Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06387082
Status:
RECRUITING
Last Update Posted:
2024-06-21
First Post:
2024-04-19
Brief Title:
A Clinical Study of HMPL-506 in Patients With Hematological Malignancies
Sponsor:
Hutchmed
Organization:
Hutchmed
Study Overview
Official Title:
A Multicenter Open-Label Phase I Clinical Study to Evaluate the Safety Pharmacokinetics and Efficacy of HMPL-506 in Patients With Hematological Malignancies
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 1 multicenter open-label clinical study of HMPL-506 administered orally in the treatment of hematological malignancies Only eligible patients who provide the signed informed consent form ICF can be enrolled in this study The study consists of two phases ie a dose escalation phase and a dose expansion phase The study is expected to enroll approximately 60 to 98 patients including approximately 30 to 38 patients in the dose escalation phase and approximately 30 to 60 patients in the dose expansion phase
Detailed Description:
The study is divided into 2 Phases Dose Escalation Phase Dose Expansion Phase
Dose Escalation Phase In this phase the accelerated titration design with the modified toxicity probability interval-2 mTPI-2 design will be used for dose escalation and determination of the Maximum tolerated dose MTD Approximately 30 to 38 patients with MLL-rearranged andor NPM1-mutant relapsedrefractory Acute Myeloid Leukemia AML and Acute Lymphocytic Leukemia ALL will be enrolled in this phase
The determined starting dose of HMPL-506 ie 50 mg QD orally once daily approximately every 24 hours will be subsequently escalated to 100 mg QD 100 200 mg QD 100 300 mg QD 50 and finally 400 mg QD 33 this is an assumed dose gradient and the percentage in brackets corresponds to the dose increment from the previous dose level A modified Fibonacci design will be used for dose escalation
The dose will be escalated based on available efficacy and safety data in conjunction with preclinical pharmacodynamics PK data safety review committeesSRC meetings will be held to discuss the necessity of expanding the sample size of 1 or more selected dose groups with approximately 6 to 10 patients in each dose group to obtain a sufficient amount of safety and efficacy data In addition the SRC will determine the necessity of exploring a dose above 400 mg QD or an intermediate dose between two dose groups or other administration methods
Dose Expansion Phase The dose expansion phase will be conducted after the determination of the recommended phase 2 doseRP2D andor Maximum tolerated dose MTD and approximately 30 to 60 patients with hematological malignancies will be enrolled to further evaluate the safety tolerability and preliminary efficacy of HMPL-506 Patients enrolled in this phase will be divided into three cohorts
MLL-rearranged andor NPM1-mutant relapsedrefractory AML
MLL-rearranged relapsedrefractory ALL
Relapsedrefractory multiple myeloma MM and AML with genetic alterations such as NUP214 or NUP98 fusion
Approximately 10 to 20 patients are planned to be enrolled in each cohort Enrolled patients will receive oral dose of HMPL-506 at the RP2D in 28-day cycles until disease progressionrelapse except for patients who are assessed by the investigator as continuing receiving benefit from treatment with the investigational product death intolerable toxicity receiving another anti-tumor therapy failure to further benefit from the treatment as judged by the investigator patient withdrawal loss to follow-up or end of the study whichever comes first
Dose Escalation Phase In this phase the accelerated titration design with the modified toxicity probability interval-2 mTPI-2 design will be used for dose escalation and determination of the Maximum tolerated dose MTD Approximately 30 to 38 patients with MLL-rearranged andor NPM1-mutant relapsedrefractory Acute Myeloid Leukemia AML and Acute Lymphocytic Leukemia ALL will be enrolled in this phase
The determined starting dose of HMPL-506 ie 50 mg QD orally once daily approximately every 24 hours will be subsequently escalated to 100 mg QD 100 200 mg QD 100 300 mg QD 50 and finally 400 mg QD 33 this is an assumed dose gradient and the percentage in brackets corresponds to the dose increment from the previous dose level A modified Fibonacci design will be used for dose escalation
The dose will be escalated based on available efficacy and safety data in conjunction with preclinical pharmacodynamics PK data safety review committeesSRC meetings will be held to discuss the necessity of expanding the sample size of 1 or more selected dose groups with approximately 6 to 10 patients in each dose group to obtain a sufficient amount of safety and efficacy data In addition the SRC will determine the necessity of exploring a dose above 400 mg QD or an intermediate dose between two dose groups or other administration methods
Dose Expansion Phase The dose expansion phase will be conducted after the determination of the recommended phase 2 doseRP2D andor Maximum tolerated dose MTD and approximately 30 to 60 patients with hematological malignancies will be enrolled to further evaluate the safety tolerability and preliminary efficacy of HMPL-506 Patients enrolled in this phase will be divided into three cohorts
MLL-rearranged andor NPM1-mutant relapsedrefractory AML
MLL-rearranged relapsedrefractory ALL
Relapsedrefractory multiple myeloma MM and AML with genetic alterations such as NUP214 or NUP98 fusion
Approximately 10 to 20 patients are planned to be enrolled in each cohort Enrolled patients will receive oral dose of HMPL-506 at the RP2D in 28-day cycles until disease progressionrelapse except for patients who are assessed by the investigator as continuing receiving benefit from treatment with the investigational product death intolerable toxicity receiving another anti-tumor therapy failure to further benefit from the treatment as judged by the investigator patient withdrawal loss to follow-up or end of the study whichever comes first
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None