The Efficacy of Allo-HSCT in ND HR-CBF-AML

The Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed High-relapse-risk Core-binding-factor Acute Myeloid Leukemia

For newly diagnosed high-relapse-risk core-binding-factor acute myeloid leukemia participants, the investigators aim to perform allogeneic hematopoietic stem cell transplantation after participants finished one cycle of induction and two cycles of consolidation. To access whether the therapeutic regimen is effective for high-relapse-risk core-binding-factor acute myeloid leukemia, the disease-free-survival (DFS), overall survival (OS), non-relapse-mortality of participants is evaluated.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Chemotherapy

Detailed Description

High-relapse-risk definition:

Participants with high-risk gene mutations or complex karyotypes for disease recurrence, or flow cytometry/gene MRD positivity after two chemotherapy treatments; High-risk gene mutations include: TP53, RTK/RAS signaling (FLT3, NRAS, KRAS, KIT, JAK2, CSF3R), chromatin modification (ASXL1, ASXL2, KMD6A, EZH2, SETD2) or mutations listed as intermediate-risk or high-risk in the 2022NCCN guidelines; The positive threshold for flow cytometry MRD was 0.0001%; The MRD threshold of molecular biology is the lowest value of the detection protocol of the center.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Yang Shen, MD, PhD; Phone Number: 02164370045; Email: shen_yang@126.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Recruiting
      • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
      • Contact: Jian Li, PhD; Phone Number: 021-64370045; Email: lj12116@rjh.com.cn
      • Principal Investigator: Yang Shen, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Newly Diagnosed High-relapse-risk Core-binding-factor Acute Myeloid Leukemia in Ruijin Hospital

Description

Inclusion Criteria:

1. Participants with confirmed CBF-AML. Diagnostic criteria include the presence of t(8; 21)(q22; q22)/RUNX1-RUNX1T1 fusion gene detected at the molecular level; or chromosome presence of inv(16)(p13.1q22)/t(16; 16)(p13.1; q22) /Detection of CBFβ-MYH11 fusion gene at the molecular level;
2. Participants with high-risk gene mutations or complex karyotypes for disease recurrence, or flow cytometry/gene MRD positivity after two chemotherapy treatments; High-risk gene mutations include: TP53, RTK/RAS signaling (FLT3, NRAS, KRAS, KIT, JAK2, CSF3R), chromatin modification (ASXL1, ASXL2, KMD6A, EZH2, SETD2) or mutations listed as intermediate-risk or high-risk in the 2022NCCN guidelines; The positive threshold for flow cytometry MRD was 0.0001%; The MRD threshold of molecular biology is the lowest value of the detection protocol of the center.
3. Medical history and diagnosis of MICM, exclusion of MDS, transformation and treatment-related AML;
4. Age 18-65 years old (18 years old ≤Age< 65 years old);
5. Liver and kidney function: blood bilirubin ≤ 35 μmol/L, AST/ALT below 2 times the upper limit of normal, serum creatinine ≤ 150 μmol/L;
6. Normal cardiac function (EF≥50%, New York Cardiac Function Classification NYHA I/II);
7. Physical condition score 0-2 (ECOG score);
8. For participants with peripheral blood leukocytes < 50*109/L at the initial onset, no chemotherapy has been given except for hydroxyurea before the start of induction therapy;
9. For participants with peripheral blood leukocytes ≥ 50*109/L at the initial onset, cytarabine and hydroxyurea are allowed to be treated before the start of induction therapy;
10. Non-pregnant and lactating women;
11. For all women of childbearing age, a pregnancy test must be performed to measure hCG to rule out pregnancy;
12. Obtain informed consent signed by the patient or family member.

Exclusion Criteria:

1. MDS-converted AML, treatment-related AML; mixed cell leukemia; AML with central nervous system infiltrates and extramedullary lesions at the time of onset;
2. Relapse AML;
3. Allergies or contraindications to any of the drugs involved in the protocol;
4. Liver and kidney function are obviously abnormal, exceeding the enrollment criteria;
5. Cardiac disease: including echocardiogram EF <50%, cardiac insufficiency (New York cardiac function classification NYHA: III/IV), pericardial effusion (CTCAE score >2) within six months after acute myocardial infarction, ECG QTc >470ms;
6. Lung diseases: pulmonary edema, pleural effusion (CTCAE score >2);
7. Suffering from malignant tumors of other organs at the same time;
8. Active patients with HAV, HBV, HCV and tuberculosis, HIV-positive patients;
9. Concomitant other hematologic diseases (including coagulation abnormalities unrelated to leukemia);
10. Inability to understand or follow the study protocol;
11. Those who participate in other clinical studies at the same time; Presence of any other condition that would preclude the conduct of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HSCT-group; The participants receive HSCT after two-cycle of consolidation treatment.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Allogeneic Hematopoietic Stem Cell Transplantation
Chemo-group; The participants receive chemotherapy after two-cycle of consolidation treatment.	Drug: Chemotherapy; Chemotherapy for AML consolidation treatment; Other Names: High-dose cytarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free-survival	disease-free-survival	from data of AML diagnosis until the data of AML relapse, assessed up to 3 years
The relation of CBF-AML genetics subgroup with MRD negativity rate after chemotherapy and DFS after transplantation	The relation of CBF-AML genetics subgroup with MRD negativity rate after chemotherapy and DFS after transplantation	from data of AML diagnosis until the data of CR-achieved status, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of non-relapse-mortality	the ratio of non-relapse-mortality cases and all the mortality cases	the data of death from any cause, assessed up to 3 years
overall survival	overall survival	from data of AML diagnosed until the data of death from any cause, assessed up to 3 years
adverse events	adverse events related with the indicated regimen	from enrollment to study completion, a maximum of 3 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Study Director: Yang Shen, MD, PhD, Ruijin Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2024
• Primary Completion (Estimated): September 20, 2026
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: core binding factor; high-risk; newly diagnosed
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Arabinonucleosides; Cytarabine; Drug Therapy
• Other Study ID Numbers: CBF-AML01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes