10 days of 6mg/m2) plus venetoclax (3 weeks/cycle) regimen in primary diagnosed elderly or frail AML/ high-risk MDS.

Description:

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematological malignancies. Some patients are over 65 years old, have poor response to traditional chemotherapy, and rarely have the opportunity to receive allogeneic hematopoietic stem cell transplantation, resulting in poor prognosis and short survival. In recent years, with the advent of molecular targeted drugs Bcl-2 inhibitors, the treatment of elderly AML/ high-risk MDS has achieved breakthrough progress. In particular, the combination of demethylated drugs (decitabine/azacidacidin) and Bcl-2 inhibitors of chemotherapy-free regimen has been recommended by NCCN as the first-line treatment for elderly and frail patients. However, how to achieve the optimal combination of decitabine and Bcl-2 inhibitors is an urgent problem to be solved. Our previous pilot trial showed that prolonged low-dose decitabine combined with venetoclax (Bcl-2 inhibitor) resulted in higher complete remission rate, longer disease-free survival, and lower treatment-related risks. The purpose of this study was to expand the multi-center sample to explore the efficacy and safety of prolonged low-dose decitabine plus venetoclax regimen in primary diagnosed elderly or frail AML/ high-risk MDS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 19, 2026
• Est. primary completion date: October 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Patients must be diagnosed with acute myeloid leukemia (non-acute promyelocytic leukemia)/high-risk myelodysplastic syndrome before admission. Diagnostic criteria refer to 2016 WHO classification.

2. Age 60 or older.

3. The scores of physical fitness in the Eastern Tumor Cooperative group (ECOG) ranged from 0 to 3(see Appendix 1).

4. Creatinine clearance =30 mL/min(as assessed by the Cockcrod-Gault formula [Cockcroft et al 1976] [13] or the estimated glomerular filtration rate [eGFR] from the Kidney Drink adjustment formula .

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)=3× upper limit of normal range (ULN), total bilirubin =2×ULN.

6. Echocardiography (ECHO) showed left ventricular ejection fraction (LVEF)=50% (AHA 2016).

7. Life expectancy >8 weeks.

8. Sign the informed consent voluntarily, and understand and comply with the requirements of the study.

Exclusion Criteria:

1. Age <60 years old.

2. Treated patients who had received various chemotherapy regiments.

3. Present clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional scale (see Appendix 2), or history of myocardial infarction in the 6 months prior to screening.

4. Other serious diseases that may limit participation in the trial (e.g. advanced infections, uncontrolled diabetes).

5. Those who cannot understand and follow the research plan or sign the informed consent.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Decitabine for Injection
6mg/m2, ivgtt qd d1-10
• VENCLYXTO
100mg p.o.d1, 200mg p.o.d2, 400mg p.o.d3-21,adjust by blood concentration

Locations

Country	Name	City	State
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate(CR+CRi)	Assessment of CR(CR=CR+CRi) at Week 8	at Week 8
Secondary	MRD	Assessment of minimal residual disease (MRD) at Week 8	at Week 8
Secondary	EFS	Evaluation of Event-free survival (EFS)	up to 2 years after induction therpy
Secondary	OS	Evaluation of overall survival (OS)	up to 2 years after induction therpy