A Clinical Trial to Evaluate Clifutinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia(AML)

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04827069
• Other study ID #: PCD-DHEC73543-16-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 18, 2018
• Est. completion date: March 30, 2023

Study information

• Verified date: August 2022
• Source: Sunshine Lake Pharma Co., Ltd.
• Contact: Jie Jin, Doctor
• Phone: 0571-87236685
• Email: jiej0503[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Clifutinib Besylate
receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days

Locations

Country	Name	City	State
China	the First Affiliated Hospital,College of Medicine,Zhejiang University	Hanzhou

Sponsors (1)

Lead Sponsor	Collaborator
Sunshine Lake Pharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	Safety and Tolerability assessed through adverse events to determine maximum tolerated dose	day 1-28
Secondary	Maximum observed plasma concentration (Cmax)	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Secondary	Time of maximum observed plasma concentration (Tmax)	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Secondary	Area under the plasma concentration time curve	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Secondary	Composite CR rate	CR + CRi +CRMRD-	up to 18 months
Secondary	Duration of response	The time from receive CR / CRi/CRMRD-/PR to relapse	up to 18 months
Secondary	Objective response rate	CR + CRi +CRMRD- + PR	up to 18 months
Secondary	Event Free Survival	From the first time taking experimental drug to treatment failure or progression or relapse or death	up to 18 months
Secondary	Overall Survival	From the first time taking experimental drug to death	up to 18 months