Molecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

NCT06972641 | Recruiting Phase 2 DMC

• 1 other identifier: 20250404
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, multicenter, open-label umbrella clinical study planned to enroll 126 subjects with acute myeloid leukemia/myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation. Subjects eligible for enrollment were grouped based on the results of the initial myeloid genomic second-generation sequencing, and were given different regimens of maintenance therapy, with the aim of evaluating the efficacy and safety of the maintenance regimen.

Conditions

AML; MDS

Outcome Measures

Primary Outcomes (1)

• EFS

  Event-free survival

  2 years after transplantation

Secondary Outcomes (1)

• OS

  2 years after transplantation

Study Arms (4)

ARM3: KIT mutation

EXPERIMENTAL

Initial bone marrow gene II sequencing showed KIT mutations (loci: D816, N822, exon 8, VAF ≥2%, excluding germline mutations); no TP53 mutations, AML/MR, FLT3-ITD;

Drug: Avastinib

ARM2: FLT3-ITD mutation

EXPERIMENTAL

Initial bone marrow gene II sequencing showed FLT3-ITD mutation with or without NPM1 mutation, no TP53 mutation, and no AML/MR.

Drug: Sorafenib (BAY-43-9006)，giritinib

ARM1 TP53 mutation and/or AML-MR

EXPERIMENTAL

TP53 mutation (VAF ≥ 2%, excluding germline mutations), and/or AML-MR (SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2) by second-generation sequencing of the initial bone marrow gene.

Drug: Decitabine

ARM4: Other mutations/fusions

EXPERIMENTAL

MDS in the intermediate/high/very high risk group as assessed by IPSS-M or AML in the intermediate/high risk group as assessed by ELN2022 without ARM1, 2, or 3 related mutations/fusions;

Drug: Venetoclax;Selenisol

Interventions

Decitabine DRUG

Decitabine 3.5 mg/m2 1-5d for 28 days for 6 cycles of dosing

ARM1 TP53 mutation and/or AML-MR

Sorafenib (BAY-43-9006)，giritinib DRUG

Sorafenib 0.2g 2/day or giritinib 40mg 2/day orally for 2 years

ARM2: FLT3-ITD mutation

Avastinib DRUG

100 mg 1/day

ARM3: KIT mutation

Venetoclax;Selenisol DRUG

Vinaclat: 50-100mg 1/day orally, d1-14 1/day per month (adjust drug dosage based on blood levels), 28-day cycle; Selenisol: 20mg qw orally (weeks 1 and 2), 28-day cycle If the above treatment is not tolerated, adjust the regimen to decitabine 3.5 mg/m2 1-5 d; 28 days as a cycle of 6 cycles of medication; Vinaclat: 50-100 mg 1/day orally, d1-14 1/day per month orally (adjust the dose of the drug according to the blood concentration), 28 days as a cycle of medication

ARM4: Other mutations/fusions

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Age 14-75 years and gender; (2) Initial diagnosis, pre-transplant myelogenetic second-generation sequencing data refinement; 3)ARM1: TP53 mutation (VAF ≥ 2%, excluding germline mutations), and/or AML-MR (SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2) by second-generation sequencing of the initial bone marrow gene; ARM2 Initial bone marrow gene II sequencing showed FLT3-ITD mutation with or without NPM1 mutation, no TP53 mutation, and no AML/MR. ARM3 Initial bone marrow gene II sequencing showed KIT mutations (loci: D816, N822, exon 8, VAF ≥2%, excluding germline mutations); no TP53 mutations, AML/MR, FLT3-ITD; ARM4 MDS in the intermediate/high/very high risk group as assessed by IPSS-M or AML in the intermediate/high risk group as assessed by ELN2022 without ARM1, 2, or 3 related mutations/fusions; 4) Subjects receive their first allogeneic hematopoietic stem cell transplantation within 30-60 days and STR-PCR shows complete donor chimerism; 5) Evaluation of the primary disease prior to maintenance therapy as complete remission and negative bone marrow flow MRD; 6) No active infection and no acute graft-versus-host disease requiring systemic treatment 7) Have appropriate organ function and laboratory results within 7 days prior to the start of treatment need to meet the following criteria:
• Aspartate aminotransferase (AST) ≤ 3 times ULN (upper limit of normal, ULN);
• Alanine aminotransferase (ALT) ≤ 3x ULN;
• Total serum bilirubin ≤ 1.5 times the upper limit of normal ULN unless the patient has documented Gilbert's syndrome; patients with Gilbert's syndrome with bilirubin ≤ 3.0 times the upper limit of normal and direct bilirubin ≤ 1.5 times the upper limit of normal may be included;
• Hemoglobin ≥ 70 g/L (had not received a red blood cell transfusion within 1 week prior to administration); Absolute neutrophil count (ANC) ≥ 0.8 x 10\^9/L (had not received long-acting colony-stimulating factor (LACSF) within 1 week prior to administration and short-acting colony-stimulating factor (SACSF) within 3 days prior to administration); and Platelet count ≥ 20 x 10\^9/L (1 week prior to administration) have not received a platelet transfusion);
• Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min;
• Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN, Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN;
• Left ventricular ejection fraction (LVEF) ≥45%; 8) Women of childbearing potential must have a negative serum pregnancy study within 7 days prior to the first dose. Female subjects of childbearing potential and male subjects whose partner is a woman of childbearing potential must agree to use a highly effective method of contraception from the time of signing the informed consent form until 180 days after the last dose of study drug is given (9) Voluntarily signing the informed consent, understanding and complying with the requirements of the study, good compliance, and cooperating with the follow-up visits.

You may not qualify if:

• Patients were not enrolled if they met any of the following criteria:
• Bone marrow or peripheral blood MRD changes from negative to positive;
• Presence of acute or chronic GVHD, active infection requiring systemic immunosuppressive therapy prior to maintenance therapy;
• Have clinically significant active cardiovascular disease such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional class, or a history of myocardial infarction within the 6 months prior to screening;
• Other serious medical conditions that may limit the patient's participation in this trial (e.g., uncontrolled diabetes, active autoimmune disease, etc.);
• Known human immunodeficiency virus (HIV) infection, or chronic infection with hepatitis B virus (HBsAg-positive) or hepatitis C virus (anti-HCV-positive) that is uncontrolled by drugs;
• Patients with neurological or psychiatric disorders;
• Those who are unable to understand or comply with the study protocol or are unable to sign the informed consent form;
• The researcher does not consider it appropriate to participate in this study.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Interventions

Decitabine; Sorafenib

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Central Study Contacts

Xiaoxia Hu

CONTACT

+862164370045; hu_xiaoxia@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: May 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)