Clinical trial NCT05528354: Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients
Official title: Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hematopoietic Stem Cell Transplantation
TP53
Keywords: hematopoietic stem cell transplantation
TP53
relapse
decitabine
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-09-06
Enrollment: 58
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the effectiveness and safety of Venetoclax and Decitabin based conditioning regimen followed with post-HSCT Decitabin maintenance therapy in TP53 mutant AML/MDS Patients.

Detailed description: In acute myeloid leukemia and myelodysplastic syndromes, TP53 gene mutation is a poor prognostic factor and a strong indication for hematopoietic stem cell transplantation. However, because of the high relapse rate of myeloid tumors with TP53 mutation, new comprehensive treatment is urgently needed to improve the efficacy of transplantation. Decitabin(DEC) has shown certain efficacy in primary patients with TP53 mutation, and Venetoclax (VEN) and DEC have synergistic effect. Based on this, we hypothesized that DEC and VEN should be added to the conditioning regimen in TP53 mutant AML/MDS patients in order to eliminate malignant clones with P53 mutation as much as possible, and intermittent DEC maintenance therapy should be used to prevent relapse after post-HSCT hematopoietic reconstruction. We intend to conduct a multicenter, single-arm clinical study to evaluate the efficacy and safety of this protocol.

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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: At Year 1
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: At Year 1
measure: Cumulative relapse rate
timeFrame: At Year 1
measure: Non-relapse mortality (NRM)
timeFrame: At Year 1
measure: Acute graft-versus-host disease (GVHD)
timeFrame: At Day 100
measure: Chronic graft-versus-host disease (GVHD)
timeFrame: through study completion, an average of 1 year
measure: Adverse effects
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Medical Colleage Zhejiang University
state: Zhejiang
Study officials:
References: