A Pivotal Study of HQP1351 in Patients With Chronic Myeloid Leukemia in Chronic Phase

NCT04126681 | Completed Phase 2 DMC

• 1 other identifier: HQP1351CC203
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of this study is to evaluate the efficacy of HQP1351 in patients with chronic myeloid leukemia in chronic phase (CML-CP) who are resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors. The efficacy of HQP1351 is determined by evaluating the subjects' event free survival (EFS).

Conditions

Chronic Myeloid Leukemia, Chronic Phase

Keywords

Chronic Myeloid Leukemia; HQP1351; CML; CML-CP; Olverembatinib Tablets

Outcome Measures

Primary Outcomes (1)

• Event free survival (EFS)

  EFS is defined as any "event" occurred since randomization, such as disease progression.

  By the end of Cycle 24 (each cycle is 28 days)

Secondary Outcomes (7)

• Complete hematologic response (CHR)

  By the end of Cycle 24 (each cycle is 28 days)

• Major cytogenetic response (MCyR)

  By the end of Cycle 24 (each cycle is 28 days)

• Complete cytogenetic response (CCyR)

  By the end of Cycle 24 (each cycle is 28 days)

• Major molecular response (MMR)

  By the end of Cycle 24 (each cycle is 28 days)

• Progression free survival (PFS)

  By the end of Cycle 24 (each cycle is 28 days)

Study Arms (2)

HQP1351 therapy cohort

EXPERIMENTAL

HQP1351 40 mg, taken orally once every other day of a 28-day cycle

Drug: HQP1351

Best Available Therapy (BAT) cohort

ACTIVE COMPARATOR

Best available therapy (BAT) will be selected by the investigator for each participant.

Drug: Hydroxyurea or Interferon-based therapy; Drug: Homoharringtonine; Drug: Imatinib, Dasatinib or Nilotinib

Interventions

HQP1351 DRUG

HQP1351 is a new, bioavailable inhibitor against BCRABLWT and a broad spectrum of BCR-ABL mutants including BCR-ABLT315I

HQP1351 therapy cohort

Hydroxyurea or Interferon-based therapy DRUG

Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines.

Best Available Therapy (BAT) cohort

Homoharringtonine DRUG

Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines.

Best Available Therapy (BAT) cohort

Imatinib, Dasatinib or Nilotinib DRUG

Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines.

Best Available Therapy (BAT) cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
• CML-CP patients with positive Ph chromosome or BCR-ABL fusion genes.
• Resistance and intolerance of first- and second-generation TKIs: defined as resistance or intolerance to imatinib, nilotinib, and dasatinib.
• Ability to understand and willingness to sign a written informed consent form. The consent form must be signed by the patient prior to any study specific procedures.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Predicted life expectancy of ≥3 months.
• Organ function as indicated by the following laboratory indicators must be met (Hematological indicators require that no blood transfusion or any blood products or cytokines be used within 14 days prior to testing):
• Hemoglobin ≥8.0g/dL.
• White blood cell count ≥ 3.0×10\^9/L.
• Platelet count ≥ 75×10\^9/L.
• Serum creatinine ≤ 1.5×upper limit of normal (ULN) or 24 hours calculated creatinine clearance ≥ 50mL/min when serum creatinine \>1.5×ULN.
• Serum albumin ≥ 3.0 g/dL.
• Total bilirubin ≤ 1.5 x ULN.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• Amylase≤1.5×ULN. Lipase≤1.5×ULN.

You may not qualify if:

• Received cytotoxic chemotherapy or radiotherapy within 28 days prior to the first administration, interferon or cytarabine or antitumor effect Chinese herbal medicine or Chinese patent medicine within 14 days prior to the first administration, or targeted BCR-ABL1 TKI within 7 days prior to the first administration, or hydroxyurea or anagrelide within 24 hours after the first administration, or adverse events (except alopecia) caused by previous treatment and have not recovered.
• The patients who received any other investigating drugs within 14 days prior to first administration.
• For patients with CML-CP, if they have progressed to AP or BP, they cannot be enrolled after treatment with CML-CP.
• Patients who are currently receiving treatment with a medication that has the potential to interact with research drug.
• Have previously been treated with ponatinib or HQP1351 (or drugs of similar composition).
• Absorption disorder syndrome or other diseases affecting oral drug absorption.
• Have any history of heart or vascular disease, such as hypertension (systolic blood pressure (HBP) \> 140mmHg and/or diastolic blood pressure \> 90mmHg), or take medications that are known to cause QT interval prolongation. The patients with well controlled HBP can be included.
• Pulmonary systolic pressure (PSP) of echocardiography is more than 50 mmHg, or there is clinical symptom related to pulmonary hypertension.
• Have a history of serious cardiovascular diseases during the previous treatment of chronic myeloid leukemia with TKI, including myocardial infarction, unstable angina pectoris, severe arrhythmia and congestive heart failure.
• Underwent autologous or allogeneic stem cell transplant.
• CML-CP patient currently diagnosed as Complete cytogenetic response (CCyR).
• Have diseases with abnormal bleeding and coagulation function, or have a bleeding disorder unrelated to CML within 3 months before first dose of study drug.
• Underwent major surgery (except minor surgical procedures, such as placement or bone marrow biopsy) with 14 days prior to the first dose of study drug.
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy (It is defined as a daily dose of corticosteroids less than 30 mg prednisone or the same amount of other corticosteroids within 7 days).
• Have active nervous system (CNS) disease as evidence by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• HealthQuest Pharma Inc.: collaborator

Study Sites (22)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Gongdong, China

Location

Nanfang hospital of southern medical university

Guangzhou, Guangdong, 510515, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Location

The First affiliated hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Henan Provincial Oncology Hospital

Zhengzhou, Henan, 450003, China

Location

Henan Provincial people's Hospital

Zhengzhou, Henan, China

Location

Tongji Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

The First affiliated hospital of Nanchang University

Nanchang, Jiangxi, China

Location

First Hospital of Jilin University

Changchun, Jilin, China

Location

The Affiliated hospital of Qingdao University

Qingdao, Shandong, China

Location

Qilu hospital of Shandong University

Jinan, Shangdong, China

Location

Ruijing Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200032, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine(hematology dept)

Hangzhou, Zhejiang, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine(HSCTdept)

Hangzhou, Zhejiang, China

Location

Related Publications (1)

• Jiang 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: 35982483 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

olverembatinib; Hydroxyurea; Homoharringtonine; Imatinib Mesylate; Dasatinib; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Xiaojun Huang, Professor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 15, 2019
• Study Start: October 21, 2019
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: March 3, 2025

Record last verified: 2025-02

Locations

CN (22)