Selinexor in Combination With HAD or CAG Rregimens in Relapsed or Refractory Acute Myeloid Leukemia

Sponsor

Shanxi Bethune Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05726110

Collaborator

Antengene Corporation (Industry)

Enrollment

Location

Arm

23.1

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial studies the efficacy and safety of selinexor combined with HAD or CAG regimen in the treatment of relapsed or refractory acute myeloid leukemia

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Acute Myeloid Leukemia	Drug: Selinexor Drug: Homoharringtonine Drug: Daunorubicin Drug: Cytarabine Drug: Granulocyte Colony-Stimulating Factor Drug: Aclacinomycin	Phase 1

Detailed Description

Main Purpose：

To observe the efficacy of selinexor in combination with HAD or CAG regimen for relapsed and refractory acute myeloid leukemia :complete remission rate (CR rate), partial remission rate (PR rate), no remission rate (NR rate), complete remission with incomplete hematologic recovery(CRi rate)

Secondary Purposes：

To observe the recurrence rate of selinexor combined with HAD or CAG regimen for relapsed and refractory acute myeloid leukemia, treatment-related mortality(TRM), Overall Survival (OS), Event-Free Survival (EFS);
Safety indicators: to observe adverse events and deaths during treatment with selinexor in combination with HAD or CAG regimen.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single-arm Open-label Multicenter Clinical Study of Selinexor in Combination With HAD or CAG Rregimens in Relapsed or Refractory Acute Myeloid Leukemia

Actual Study Start Date :

Jan 29, 2023

Anticipated Primary Completion Date :

Dec 10, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Selinexor、HAD or CAG regimens Selinexor (60 mg) is used twice weekly for two weeks (four times, 240 mg total of selinexor) in combination with HAD or CAG regimens for reinduction therapy in patients with relapsed and refractory AML. (Bone marrow image indicates active hyperplasia) HAD regimen: homoharringtonine (HHT) (2mg/ m^2/d)×7days, daunorubicin (DNR, 40mg/ m^2/d)×3 days, cytarabine (Ara-C,100-200mg/ m^2/d)×7 days (no leukocyte drugs should be used throughout the treatment process)； (Bone marrow image indicates hypoproliferation)CAG regimen: Granulocyte Colony-Stimulating Factor (G-CSF, 5ug/kg/d, started 12 hours before chemotherapy×14 days (d1-d14), aclacinomycin (20mg/d)×4 days (d1-4), cytarabine (10 mg/ m^2, subcutaneous injection, 1 time in 12 hours)×14 days (d1-d14). G-CSF was discontinued in the CAG regimen when WBC > 20×10^9/L, but chemotherapy was not stopped.	Drug: Selinexor Given PO Other Names: KPT-330 Drug: Homoharringtonine Given per standard of care Other Names: HHT Drug: Daunorubicin Given per standard of care Other Names: DNR Drug: Cytarabine Given per standard of care Other Names: Ara-C Drug: Granulocyte Colony-Stimulating Factor Given per standard of care Other Names: G-CSF Drug: Aclacinomycin Given per standard of care Other Names: ACM

Arm

Intervention/Treatment

Experimental: Selinexor、HAD or CAG regimens

Selinexor (60 mg) is used twice weekly for two weeks (four times, 240 mg total of selinexor) in combination with HAD or CAG regimens for reinduction therapy in patients with relapsed and refractory AML. (Bone marrow image indicates active hyperplasia) HAD regimen: homoharringtonine (HHT) (2mg/ m^2/d)×7days, daunorubicin (DNR, 40mg/ m^2/d)×3 days, cytarabine (Ara-C,100-200mg/ m^2/d)×7 days (no leukocyte drugs should be used throughout the treatment process)； (Bone marrow image indicates hypoproliferation)CAG regimen: Granulocyte Colony-Stimulating Factor (G-CSF, 5ug/kg/d, started 12 hours before chemotherapy×14 days (d1-d14), aclacinomycin (20mg/d)×4 days (d1-4), cytarabine (10 mg/ m^2, subcutaneous injection, 1 time in 12 hours)×14 days (d1-d14). G-CSF was discontinued in the CAG regimen when WBC > 20×10^9/L, but chemotherapy was not stopped.

Drug: Selinexor

Given PO

Other Names:

KPT-330

Drug: Homoharringtonine

Given per standard of care

Other Names:

HHT

Drug: Daunorubicin

Given per standard of care

Other Names:

DNR

Drug: Cytarabine

Given per standard of care

Other Names:

Ara-C

Drug: Granulocyte Colony-Stimulating Factor

Given per standard of care

Other Names:

G-CSF

Drug: Aclacinomycin

Given per standard of care

Other Names:

ACM

Outcome Measures

Primary Outcome Measures

Remission Rate [max 2 years]
complete remission rate(CR rate), partial remission rate (PR rate) , no remission rate (NR rate)

Secondary Outcome Measures

Recurrence Rate [max 2 years]
After complete remission, (1) naive cells appear in peripheral blood; (2) >5% of bone marrow naive cells; (3) Extramedullary recurrence(refer to the 2014 NCCN guidelines).
Treatment-Related Mortality (TRM) [max 2 years]
A death that is considered to be causally linked to a treatment
Overall Survival (OS) [max 2 years]
Overall survival is a secondary endpoint that will be measured as time from the start of treatment until death from any cause, or the last date the patient was known to be alive
Event-Free Survival (EFS) [max 2 years]
Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
Safety:Incidence and severity of adverse events [max 2 years]
To evaluate the possible adverse events and deaths during treatment with selinexor in combination with HAD or CAG，mainly including liver toxicity, cardiotoxicity, bacterial infection, viral infection, fungal infection.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age:18-60 years old;
Except for patients with AML-M3 with acute myeloid leukemia；
Meet the diagnostic criteria for refractory AML (2011 Chinese guidelines for the diagnosis and treatment of acute myeloid leukemia (relapsed or refractory)):(1) The standard regimen did not achieve complete remission after 2 courses of induction chemotherapy;(2) Relapse within 6 months after the first complete remission; (3) Patients who relapse after 6 months after the first complete remission, and those who fail to induce chemotherapy after the original program; (4) 2 or more recurrences; (5) Extramedullary leukemia persists；
Meet the diagnostic criteria for recurrent AML (refer to the 2014 NCCN guidelines): after complete remission, (1) naive cells appear in peripheral blood; (2) >5% of bone marrow naive cells; (3) Extramedullary recurrence；
The bone marrow image indicates active hyperplasia or hypoproliferation；
Eastern Oncology Collaborative Group Physical Status Assessment (ECOG-PS) with a score of 0-2.

Exclusion Criteria:

Accompanied by cerebral hemorrhage；
Pregnancy；
Have a mental illness or other condition that cannot proceed as planned；
Severe arrhythmia, abnormal ECG (QT>500ms).

Early withdrawal from test criteria：

Participants have the right to withdraw from the study at any time from the trial. Exit

Criteria:

The subject or the subject's legally authorized representative requests to withdraw from the study;
Participant loss to follow-up.

Doctor/Investigator required subjects to terminate the trial early:

Subjects who are unable to carry out follow-up treatment due to adverse events (serious irreversible organ function damage during treatment) who are judged by the investigator to be unsuitable for continuing the research;
The subject does not adhere to the protocol, such as the use of chemotherapy drugs, etc., which affects the effectiveness and safety judgment.

For participants who withdrew early from the study (except subjects who were lost to follow-up), the reason for their early withdrawal should be recorded, and the time of the last study's medication/treatment should be recorded, and the examination items at the time of early withdrawal from the study should be completed at the last visit, if possible.