Phase I Study of HMPL-523+Azacitidine in Elderly Patients With Acute Myeloid Leukemia

NCT ID: NCT03483948

Last Updated: 2019-11-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-09
• Study Completion Date: 2019-09-09

Brief Summary

This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in previously untreated elderly patients with AML who are not eligible for standard induction therapy.

Detailed Description

There are two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2).

Dose-escalation stage (stage 1):

The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and maximum tolerated dosage determination. Approximately 12 to 18 dose limited toxicities evaluable patients will be enrolled. A dose of HMPL-523 up to 800mg will be taken orally once daily continuously through a 28-day Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle.

Dose-expansion stage (stage 2):

This phase is to further evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in approximately 28 previously untreated elderly patients with AML. Patients will receive HMPL-523 in combination with Azacitidine in a 28-day cycle continuously until disease progression/relapse, death, or intolerable toxicity, whichever comes first.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HMPL-523 & Azacitidine

HMPL-523 will be taken orally once daily continuously through a 28-days Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle.

Group Type: EXPERIMENTAL

HMPL-523

Intervention Type: DRUG

HMPL-523 tablet

Azacitidine

Intervention Type: DRUG

Azacitidine Injection

Interventions

HMPL-523

HMPL-523 tablet

Intervention Type: DRUG

Azacitidine

Azacitidine Injection

Intervention Type: DRUG

Other Intervention Names

Vidaza

Eligibility Criteria

Inclusion Criteria

1. Subject must have confirmation of AML by WHO criteria, except for APL (M3)

2. Subject must be ≥ 65 years of old and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors

3. Subject must have received no prior treatment for AML with the exception of hydroxyurea

4. ECOG performance status of 0-1. For dose-expansion stage, ECOG PS of 2 will also be eligible

Exclusion Criteria

1. Subject has received treatment of hypomethylating agent and/or chemo therapeutic agent for MDS or MPN

2. Subject has known active CNS involvement or extramedullary sarcoma from AML

3. Subject has favorable risk cytogenetics as categorized by the NCCN Guidelines Version 1, 2018 for Acute Myeloid Leukemia, such as inv(16) or t(16;16) or t(8;21) or t(15;17)

4. Subject has a white blood cell count > 25 × 109/L (Hydroxyurea is permitted to meet this criterion)

5. Subject with serum amylase or lipase > the ULN

6. Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load.

7. Subject who don't have enough liver or renal function

8. Subject with New York Heart Association (NYHA) Class III or greater congestive heart failure

9. Subject received herbal therapy ≤ 1 week prior to initiation of study treatment

10. Subject received prior treatment with any SYK inhibitors (Fostamatinib) or FLT3 inhibitor (Quizartinib) or multi-target inhibitor with SYK or FLT3 inhibition activity (Midostaurin)

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianxiang Wang, Prof.

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences

Locations

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Countries

China

Other Identifiers

2017-523-00CH3

Identifier Type: -

Identifier Source: org_study_id