A Pivotal Study of HQP1351 in Patients of Chronic Myeloid Leukemia in Chronic Phase With T315I Mutation

NCT03883087 | Unknown Phase 2

• 1 other identifier: HQP1351CC201
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 10

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) harboring T315I mutation. The efficacy of HQP1351 was determined by evaluating the subjects' major cytogenetic response (MCyR).

Conditions

Chronic Myeloid Leukemia, Chronic Phase

Keywords

Chronic Myeloid Leukemia,CML; T315I mutation; TKI; CML-CP; HQP1351; Olverembatinib Tablets

Outcome Measures

Primary Outcomes (1)

• Major cytogenetic response (MCyR)

  MCyR is the proportion of patients achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow). It is defined as the best response obtained by the subjects during the whole treatment process of the study. And MCyR can only be considered as CCyR if the subject meets PCyR at baseline.

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

Secondary Outcomes (9)

• Complete cytogenetic response (CCyR)

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

• Complete hematologic response (CHR)

  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)

• BCR-ABL1(IS) transcript ≤1%

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

• Time to response

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

Other Outcomes (2)

• The relationship between mutation and efficacy.

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

• Quality of life (QOL)

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

Study Arms (1)

HQP1351

EXPERIMENTAL

Drug: HQP1351

Interventions

HQP1351 DRUG

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

HQP1351

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.
• After any targeted BCR-ABL1 tyrosine kinase inhibitors (TKI) treatment, CML-CP patients with T315I mutation.
• 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 (with Cockcroft-Gault formula).
• 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 chemotherapy or radiotherapy within 28 days prior to the first administration, interferon 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.
• Patients who have progressed to accelerated phase (AP) or blast phase (BP) in the past.
• 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 prolongation. The patients with well controlled HBP can be considered to 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 remission (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

Study Sites (10)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guandong, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

Nanfang Hospital of Southern Medical University

Guanzhou, Guangdong, 510515, China

Location

Henan Tumor Hospital

Zhengzhou, Henan, China

Location

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Tongji medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

The First Hospital Affiliated of Soochow University

Suzhou, Jiangsu, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 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

Interventions

olverembatinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; 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

Study Officials

• Xiaojun Huang, Professor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

• Qian Jiang, Professor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 20, 2019
• Study Start: April 8, 2019
• Primary Completion: May 1, 2024
• Study Completion: February 1, 2025
• Last Updated: April 3, 2023

Record last verified: 2023-03

Locations

CN (10)