Twice-per-weekSelinexor, 2 Days Melphalan

Institute of Hematology & Blood Diseases Hospital, China

Status and phase

Not yet enrolling

Phase 3

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Selinexor

Drug: Melphalan

Drug: Fludarabine

Drug: Intravenous Busulfan

Study type

Interventional

Funder types

Other

Identifiers

NCT06613035

IIT2024062

Details and patient eligibility

About

Full description

Twice-per-week Selinexor, 2 days Melphalan plus BU2FLU3 compared with BU3FLU5 for elder high-risk acute myeloid leukemia undergoing allogenic hematopoietic cell transplantation: a multi-center randomized phase 3 trial Primary Objective The primary objective of this study is to compared 1-year RFS between Sel2Mel2BU2FLU3 and BU3FLU5 groups for elder AML in CRc undergoing allo-HCT.

Secondary Objective The secondary objective of this study is to compare leukemia relapse, engraftment, GVHD, OS, TRM, AEs and RRT between Sel2Mel2BU2FLU3 and BU3FLU5 groups

Enrollment

126 estimated patients

Sex

All

Ages

55+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

1. Patients with high-risk acute myeloid leukemia (excluding acute promyelocytic leukemia).
2. Recipients of allogeneic hematopoietic stem cell transplantation (including HLA-matched or mismatched allogeneic transplantation as well as unrelated donor transplantation).
3. Age ≥ 55 years. 4. Disease status prior to allogeneic transplantation must be complete remission (CRc), confirmed by bone marrow analysis within three days prior to randomization.
4. Karnofsky Performance Score (KPS) of at least 60. 6. Informed consent must be signed prior to the commencement of the study procedures. If the patient's signature would be detrimental to their treatment due to their medical condition, the informed consent may be signed by a legal guardian or an immediate family member of the patient.

Note: *High-risk AML: ① Patients classified as high-risk according to the ELN 2022 grading criteria. ② AML patients with persistent MRD positivity prior to transplantation. ③ Patients with refractory or relapsed AML.

Exclusion criteria

1. Previous history of hematopoietic stem cell transplantation. 2. Active cardiac disease, defined as one or more of the following:
2. History of uncontrolled or symptomatic angina.
3. Myocardial infarction within the last 6 months prior to study enrollment.
4. History of arrhythmias requiring medication or with clinically significant symptoms.
5. Uncontrolled or symptomatic congestive heart failure (NYHA class > 2).
6. Ejection fraction below the lower limit of the normal range. 3. Respiratory failure (PaO2 ≤ 60 mmHg). 4. Liver dysfunction (total bilirubin ≥ 3 mg/dL, transaminases > twice the upper limit of normal).
7. Renal dysfunction (creatinine clearance rate < 30 mL/min). 6. Presence of psychiatric disorders or other conditions that prevent cooperation with the study treatment and monitoring requirements.
8. ECOG performance status of ≥ 4. 8. Uncontrolled or active infection. 9. Any condition that impairs the ability to provide informed consent. 10. Any conditions deemed unsuitable for enrollment by the investigator prior to randomization.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

126 participants in 2 patient groups

SMBF group will receive the following Sel2Mel2BU2FLU3 conditioning regimen

Experimental group

Description:

* Selinexor: 60 mg/day from days -9 to -5. * Melphalan: 60 mg/m² on days -8 and -7. * Intravenous Busulfan (Bu): 3.2 mg/kg on days -6 and -5. * Fludarabine (Flu): 30 mg/m² on days -4, -3, and -2.

Treatment:

Drug: Fludarabine

Drug: Intravenous Busulfan

Drug: Melphalan

Drug: Selinexor

Patients in the BF group will receive the BU3FLU5 conditioning regimen

Experimental group

Description:

* Intravenous Busulfan (Bu): 3.2 mg/kg on days -9, -8, and -7. * Fludarabine (Flu): 30 mg/m² on days -6, -5, -4, -3, and -2.

Treatment:

Drug: Fludarabine

Drug: Intravenous Busulfan