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

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06046313

Collaborator

(none)

120

Enrollment

Location

Arm

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes	Drug: Decitabine for Injection Drug: VENCLYXTO	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 27, 2023

Anticipated Primary Completion Date :

Sep 27, 2025

Anticipated Study Completion Date :

Sep 27, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment group Acute Myeloid Leukemia Myelodysplastic Syndrome	Drug: Decitabine for Injection 6mg/m2, ivgtt qd d1-10 Other Names: Dacogen 5-Aza-29-deoxycytidine Drug: VENCLYXTO 100mg p.o.d1, 200mg p.o.d2, 400mg p.o.d3-21,adjust by blood concentration Other Names: VENLEXTA

Arm

Intervention/Treatment

Experimental: treatment group

Acute Myeloid Leukemia Myelodysplastic Syndrome

Drug: Decitabine for Injection

6mg/m2, ivgtt qd d1-10

Other Names:

Dacogen

5-Aza-29-deoxycytidine

Drug: VENCLYXTO

100mg p.o.d1, 200mg p.o.d2, 400mg p.o.d3-21,adjust by blood concentration

Other Names:

VENLEXTA

Outcome Measures

Primary Outcome Measures

Complete response rate(CR+CRi) [at Week 8]
Assessment of CR(CR=CR+CRi) at Week 8

Secondary Outcome Measures

MRD [at Week 8]
Assessment of minimal residual disease (MRD) at Week 8
EFS [up to 2 years after induction therpy]
Evaluation of Event-free survival (EFS)
OS [up to 2 years after induction therpy]
Evaluation of overall survival (OS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Age 60 or older.
The scores of physical fitness in the Eastern Tumor Cooperative group (ECOG) ranged from 0 to 3(see Appendix 1).
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 .
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤3× upper limit of normal range (ULN), total bilirubin ≤2×ULN.
Echocardiography (ECHO) showed left ventricular ejection fraction (LVEF)≥50% (AHA 2016).
Life expectancy >8 weeks.
Sign the informed consent voluntarily, and understand and comply with the requirements of the study.

Exclusion Criteria:

Age <60 years old.
Treated patients who had received various chemotherapy regiments.
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.
Other serious diseases that may limit participation in the trial (e.g. advanced infections, uncontrolled diabetes).
Those who cannot understand and follow the research plan or sign the informed consent.