Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL
A Phase Ib Study of the Pharmacokinetics, Safety and Efficacy of Orally Administered HQP1351 in Subjects With Refractory Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
1 other identifier
interventional
242
2 countries
9
Brief Summary
A multi-center, open-label, randomized, phase Ib study to evaluate the pharmacokinetics (PK) of HQP1351 and to determine the recommended phase 2 dose (RP2D) of HQP1351 in subjects with CML chronic phase (CP), accelerated phase (AP), or blast phase (BP) or with Ph+ ALL, who have experienced resistance or intolerance to at least two tyrosine kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (CML LBP), who have experienced resistance or intolerance to at least one second or later generation TKI.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2020
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 18, 2019
CompletedStudy Start
First participant enrolled
January 9, 2020
CompletedFirst Posted
Study publicly available on registry
February 7, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 27, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2030
November 5, 2025
November 1, 2025
10 years
September 18, 2019
November 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Plasma Concentration (Cmax) of HQP1351
To evaluate the Maximum Plasma Concentration (Cmax) of HQP1351
28 days
Area Under the Curve (AUC) of HQP1351
To evaluate the Area Under the Curve (AUC) of HQP1351
28 days
Study Arms (4)
Cohort A
EXPERIMENTALCohort B
EXPERIMENTALCohort C
EXPERIMENTALCohort D
EXPERIMENTALInterventions
HQP1351 taken by mouth every other day
Administered in all patients as a continuous IV infusion at the dosage of 28μg daily (9μg daily for Cycle 1 Day 1 to Day 7).
Eligibility Criteria
You may qualify if:
- For HQP1351 monotherapy, patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, with or without T315I mutation
- For Cohort D, patients with Ph+ BCP ALL or CML LBP must be resistant or intolerant to at least one second or later generation TKI, such as dasatinib, nilotinib, bosutinib and ponatinib, despite optimal supportive care
- For HQP1351 monotherapy only: Be previously treated with and developed resistance or intolerance to at least two TKIs including ponatinib, imatinib, dasatinib, nilotinib, bosutinib, and asciminib. For patients with a T315I mutation, number of pretreated TKIs is not restricted.
- The definition of resistance to first-line TKI treatment refers to European Leukemia Net (ELN) recommendations. The definitions are the same for patients in CP, AP, BP, and Ph+ ALL, and apply also to second-line treatment, when first-line treatment was changed for intolerance. The patients must meet at least one criterion:
- Three months after the initiation of therapy: non-complete hematologic response (CHR) and/or Ph+ \>95%
- Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>35%
- Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>0%
- Then, and at any time after the initiation of therapy: Loss of CHR, or loss of complete cytogenetic response (CCyR), or confirmed loss of major molecular response (MMR) (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), mutations, clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)
- The definition of resistance to second-line TKI treatment
- a) For CML CP patients: the patients must meet at least one criterion as follows:
- i.) Three months after the initiation of therapy: No CHR or Ph+ \>95% or new mutations
- ii.) Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>65% and/or new mutations
- iii.) Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>35% and/or new mutations
- iv.) Then, and at any time after the initiation of therapy: Loss of CHR or loss of CCyR, new mutations, confirmed loss of MMR (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)
- b) For CML AP patients: the patients must meet at least one criterion as follows:
- +24 more criteria
You may not qualify if:
- Received TKI therapy within 5 half-lives or 7 days prior to first dose of HQP1351, whichever is shorter, or any adverse events (AEs) (except alopecia and pigmentation) not recovered to CTCAE v5.0 grade 0-1 due to any other treatments
- Received other therapies as follows:
- For CP and AP patients, received hydroxyurea or anagrelide within 24 hours prior to the first dose of HQP1351; or, interferon, immunotherapy or cytarabine within 14 days prior to the first dose of HQP1351; or, any other radiotherapy, cytotoxic chemotherapy or investigational therapy within 28 days prior to receiving the first dose of HQP1351
- For BP patients, received chemotherapy within 7 days prior to the first dose of HQP1351
- For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of HQP1351, or received chemotherapy within 7 days prior to the first dose of HQP1351
- Patients who are currently receiving treatment with a medication that has the potential to interact with HQP1351
- Patients who had been treated with HQP1351
- Patients requiring immunosuppressive therapy other than short time of steroid
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of study drugs
- Patients with cardiovascular diseases, including uncontrolled high blood pressure (HBP) (that is blood pressure \>140/90mmHg.); or, receiving drugs that can cause prolonged QT interval. Patients with well controlled HBP can be considered to be included. ("well controlled HBP" is defined as: HBP can be ≤ 140/90mmHg with antihypertensive treatment). Those requiring 3 or more antihypertensive medications should be discussed with the medical monitor.
- Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- Any history of myocardial infarction (MI) within 6 months or unstable angina within 3 months
- Any history of cerebrovascular accident within 1 year, or transient ischemic attack (TIA) within 3 months
- Any history of peripheral vascular infarction, including visceral infarction within 6 months
- Congestive heart failure (CHF) (New York Heart Association \[NYHA\] class III or IV) within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
City of Hope
Duarte, California, 91010, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Augusta Cancer Center
Augusta, Georgia, 30912, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Related Publications (2)
Jabbour E, Oehler VG, Koller PB, Jamy O, Lomaia E, Hunter AM, Uspenskaya O, Samarina S, Mukherjee S, Cortes JE, Baer MR, Zherebtsova V, Shuvaev V, Turkina A, Davydkin I, Guo H, Chen Z, Fu T, Jiang L, Wang C, Wang H, Yang D, Zhai Y, Kantarjian H. Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial. JAMA Oncol. 2025 Jan 1;11(1):28-35. doi: 10.1001/jamaoncol.2024.5157.
PMID: 39570620DERIVEDJiang Q, Li Z, Qin Y, Li W, Xu N, Liu B, Zhang Y, Meng L, Zhu H, Du X, Chen S, Liang Y, Hu Y, Liu X, Song Y, Men L, Chen Z, Niu Q, Wang H, Lu M, Yang D, Zhai Y, Huang X. Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. J Hematol Oncol. 2022 Aug 18;15(1):113. doi: 10.1186/s13045-022-01334-z.
PMID: 35982483DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Yifan Zhai, MD, PhD
Ascentage Pharma Group Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2019
First Posted
February 7, 2020
Study Start
January 9, 2020
Primary Completion (Estimated)
December 27, 2029
Study Completion (Estimated)
March 31, 2030
Last Updated
November 5, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share