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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: SKLB1028

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital,Sichuan University
      • Contact: Ting Liu, Dr.; Phone Number: 86-028-85422364; Email: liuting@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SKLB1028; SKLB1028 capsules in six doses beginning at 20 mg and rising to 200 mg.	Drug: SKLB1028; SKLB1028 capsules in six doses beginning at 20 mg and rising to 200 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of dose limiting toxicity (DLT)and Adverse Event (AE)	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum serum concentration (Cmax)	28 Days
Area under the plasma concentration-time curve (AUC) from time zero to the time point of t (AUC0-tn)	28 Days
Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-inf)	28 Days
Time to Reach Maximum Observed Plasma Concentration (Tmax)	28 Days
Apparent volume of distribution at equilibrium after oral administration（Vss/F）	28 Days
Plasma Decay Half-Life (t1/2z)	28 Days
Apparent Oral Clearance (CLz/F)	28 Days
Average plasma or serum concentration(Cav)	28 Days
changes in FLT3 mutation status in plasma	28 Days
Rate of Complete Remission (CR)	28 Days
Rate of partial remission (PR)	28 Days

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Ting Liu, Dr., West China Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: June 28, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 9, 2016

Study Record Updates

• Last Update Posted (Estimate): August 9, 2016
• Last Update Submitted That Met QC Criteria: August 4, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 1028201601/PRO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO