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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Clifutinib Besylate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jie Jin, Doctor; Phone Number: 0571-87236685; Email: jiej0503@163.com

Study Locations

• China
  • Hanzhou, China
    • Recruiting
    • The First Affiliated Hospital,College of Medicine,Zhejiang University
    • Contact: Jie Jin, Doctor; Phone Number: 0571-87236685; Email: jiej0503@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Clifutinib Besylate:10 mg	Drug: Clifutinib Besylate; receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days; Other Names: HEC73543
Experimental: Arm 2; Clifutinib Besylate:20 mg	Drug: Clifutinib Besylate; receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days; Other Names: HEC73543
Experimental: Arm 3; Clifutinib Besylate:40 mg	Drug: Clifutinib Besylate; receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days; Other Names: HEC73543
Experimental: Arm 4; Clifutinib Besylate:55 mg	Drug: Clifutinib Besylate; receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days; Other Names: HEC73543
Experimental: Arm 5; Clifutinib Besylate:70 mg	Drug: Clifutinib Besylate; receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days; Other Names: HEC73543

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Safety and Tolerability assessed through adverse events to determine maximum tolerated dose	day 1-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Time of maximum observed plasma concentration (Tmax)	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Area under the plasma concentration time curve	to assess the pharmacokinetic profile in patients with AML	On day 1,8,15,22,28
Composite CR rate	CR + CRi +CRMRD-	up to 18 months
Duration of response	The time from receive CR / CRi/CRMRD-/PR to relapse	up to 18 months
Objective response rate	CR + CRi +CRMRD- + PR	up to 18 months
Event Free Survival	From the first time taking experimental drug to treatment failure or progression or relapse or death	up to 18 months
Overall Survival	From the first time taking experimental drug to death	up to 18 months

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.
• Investigators: Study Chair: Jie Jin, Doctor, First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 30, 2023

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: PCD-DHEC73543-16-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No