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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Decitabine for Injection; Drug: VENCLYXTO

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weiyan Zheng, MD; Phone Number: 86-13857187088; Email: zhengwy2015@163.com
• Study Contact Backup: Name: Xuepin Luo, MD; Phone Number: 86-15167157190; Email: luoxp1603@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Weiyan Zheng, MD; Phone Number: 86-13857187088; Email: zhengwy2015@163.com
      • Principal Investigator: Weiyan Zheng, MD
      • Sub-Investigator: Xuepin Luo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate(CR+CRi)	Assessment of CR(CR=CR+CRi) at Week 8	at Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD	Assessment of minimal residual disease (MRD) at Week 8	at Week 8
EFS	Evaluation of Event-free survival (EFS)	up to 2 years after induction therpy
OS	Evaluation of overall survival (OS)	up to 2 years after induction therpy

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Weiyan Zheng, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2023
• Primary Completion (Estimated): October 19, 2025
• Study Completion (Estimated): October 19, 2026

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 2, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: IIT202300032C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No