Treatment for TP53 mutant AML/MDS using Venetoclax and Decitabine

Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients

This study is testing a new treatment using Venetoclax and Decitabine to see if it can help people with TP53 mutant acute myeloid leukemia or myelodysplastic syndromes feel better after a stem cell transplant.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 12 Years to 70 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05528354 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of a conditioning regimen using Venetoclax and Decitabine, followed by Decitabine maintenance therapy in patients with TP53 mutant acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Given the poor prognosis associated with TP53 mutations, the study aims to improve outcomes post-hematopoietic stem cell transplantation (HSCT) by targeting malignant clones. The approach is based on the synergistic effects of Venetoclax and Decitabine, which have shown promise in previous treatments. This multicenter, single-arm clinical study will assess the efficacy and safety of this novel treatment protocol.

Who should consider this trial

Good fit: Ideal candidates include patients aged 12 to 70 with a confirmed diagnosis of AML or MDS and a TP53 mutation.

Not a fit: Patients with active autoimmune diseases or significant cardiovascular conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and reduce relapse in patients with TP53 mutant AML/MDS.

How similar studies have performed: While the combination of Venetoclax and Decitabine has shown promise in other studies, this specific approach for TP53 mutant AML/MDS is novel and untested.

Eligibility criteria

Inclusion Criteria:

1. AML or MDS diagnosed according to 2016 WHO criteria with TP53 mutation before enrollment;
2. Aged from 12 to 70 years;
3. The Eastern Cooperative Oncology Group (ECOG) performance score of 0-2;
4. Creatinine clearance rate ≥ 60 mL/min (according to Cockcroft-Gault formula);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 3× upper limit of normal range (ULN), total bilirubin ≤ 2×ULN;
6. Left ventricular ejection fraction (LVEF) assessed by echocardiography (ECHO) ≥ 45%;
7. Life expectancy \> 8 weeks;
8. Sign the informed consent voluntarily, understand and comply with all trial requirements.

Exclusion Criteria:

1. Active autoimmune diseases, such as SLE, rheumatoid arthritis, etc.
2. Current active cardiovascular disease with clinically significance, such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease determined by the New York Heart Association (NYHA) functional classification, or a history of myocardial infarction within the 6 months prior to screening;
3. Other serious medical conditions (e.g., advanced infection) that may limit the patient's participation in the trial;
4. Known human immunodeficiency virus (HIV) infection, or drug-uncontrolled chronic infection of hepatitis B virus (HBV-DNA \> 1000IU/ml) or hepatitis C virus (anti-HCV positive);
5. Pregnant or lactating women;
6. Fail to understand, comply with the study protocol or sign the informed consent form.

Where this trial is running

Hangzhou, Zhejiang

• The First Hospital of Zhejiang Medical Colleage Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yanmin Zhao, PhD

Conditions Hematopoietic Stem Cell Transplantation; TP53; hematopoietic stem cell transplantation; relapse; decitabine