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Study of Selinexor Combined With Chidamide in Relapsed/Refractory Acute Leukemia (AML) Patients

Primary Purpose

Acute Myeloid Leukemia (Relapsed/Refractory)

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Selinexor
Chidamide
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (Relapsed/Refractory) focused on measuring relapsed/refractory, AML, selinexor and chidamide

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Men and women aged 18 to 75 years old. Diagnosis of relapsed or refractory AML (defined according to the the World Health Organization [WHO] 2016 criteria) of any type except for acute promyelocytic leukemia (APL; AML M3). Eastern Cooperative Oncology Group (ECOG) performance status of 2-3. Patients whose expecting survival time will be more than 3 months. One of the serious heart, lung, liver, kidney disease: Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); Creatinine clearance >= 30 mL/min to < 45 ml/min; Other comorbidities that the physician judges to be incompatible with intensive chemotherapy. Patients who had not received radiotherapy, chemotherapy, targeted therapy within one week before enrollment. Fertile women and men whose partner is of childbearing potential or pregnant should agree to practice complete abstinence or to use a condom during therapy and dose interruptions and for 90 days after the last treatment. Patients who are suitable for intensive chemotherapy but refuse it. Patients who have known and voluntarily signed the informed consent (ICF). Exclusion Criteria: History of any malignancies prior to study entry with exception noted in the protocol. Patients who had previously been treated with selinexor and/or chidamide. Patients with APL/AML M3, or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML. Absolute white blood cell count >=100*10^9/L. Persistent toxicity due to previous chemotherapy or radiotherapy did not recover to 2 grade. Presence of CNS leukemia. Patients who had undergone cardiac angioplasty or stent implantation within 12 months before signing the informed consent form, or had myocardial infarction or instability history of defined angina or other clinically significant cardiac events. Ucontrolled active infection (including bacterial, fungal or viral infections) and bleeding from internal organs. Pregnant and lactating women. Participated in any other clinical trials within 3 months before signing the informed consent form. Patients who are unsuitable for this study judged by clinicians.

Sites / Locations

  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selinexor combined with chidamide

Arm Description

R/R AML who are ineligible for intensive chemotherapy will receive selinexor in combination with chidamide, 28 days per cycle, Selinexor will be used as 40 or 60mg BIW for two weeks, and chidamide will be used as 10mg/d from day 1 to 28. Depending on the level of recovery, patients will either be forced to come off study or have the option to continue the medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.

Outcomes

Primary Outcome Measures

Number of Participants With ORR
Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + morphologic leukemia-free state (MLFS) + partial response (PR).

Secondary Outcome Measures

Duration of Response (DOR)
Defined as time, in months, from initial response (CR+CRi+PR+MLFS) until the date of a disease progression
Event-free survival (EFS)
Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Overall Survival (OS)
Calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Number of Adverse Events (AE)
Adverse events are evaluated with CTCAE V5.0.

Full Information

First Posted
June 24, 2023
Last Updated
July 16, 2023
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05951855
Brief Title
Study of Selinexor Combined With Chidamide in Relapsed/Refractory Acute Leukemia (AML) Patients
Official Title
Selinexor in Combination With Chidamide in Unfit Relapsed/Refractory Acute Leukemia: a Phase 2, Single-Arm, Open-Label, Multi-Center Prospective Study.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

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

5. Study Description

Brief Summary
This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor combined with chidamide in the treatment of unfit R/R AML.
Detailed Description
This protocol corresponds to a multicenter, open-label, single arm, prospective study designed to determine the efficacy and safety of selinexor in combination with chidamide for unfit R/R AML. Selinexor will be given orally at 40 or 60mg on d1,4,8,11; Chidamide will be given orally at 10mg on d1-28; 28 days per cycle. patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive treatment until disease progression or unacceptable toxic effects. After completion of study treatment, participants are followed up every 3 to 6 months for up to 2 years. Study design allows 42 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (Relapsed/Refractory)
Keywords
relapsed/refractory, AML, selinexor and chidamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Selinexor combined with chidamide
Arm Type
Experimental
Arm Description
R/R AML who are ineligible for intensive chemotherapy will receive selinexor in combination with chidamide, 28 days per cycle, Selinexor will be used as 40 or 60mg BIW for two weeks, and chidamide will be used as 10mg/d from day 1 to 28. Depending on the level of recovery, patients will either be forced to come off study or have the option to continue the medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
X
Intervention Description
Selinexor 60mg/day, weight≥70kg (40mg/day, weight<70kg) orally on d1,4,8,11,
Intervention Type
Drug
Intervention Name(s)
Chidamide
Other Intervention Name(s)
C
Intervention Description
Chidamide 10mg/day, orally on day 1 to 28
Primary Outcome Measure Information:
Title
Number of Participants With ORR
Description
Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + morphologic leukemia-free state (MLFS) + partial response (PR).
Time Frame
28 days after study treatment
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
Defined as time, in months, from initial response (CR+CRi+PR+MLFS) until the date of a disease progression
Time Frame
2 years
Title
Event-free survival (EFS)
Description
Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Time Frame
Time from registration to event, max 3 years
Title
Overall Survival (OS)
Description
Calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
Time Frame
Time from registration to event, max 3 years
Title
Number of Adverse Events (AE)
Description
Adverse events are evaluated with CTCAE V5.0.
Time Frame
continuously from first administration of study drug untill 30 days after last study treatment. (approximately up to 1 year)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women aged 18 to 75 years old. Diagnosis of relapsed or refractory AML (defined according to the the World Health Organization [WHO] 2016 criteria) of any type except for acute promyelocytic leukemia (APL; AML M3). Eastern Cooperative Oncology Group (ECOG) performance status of 2-3. Patients whose expecting survival time will be more than 3 months. One of the serious heart, lung, liver, kidney disease: Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); Creatinine clearance >= 30 mL/min to < 45 ml/min; Other comorbidities that the physician judges to be incompatible with intensive chemotherapy. Patients who had not received radiotherapy, chemotherapy, targeted therapy within one week before enrollment. Fertile women and men whose partner is of childbearing potential or pregnant should agree to practice complete abstinence or to use a condom during therapy and dose interruptions and for 90 days after the last treatment. Patients who are suitable for intensive chemotherapy but refuse it. Patients who have known and voluntarily signed the informed consent (ICF). Exclusion Criteria: History of any malignancies prior to study entry with exception noted in the protocol. Patients who had previously been treated with selinexor and/or chidamide. Patients with APL/AML M3, or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML. Absolute white blood cell count >=100*10^9/L. Persistent toxicity due to previous chemotherapy or radiotherapy did not recover to 2 grade. Presence of CNS leukemia. Patients who had undergone cardiac angioplasty or stent implantation within 12 months before signing the informed consent form, or had myocardial infarction or instability history of defined angina or other clinically significant cardiac events. Ucontrolled active infection (including bacterial, fungal or viral infections) and bleeding from internal organs. Pregnant and lactating women. Participated in any other clinical trials within 3 months before signing the informed consent form. Patients who are unsuitable for this study judged by clinicians.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huiying Qiu, Ph.D
Phone
13912792913
Email
qiuhuiying@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Depei Wu, Ph.D
Phone
67781856
Email
drwudepei@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huiying Qiu, Ph.D
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huiying Qiu, Ph.D
Phone
13912792913
Email
qiuhuiying@aliyun.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Selinexor Combined With Chidamide in Relapsed/Refractory Acute Leukemia (AML) Patients

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