Evaluating stem cell transplantation for high-risk acute myeloid leukemia

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

This study is testing if stem cell transplantation after chemotherapy can help people with high-risk acute myeloid leukemia live longer and stay free of the disease.

Quick facts

• Study type: Observational
• Enrollment: 90 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06458244 on ClinicalTrials.gov

What this trial studies

This observational study focuses on patients with newly diagnosed high-relapse-risk core-binding-factor acute myeloid leukemia (CBF-AML). Participants will undergo allogeneic hematopoietic stem cell transplantation after completing one cycle of induction chemotherapy and two cycles of consolidation chemotherapy. The study aims to assess the effectiveness of this treatment regimen by evaluating disease-free survival, overall survival, and non-relapse mortality rates among participants. The study specifically targets individuals with high-risk gene mutations or complex karyotypes that increase the likelihood of disease recurrence.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with confirmed high-risk CBF-AML and specific genetic mutations or MRD positivity.

Not a fit: Patients with low-risk CBF-AML or those with treatment-related acute myeloid leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with high-risk CBF-AML.

How similar studies have performed: Previous studies have shown promising results with allogeneic stem cell transplantation in similar high-risk leukemia populations, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital Affiliated to Shanghai Jiaotong University School Of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Yang Shen, MD, PhD

Conditions Acute Myeloid Leukemia; core binding factor; high-risk; newly diagnosed