Clinical trial NCT04827069: A Clinical Trial to Evaluate Clifutinib in Patients with Relapsed or Refractory Acute Myeloid Leukemia(AML)
Official title: A Phase I, Multi-center, Open,Single Arm, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Clifutinib Besylate(HEC73543) in Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Arm 1:10 mg Arm 2:20 mg Arm 3:40 mg Arm 4:55 mg Arm 5:70 mg Arm 6: 100 mg
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of Clifutinib Besylate in Relapsed/refractory AML patients with FLT3-ITD mutation.

Detailed description: It is a multi-center , open-label, single arm study conducted in 2 parts. Dose-escalation part: Subjects will receive oral Clifutinib Besylate once on C0D1.After 3 days,they will receive Clifutinib Besylate once daily repeatedly until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days.

Expansion part:Expansion cohort might be set to further investigate the safety and efficacy of Clifutinib Besylate at or lower MTD dose recommended by dose-escalation part.

Eligibility criteria: Inclusion Criteria:

* Documented acute myeloid leukemia according to World Health Organization（WHO） criteria(excluding acute promyelocytic leukemia), with FLT3-ITD gene mutation,refractory after common or enhanced chemotherapy or relapse.
* ECOG performance status of 0-1.
* Subjects must have adequate organ function and meeting all of the following laboratory review before enrollment：

  * Lood routine examination: WBC≤2000/mm3;
  * Liver function: Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤2.5×upper limit of normal(ULN); serum bilirubin ≤ 1.5 × ULN;
  * Renal function: Serum creatinine ≤ 1.5×ULN, or the creatinine clearance (CrCl)≥ 60 mL / min calculated by the Cockcroft-Gault formula;
  * Electrolyte: serum potassium≥3.0mmol/L; serum calcium≥2.0 mmol/L;serum magnesium≥0.5 mmol/L;
  * Coagulation function:fibrinogen≥1.0g/L; activated partial thromboplastin time( APTT)≦ULN+10s; prothrombin time(PT)≤ULN+3s.

Exclusion Criteria:

* Received FLT3 inhibitors within 4 weeks prior to the administration;
* Received hematopoietic stem cell transplantation within2 months prior to the administration or received immunosuppressor beceause of GVHD;
* Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to administration;
* Nitrosourea and mitomycin chemotherapy within 6 weeks prior to the administration;
* Have taken live vaccines within 4 weeks prior to /or concurrent with the administration;
* Have received a trial investigational product, or participated in other clinical trials within 4 weeks prior to administration;
* Documented promyelocytic leukemia (t (15; 17) (q22; q11) and / or promyelocytic leukemia(PML)/retinoic acid receptor alpha (RARa) positivity found in the chromosome, variant acute promyelocytic leukemia;
* With myeloid sarcoma or invasion of central nervous system;
* NCI CTCAE 4.03 ≥ 2 grade of arrhythmia, or corrected QT interval(QTc )\> 450 ms ; patients with a history of torsion or congenital QT prolonged syndrome; active infectious disease judged by the investigator.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: day 1-28
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: On day 1,8,15,22,28
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: On day 1,8,15,22,28
measure: Area under the plasma concentration time curve
timeFrame: On day 1,8,15,22,28
measure: Composite CR rate
timeFrame: up to 18 months
measure: Duration of response
timeFrame: up to 18 months
measure: Objective response rate
timeFrame: up to 18 months
measure: Event Free Survival
timeFrame: up to 18 months
measure: Overall Survival
timeFrame: up to 18 months
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: the First Affiliated Hospital,College of Medicine,Zhejiang University
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: Jie Jin, Doctor
role: STUDY_CHAIR
References: