Clinical trial NCT05951855: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (Relapsed/Refractory)
Keywords: relapsed/refractory
AML
selinexor and chidamide
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-07-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Men and women aged 18 to 75 years old.
2. 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).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 2-3.
4. Patients whose expecting survival time will be more than 3 months.
5. One of the serious heart, lung, liver, kidney disease:

   1. Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction \<= 50% or chronic stable angina;
   2. Diffusing capacity of the Lung for Carbon Monoxide (DLCO) \<= 65% or Forced Expiratory Volume in 1 second (FEV1) \<= 65%;
   3. Moderate hepatic impairment with total bilirubin \> 1.5 to \<= 3.0 × Upper Limit of Normal (ULN);
   4. Creatinine clearance \>= 30 mL/min to \< 45 ml/min;
6. Other comorbidities that the physician judges to be incompatible with intensive chemotherapy.
7. Patients who had not received radiotherapy, chemotherapy, targeted therapy within one week before enrollment.
8. 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.
9. Patients who are suitable for intensive chemotherapy but refuse it.
10. Patients who have known and voluntarily signed the informed consent (ICF).

Exclusion Criteria:

1. History of any malignancies prior to study entry with exception noted in the protocol.
2. Patients who had previously been treated with selinexor and/or chidamide.
3. Patients with APL/AML M3, or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML.
4. Absolute white blood cell count \>=100\*10\^9/L.
5. Persistent toxicity due to previous chemotherapy or radiotherapy did not recover to 2 grade.
6. Presence of CNS leukemia.
7. 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.
8. Ucontrolled active infection (including bacterial, fungal or viral infections) and bleeding from internal organs.
9. Pregnant and lactating women.
10. Participated in any other clinical trials within 3 months before signing the informed consent form.
11. Patients who are unsuitable for this study judged by clinicians.

Primary outcomes:
measure: Number of Participants With ORR
timeFrame: 28 days after study treatment
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 2 years
measure: Event-free survival (EFS)
timeFrame: Time from registration to event, max 3 years
measure: Overall Survival (OS)
timeFrame: Time from registration to event, max 3 years
measure: Number of Adverse Events (AE)
timeFrame: continuously from first administration of study drug untill 30 days after last study treatment. (approximately up to 1 year)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Huiying Qiu, Ph.D
role: STUDY_CHAIR
References: