Phase I Trial to Investigate Cafusertib Hydrochloride in Combination With Low Dose Cytarabine in Chinese Patients With Acute Myeloid Leukaemia (AML)

Leukemia, Myeloid, Acute Clinical Trial

Official title:

An Open Phase I Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Intravenous Cafusertib Hydrochloride in Combination With Subcutaneous Low Dose Cytarabine in Chinese Patients With Acute Myeloid Leukaemia (AML)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02140606
• Other study ID #: HS-10159-I-01
• Status: Recruiting
• Phase: Phase 1
• First received: May 12, 2014
• Last updated: May 13, 2014
• Start date: May 2014

Study information

• Verified date: May 2014
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Jianxiang Wang
• Phone: 022 239099120
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To investigate safety, tolerability of cafusertib combination with low dose cytarabine (LD-Ara-C) in Chinese patients with relapsed/refractory AML that are not eligible for conventional or intensive treatment. The dose of cafusertib will be escalated to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cafusertib in combination with LD-Ara-C in AML patients. At the same time, pharmacokinetic characteristics and preliminary efficacy of cafusertib will be observed in AML patients. To determine the recommended dosage regimen for phase II.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 0
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written informed consent consistent with Chinese Good Clinical Practice.

• Male or female patients of age >/= 18 years at the time of informed consent.

• Patients with relapsed/refractory AML ineligible for conventional or intensive treatment.

• Eastern Cooperative Oncology Group performance status score 0 - 2 at screening.

• Life expectancy of at least 3 months.

• Adequate hepatic, renal and metabolic function parameters: Serum total bilirubin =1.5 x upper limit of normal, aspartate transaminase (AST) , alanine transaminase (ALT) =2.5 x upper limit of normal; Creatinine clearance rate =60ml/min, Serum creatinine =1.0 x upper limit of normal; Relatively normal ECG(electrocardiogram), QTc<450 ms(male) ,QTc<470 ms(female); LVEF>50%.

• Patients who can comply with the trial and follow-up procedures.

Exclusion Criteria:

• Patients had received cafusertib hydrochloride or other PLK inhibitors.

• Patients with APL.

• Patients with central nervous system leukemia.

• Need to continue using cytokine therapy at screening.

• Patients participated in other clinical trials within 4 weeks prior to enrollment.

• Patient with severe infection.

• Patients with myocardial infarction had occurred within six months prior to enrollment.

• Severe heart disease, including NYHA class II cardiac dysfunction and above.

• Patients with HIV infection or acute and chronic viral hepatitis.

• Severe gastrointestinal disorders (bleeding, infection, obstruction or greater than grade 1 diarrhea).

• A previous history of neurological or psychiatric disorders, including epilepsy or dementia.

• Concomitant medications with CYP3A4 inhibitors, inducers or substrates; Women pregnant or breast feeding.

• Subject is thought unfit for this study by investigator.

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cafusertib Hydrochloride
Drug: Cafusertib Hydrochloride (d1 and 15) Cafusertib (d1 and 15 - one hour iv.v) Drug: Cytarabine Cytarabine 2 x 20 mg/d s.c. d1-15.

Locations

Country	Name	City	State
China	Hospital of Blood Diseases, Chinese Academy of Medical Sciences	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of cafusertib in combination with LDAraC based on the incidence of dose limiting toxicities		4 weeks	Yes
Secondary	Efficacy (complete remission, CR; complete remission with incomplete blood count recovery, Cri; Partial remission (PR))		minimum 4 weeks, maximum n.a.	No
Secondary	Incidence and intensity of adverse events graded according to CTCAE (version 4.0)		minimum 4 weeks, maximum n.a.	No
Secondary	Incidence of dose limiting toxicity (DLT)		4 weeks	Yes
Secondary	Pharmacokinetics of cafusertib		4 weeks	No