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

Primary Purpose

Relapsed or Refractory Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Selinexor
Homoharringtonine
Daunorubicin
Cytarabine
Granulocyte Colony-Stimulating Factor
Aclacinomycin
Sponsored by
Shanxi Bethune Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

  • Tao WangRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selinexor、HAD or CAG regimens

Arm Description

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.

Outcomes

Primary Outcome Measures

Remission Rate
complete remission rate(CR rate), partial remission rate (PR rate) , no remission rate (NR rate)

Secondary Outcome Measures

Recurrence Rate
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)
A death that is considered to be causally linked to a treatment
Overall Survival (OS)
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)
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
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.

Full Information

First Posted
January 29, 2023
Last Updated
July 16, 2023
Sponsor
Shanxi Bethune Hospital
Collaborators
Antengene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05726110
Brief Title
Selinexor in Combination With HAD or CAG Rregimens in Relapsed or Refractory Acute Myeloid Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 29, 2023 (Actual)
Primary Completion Date
December 10, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanxi Bethune Hospital
Collaborators
Antengene Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Selinexor、HAD or CAG regimens
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
KPT-330
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Homoharringtonine
Other Intervention Name(s)
HHT
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Other Intervention Name(s)
DNR
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Ara-C
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Granulocyte Colony-Stimulating Factor
Other Intervention Name(s)
G-CSF
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Aclacinomycin
Other Intervention Name(s)
ACM
Intervention Description
Given per standard of care
Primary Outcome Measure Information:
Title
Remission Rate
Description
complete remission rate(CR rate), partial remission rate (PR rate) , no remission rate (NR rate)
Time Frame
max 2 years
Secondary Outcome Measure Information:
Title
Recurrence Rate
Description
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).
Time Frame
max 2 years
Title
Treatment-Related Mortality (TRM)
Description
A death that is considered to be causally linked to a treatment
Time Frame
max 2 years
Title
Overall Survival (OS)
Description
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
Time Frame
max 2 years
Title
Event-Free Survival (EFS)
Description
Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
Time Frame
max 2 years
Title
Safety:Incidence and severity of adverse events
Description
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.
Time Frame
max 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tao Wang
Phone
13835175119
Email
wangtao99699@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tao Wang
Organizational Affiliation
Shanxi Bethune Hospital Regulatory Authority
Official's Role
Study Director
Facility Information:
Facility Name
Tao Wang
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tao Wang, doctorial
Phone
13835175119
Email
wangtao99699@163.com

12. IPD Sharing Statement

Learn more about this trial

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

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