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

NCT03483948 | Terminated Phase 1

• 1 other identifier: 2017-523-00CH3
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Adverse Event (AE) monitoring of HMPL-523 in combination with azacitidine

  AE monitoring will be assessed by evaluation of study drug exposure, AEs , serious AEs, all deaths, as well as laboratory determinations and vital sign parameters.

  Measured from the first dose to within 30 days after the last dose.

• Overall response rate (ORR)

  Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), Morphologic leukemia-free state (MLFS), or partial remission(PR) per 2017 European Leukemia Net (ELN) recommendations

  Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.

Secondary Outcomes (13)

• Maximum plasma concentration (Cmax) of HMPL-523

  Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.

• The time to Cmax (peak time, Tmax) of HMPL-523

  Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.

• The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) of HMPL-523

  Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.

• Half-life (t1/2) of HMPL-523

  Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.

• Clearance (CL) of Azacitidine

  Measured on the cycle 1 day 7 and Cycle 1 day 8.

Study Arms (1)

HMPL-523 & Azacitidine

EXPERIMENTAL

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.

Drug: HMPL-523; Drug: Azacitidine

Interventions

HMPL-523 DRUG

HMPL-523 tablet

HMPL-523 & Azacitidine

Azacitidine DRUG

Azacitidine Injection

Also known as: Vidaza

HMPL-523 & Azacitidine

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subject must have confirmation of AML by WHO criteria, except for APL (M3)
• 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
• Subject must have received no prior treatment for AML with the exception of hydroxyurea
• ECOG performance status of 0-1. For dose-expansion stage, ECOG PS of 2 will also be eligible

You may not qualify if:

• Subject has received treatment of hypomethylating agent and/or chemo therapeutic agent for MDS or MPN
• Subject has known active CNS involvement or extramedullary sarcoma from AML
• 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)
• Subject has a white blood cell count \> 25 × 109/L (Hydroxyurea is permitted to meet this criterion)
• Subject with serum amylase or lipase \> the ULN
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load.
• Subject who don't have enough liver or renal function
• Subject with New York Heart Association (NYHA) Class III or greater congestive heart failure
• Subject received herbal therapy ≤ 1 week prior to initiation of study treatment
• Subject received prior treatment with any SYK inhibitors (Fostamatinib) or FLT3 inhibitor (Quizartinib) or multi-target inhibitor with SYK or FLT3 inhibition activity (Midostaurin)

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

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

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jianxiang Wang, Prof.

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: March 30, 2018
• Study Start: October 9, 2018
• Primary Completion: September 9, 2019
• Study Completion: September 9, 2019
• Last Updated: November 20, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)