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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06458244
• Other study ID #: CBF-AML01
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: February 2028

Study information

• Verified date: June 2024
• Source: Ruijin Hospital
• Contact: Yang Shen, MD, PhD
• Phone: 02164370045
• Email: shen_yang[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: February 2028
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 CBFß-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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation

Drug:
• Chemotherapy
Chemotherapy for AML consolidation treatment

Locations

Country	Name	City	State
China	Ruijin Hospital Affiliated to Shanghai Jiaotong University School Of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free-survival	disease-free-survival	from data of AML diagnosis until the data of AML relapse, assessed up to 3 years
Primary	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	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
Secondary	overall survival	overall survival	from data of AML diagnosed until the data of death from any cause, assessed up to 3 years
Secondary	adverse events	adverse events related with the indicated regimen	from enrollment to study completion, a maximum of 3 years