A Clinical Trial to Evaluate Clifutinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia(AML)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
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| 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:
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| 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:
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| 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:
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| 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:
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) [day 1-28]
Safety and Tolerability assessed through adverse events to determine maximum tolerated dose
Secondary Outcome Measures
- 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
- Overall Survival [up to 18 months]
From the first time taking experimental drug to death
Eligibility Criteria
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.
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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：
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Lood routine examination: WBC≤2000/mm3;
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Liver function: Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤2.5×upper limit of normal(ULN); serum bilirubin ≤ 1.5 × ULN;
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Renal function: Serum creatinine ≤ 1.5×ULN, or the creatinine clearance (CrCl)≥ 60 mL / min calculated by the Cockcroft-Gault formula;
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Electrolyte: serum potassium≥3.0mmol/L; serum calcium≥2.0 mmol/L;serum magnesium≥0.5 mmol/L;
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Coagulation function:fibrinogen≥1.0g/L; activated partial thromboplastin time( APTT)≦ULN+10s; prothrombin time(PT)≤ULN+3s.
Exclusion Criteria:
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Received FLT3 inhibitors within 4 weeks prior to the administration;
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Received hematopoietic stem cell transplantation within2 months prior to the administration or received immunosuppressor beceause of GVHD;
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Chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to administration;
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Nitrosourea and mitomycin chemotherapy within 6 weeks prior to the administration;
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Have taken live vaccines within 4 weeks prior to /or concurrent with the administration;
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Have received a trial investigational product, or participated in other clinical trials within 4 weeks prior to administration;
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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;
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With myeloid sarcoma or invasion of central nervous system;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | the First Affiliated Hospital,College of Medicine,Zhejiang University | Hanzhou | China |
Sponsors and Collaborators
- Sunshine Lake Pharma Co., Ltd.
Investigators
- Study Chair: Jie Jin, Doctor, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PCD-DHEC73543-16-001