Clinical trial NCT05805072: Selinexor and HAAG With/Without HMA in Relapsed/Refractory Acute Leukemia (AML) Patients
Official title: An Open Label, Single Arm, Single-Center Exploratory Study to Evaluate the Efficacy and Safety of Selinexor and HAAG +/- HMA in Relapsed/Refractory Acute Leukemia (AML) Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Relapsed/Refractory AML
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-04-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of selinexor and HAAG +/- HMA in relapsed/refractory acute leukemia (AML) patients.

Detailed description: This protocol corresponds to a single-center, open-label, single-arm, exploratory study designed to determine the efficacy and safety of the combination of selinexor with HAAG +/- HMA in patients with relapsed or refractory AML. The patients who respond to this combination treatment will undergo allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment according to patient's wishes.

Each cycle of treatment will compromise 2 weeks of selinexor treatment, and at least two weeks off treatment. The new cycle will not start if there is an ongoing grade 3 or higher non-hematologic toxicity or persistent grade 3 neutropenia in patients achieving CR.

Study design allows 20 patients. Treatment will consist of selinexor 60 mg/day orally on d1,4,8,11, HHT 1 mg/day intravenously on days 3 to 9, cytarabine 10 mg/m2 q12h, intravenously on days 3 to 9, aclacinomycin 10 mg/day intravenously on days 3 to 6, G-CSF 50-600 mcg/m2/day intravenously from days 2 to start, this dosage will be adjusted according to the hemogram, DAC 20 mg/m2/day intravenously on days 1 to 5. Whether to add hypomethylating agents was decided by the investigator according to the patient's disease degree and tolerance status. If patients had previously been exposed to decitabine, azacitidine will added this regimen, AZA 20 mg/m2/day subcutaneously on days 1 to 7.

Eligibility criteria: Inclusion Criteria:

1. Men and women aged ≥18 years.
2. Diagnosis of AML (defined according to the 5th of the World Health Organization \[WHO\] 2022 criteria) of any type except for acute promyelocytic leukemia (APL; AML M3)and the following conditions were met: Relapsing or refractory AML
3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
4. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use two reliable methods of contraception for six months after their last dose of medication.
5. Patients whose expecting survival time will be more than 3 months.
6. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

1. AML transformed from chronic myeloid leukemia.
2. Patients with APL/AML M3.
3. Presence of CNS leukemia.
4. Uncontrolled infection or other serious disease.
5. Unstable cardiovascular function: Cardiac ejection fraction (EF)\<0.5, or congestive heart failure (CHF) of NYHA Class ≥ 2.
6. Unstable Liver and kidney function:TBLL≥2.0 mg/dl, AST≥3×ULN, Ccr≥50 ml/min, SpO2\<92%.
7. Known human immunodeficiency virus (HIV) infection.
8. Active hepatitis B or hepatitis C infection.
9. Pregnant and lactating women. Patients with other commodities that the investigators considered not suitable for the enrollment.

Primary outcomes:
measure: Number of Participants With CR/CRi
timeFrame: End of cycle 1 and 2 (each cycle is 28 days)
Secondary outcomes:
measure: Number of Participants With ORR
timeFrame: End of cycle 1 and 2 (each cycle is 28 days)
measure: Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
timeFrame: 1-2 induction cycles (4 - 8 weeks)
measure: Progression-Free Survival
timeFrame: Time from registration to event, max 2 years
measure: Overall Survival
timeFrame: Time from registration to event, max 2 years
measure: Number of adverse events
timeFrame: End of cycle 1 and 2 (each cycle is 28 days)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: