Acute Myeloid Leukemia
Conditions
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.
Interventions
receive oral Clifutinib Besylate once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days
Sponsors
Sunshine Lake Pharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arm 1:10 mg Arm 2:20 mg Arm 3:40 mg Arm 4:55 mg Arm 5:70 mg Arm 6: 100 mg
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | day 1-28 | Safety and Tolerability assessed through adverse events to determine maximum tolerated dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall Survival | up to 18 months | From the first time taking experimental drug to death |
| 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 |
| Composite CR rate | up to 18 months | CR + CRi +CRMRD- |
Countries
China
Outcome results
None listed