A Phase Ⅰb/Ⅱ Clinical Study of Clifutinib Besylate Combined With Chemotherapy in the Treatment of Newly Diagnosed AML

A Phase Ib/II, Multi-center, Open Clinical Trial of Crifortinib Besylate Combined With Chemotherapy in Newly-treated Adult Subjects With Acute Myeloid Leukemia

This is a multi-center open clinical study aimed at evaluating the efficacy and safety of Clifutinib Besylate combined with chemotherapy in newly-treated adult subjects with AML

Study Overview

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

Detailed Description

Main purpose:To evaluate the tolerability and safety of Clifutinib Besylate combined with DA (Cytarabine + Daunorubicin) or AZA (Azacitidine) in newly-treated adult AML subjects; explore reasonable therapeutic doses through climbing tests in different dose groups.

To evaluate the efficacy of Clifutinib Besylate combined with DA or AZA in newly treated adult AML subjects.

Secondary purpose:To observe the pharmacokinetic (PK) characteristics of Clifutinib combined with DA or AZA in newly-treated adult AML subjects and the drug interaction between Clifutinib and AZA at the same time.Observe the correlation of different subtypes and prognostic risk with the efficacy of Clifutinib and the changes of genes before and after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 133
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310003
      • 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

Description

Inclusion Criteria:

• 1.Cohort 1: 18 years old ≤ age ≤65 years old;Cohort 2: The dose escalation trial only included AML subjects aged ≥60 years; the extended trial included subjects who were ≥60 years old or between 18 and 59 years old (including 18 and 59 years old) and could not tolerate strong chemotherapy.

  2.It can be primary AML or AML secondary to MDS, and has not been treated; the extension phase requires the subject to be positive for the FLT3-ITD mutation.

  3.The ECOG score according to the requirements of different groups is as follows: Cohort 1: 0~1 points; Cohort 2: Age ≥60 years old: 0~2 points; Age 18~59 years old (including 18 and 59 years old): 0~3 points.

  4.Expected survival time ≥ 12 weeks. 5. Subjects must have adequate organ function. 6.subjects voluntarily participated in the study, and signed a written informed consent form by themselves or their guardians.

Exclusion Criteria:

• 1.Diagnosed as APL and manifested as t(15;17)(q22;q12) chromosomal translocation, or BCR-ABL positive leukemia；Diagnosed as secondary to AML due to previous chemotherapy or radiotherapy of other tumors; previously received FLT3 inhibitor.

  2.AML secondary to myeloproliferative tumor (MPN) or acute lymphoblastic leukemia (ALL).

  3.Subjects who have infiltrated the central nervous system in the past or present.

  4.Concomitant with other malignant tumors within 5 years before the first medication.

  5.Thrombosis or embolism occurred within 12 months before the first medication. 6.Pulmonary function tests indicate that subjects have DLCO ≤50% or FEV1 ≤60%, or have difficulty breathing during rest or require continuous oxygen inhalation.

  7.Subjects with uncontrollable, active infections。 8.Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or subjects undergoing total gastrectomy。 9.Subjects with a history of psychotropic drug abuse and unable to quit or those with mental disorders。 10.Researchers believe that those who have other severe acute or chronic diseases who are not suitable for participating in clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Queue 1:Clifutinib Besylate:30mg qd d8-21;Daunorubicin 60 mg/m2 qd d1-3;Cytarabine 100 mg/m2 qd d1-7 Queue 1:Clifutinib Besylate:30mg qd d1-28 ;Azacitidine 75 mg/m2 qd d1-7	Drug: Clifutinib Besylate; The queue 1 is divided into Induction therapy and Consolidation therapy and Maintenance treatment The queue 2 will receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs; Other Names: HEC73543
Experimental: Arm 2; Queue 1:Clifutinib Besylate:40mg qd d8-21;Daunorubicin 60 mg/m2 qd d1-3;Cytarabine 100 mg/m2 qd d1-7 Queue 1:Clifutinib Besylate:40mg qd d1-28 ;Azacitidine 75 mg/m2 qd d1-7	Drug: Clifutinib Besylate; The queue 1 is divided into Induction therapy and Consolidation therapy and Maintenance treatment The queue 2 will receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs; Other Names: HEC73543
Experimental: Arm 3; Queue 1:Clifutinib Besylate:60mg qd d8-21;Daunorubicin 60 mg/m2 qd d1-3;Cytarabine 100 mg/m2 qd d1-7 Queue 1:Clifutinib Besylate:60mg qd d1-28 ;Azacitidine 75 mg/m2 qd d1-7	Drug: Clifutinib Besylate; The queue 1 is divided into Induction therapy and Consolidation therapy and Maintenance treatment The queue 2 will receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs; 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
Composite CR rate	CR + CRi +CRMRD-	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	The time from receive CR / CRi/CRMRD-/PR to relapse	up to 12 months
Objective response rate	CR + CRi +CRMRD- + PR	up to 12 months
Event Free Survival	From the first time taking experimental drug to treatment failure or progression or relapse or death	up to 12 months
Overall Survival	From the first time taking experimental drug to death	up to 12 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): October 31, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: HEC73543-AML-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No