A Clinical Trial to Evaluate Clifutinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia(AML)
- Registration Number
- NCT04827069
- Lead Sponsor
- Sunshine Lake Pharma Co., Ltd.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 80
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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.
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ECOG performance status of 0-1.
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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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1 Clifutinib Besylate Clifutinib Besylate:10 mg Arm 2 Clifutinib Besylate Clifutinib Besylate:20 mg Arm 3 Clifutinib Besylate Clifutinib Besylate:40 mg Arm 4 Clifutinib Besylate Clifutinib Besylate:55 mg Arm 5 Clifutinib Besylate Clifutinib Besylate:70 mg Arm 6 Clifutinib Besylate Clifutinib Besylate:100 mg
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) day 1-28 Safety and Tolerability assessed through adverse events to determine maximum tolerated dose
- Secondary Outcome Measures
Name Time Method Overall Survival up to 18 months From the first time taking experimental drug to death
Maximum observed plasma concentration (Cmax) On day 1,8,15,22,28 to assess the pharmacokinetic profile in patients with AML
Time of maximum observed plasma concentration (Tmax) On day 1,8,15,22,28 to assess the pharmacokinetic profile in patients with AML
Area under the plasma concentration time curve On day 1,8,15,22,28 to assess the pharmacokinetic profile in patients with AML
Composite CR rate up to 18 months CR + CRi +CRMRD-
Duration of response up to 18 months The time from receive CR / CRi/CRMRD-/PR to relapse
Objective response rate up to 18 months CR + CRi +CRMRD- + PR
Event Free Survival up to 18 months From the first time taking experimental drug to treatment failure or progression or relapse or death
Trial Locations
- Locations (1)
the First Affiliated Hospital,College of Medicine,Zhejiang University
🇨🇳Hanzhou, China