A Study of SKLB1028 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

Phase I Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SKLB1028 When Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02859948
• Other study ID #: 1028201601/PRO
• Status: Recruiting
• Phase: Phase 1
• First received: June 28, 2016
• Last updated: August 4, 2016
• Start date: May 2016
• Est. completion date: January 2018

Study information

• Verified date: June 2016
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: Ting Liu, Dr.
• Phone: 86-028-85422364
• Email: liuting[@]scu.edu.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Patients will receive oral SKLB1028 for 28 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia With FLT3 Mutations.

Description:

It is open-label, dose escalation study designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered SKLB1028 as a single agent given daily for 28 days. Cohorts of 3 patients receive SKLB1028 until dose limiting toxicity is noted (DLT). At that point cohorts will expand to 6 patients until MTD is determined. Patients not experiencing DLT or significant disease progression could continue receiving SKLB1028 up to 1 year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent must be provided.

• Males and females age = 18 years;

• Histopathologically documented primary or secondary AML, as defined by WHO criteria, confirmed by pathology review at treating institution, meeting at least one of the following:

1. Refractory to at least 1 cycle of induction chemotherapy, or

2. Relapsed after at least 1 cycle of induction chemotherapy, or

3. Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;

• In the absence of rapidly progressing disease, the interval from prior treatment to time of SKLB1028 administration should be at least 2 weeks for cytotoxic agents, or at least 5 half-lives for noncytotoxic agents;

• Serum creatinine =1.5 × ULN;

• Total serum bilirubin = 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;

• Serum AST or ALT = 3.0 × ULN unless considered due to leukemic organ involvement;

• Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;

Exclusion Criteria:

• Histologic diagnosis of acute promyelocytic leukemia;

• Clinically active central nervous system leukemia;

• Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher;

• Bone marrow transplant within 100 days prior to study;

• Active, uncontrolled infection;

• Major surgery within 4 weeks prior to study;

• Radiation therapy within 4 weeks prior to study;

• Left ventricular ejection fraction =1 × ULN,or?50%. Clinically significant ECG QTc prolongation (Male: >450ms, Female: >470ms).Significant cardiac disease.

• Human immunodeficiency virus positivity;

• Active hepatitis B or C or other active liver disease;

• Women who are pregnant, lactating;

• Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• SKLB1028
SKLB1028 capsules in six doses beginning at 20 mg and rising to 200 mg.

Locations

Country	Name	City	State
China	West China Hospital,Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of dose limiting toxicity (DLT)and Adverse Event (AE)		28 Days	Yes
Secondary	Maximum serum concentration (Cmax)		28 Days	Yes
Secondary	Area under the plasma concentration-time curve (AUC) from time zero to the time point of t (AUC0-tn)		28 Days	No
Secondary	Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-inf)		28 Days	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		28 Days	No
Secondary	Apparent volume of distribution at equilibrium after oral administration(Vss/F)		28 Days	No
Secondary	Plasma Decay Half-Life (t1/2z)		28 Days	No
Secondary	Apparent Oral Clearance (CLz/F)		28 Days	No
Secondary	Average plasma or serum concentration(Cav)		28 Days	No
Secondary	changes in FLT3 mutation status in plasma		28 Days	No
Secondary	Rate of Complete Remission (CR)		28 Days	No
Secondary	Rate of partial remission (PR)		28 Days	No