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

NCT05528354 | Unknown Early Phase 1

• 1 other identifier: IIT20220036C-R1
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic Stem Cell Transplantation; TP53

Keywords

hematopoietic stem cell transplantation; TP53; relapse; decitabine

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The time from transplantation to the occurrence of any of the following: 1. Death from any cause 2. Disease recurrence, defined as one of the following: Leukemia blasts reappeared in peripheral blood, or blasts ≥ 5%, naive monocytes ≥ 5% in bone marrow, or extramedullary lesions.

  At Year 1

Secondary Outcomes (6)

• Overall survival (OS)

  At Year 1

• Cumulative relapse rate

  At Year 1

• Non-relapse mortality (NRM)

  At Year 1

• Acute graft-versus-host disease (GVHD)

  At Day 100

• Chronic graft-versus-host disease (GVHD)

  through study completion, an average of 1 year

Study Arms (1)

VEN and DEC based conditioning regimen followed with post-HSCT DEC maintenance therapy

EXPERIMENTAL

Drug: VEN and DEC based conditioning regimen; Drug: DEC

Interventions

VEN and DEC based conditioning regimen DRUG

Patients with age\<50 years and HCT-CI\<3: Haploidentical transplantation: AraC 2g/m2 d-10\~d-9, BU 0.8mg/kg q6h d-8\~-6, CTX 1.8g/m2 d-5\~d-4, Meccnu 250mg/m2 d-3, ATG 1.5mg/kg/d d-5\~-2, VEN 400mg/d d-15\~-9, DEC 20mg/m2 d-15\~-11; HLA-matched transplantation: BU 0.8mg/kg q6h d-7\~-4, CTX 60mg/kg d-3\~d-2, Meccnu 250mg/m2 d-1, VEN d-12\~-8, DEC 20mg/m2 d-12\~-6, and ATG for the unrelated donor type. Patients with age\>50 years or HCT-CI≥3: Flu 30mg/m2 d-10\~-5, BU 0.8mg/kg q6h d-7\~-5, Meccnu 250mg/m2 d-4, ATG 7.5mg/kg divided into d-4\~-1, VEN d-15\~-9, DEC 20mg/m2 d-15\~-11. Note: if Voriconazole or Posaconazole is used to prevent or treat fungal infections, VEN should be 200mg/d for 7 consecutive days.

VEN and DEC based conditioning regimen followed with post-HSCT DEC maintenance therapy

DEC DRUG

In the time window of 60-120 days after transplantation: DEC 5mg/m2/d for 5 consecutive days every 6 to 8 weeks with a total of 4 to 6 courses if there is no severe aGVHD (grade 3 or higher) and the donor chimerism rate of bone marrow blood (STR)\>95%. If the MRD turns positive, DLI can be performed.

VEN and DEC based conditioning regimen followed with post-HSCT DEC maintenance therapy

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Active autoimmune diseases, such as SLE, rheumatoid arthritis, etc.
• 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;
• Other serious medical conditions (e.g., advanced infection) that may limit the patient's participation in the trial;
• 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);
• Pregnant or lactating women;
• Fail to understand, comply with the study protocol or sign the informed consent form.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

The First Hospital of Zhejiang Medical Colleage Zhejiang University

Hangzhou, Zhejiang, 310006, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Yanmin Zhao, PhD

CONTACT

+8615858199217; yanminzhao@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 28, 2022
• First Posted: September 6, 2022
• Study Start: June 2, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 6, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)