Clinical Trials /

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

NCT03883087

Description:

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).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Pivotal Study of HQP1351 in Patients of Chronic Myeloid Leukemia in Chronic Phase With T315I Mutation
  • Official Title: A Phase II Multi-center, Open Label Study of HQP1351 in Chinese Patients of Chronic Myeloid Leukemia With T315I Mutation in Chronic Phase

Clinical Trial IDs

  • ORG STUDY ID: HQP1351CC201
  • NCT ID: NCT03883087

Conditions

  • Chronic Myeloid Leukemia, Chronic Phase

Interventions

DrugSynonymsArms
HQP1351HQP1351

Purpose

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).

Detailed Description

      This is an open, single-arm, multi-center phase 2 clinical study to evaluate the efficacy and
      safety of oral administrated HQP1351(40mg, QOD) in CML-CP patients with T315I mutation in
      China. A total of 40 CML-CP patients will be included in this pivotal study. After screening,
      eligible subjects will receive oral HQP1351 40mg on a continues once every other day dosing
      regimen , until disease progression, drug intolerance, or meet other treatment conditions to
      discontinue the study. During the course of treatment, each subject will be assessed
      regularly for hematological, cytogenetic and molecular responses. At the same time, safety
      information also will be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
HQP1351Experimental
  • HQP1351

Eligibility Criteria

        Inclusion Criteria:

          1. Male or non-pregnant, non-lactating female patients who are 18 years of age or older.

          2. CML-CP patients with positive Ph chromosome or BCR-ABL fusion genes.

          3. After any targeted BCR-ABL1 tyrosine kinase inhibitors (TKI) treatment, CML-CP
             patients with T315I mutation.

          4. 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.

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

          6. Predicted life expectancy of ≥3 months.

          7. 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.

               -  PT、APTT、INR≤1.5×ULN.

          8. Cardiac function index: ejection fraction (EF) > 50%, pulmonary arterial systolic
             pressure (PASP) ≤50 mmHg.

          9. Corrected QT interval (QTc) on electrocardiogram (ECG) evaluation: QTc≤450ms in males
             or ≤470ms in females.

         10. Males and females of childbearing potential and their partners voluntarily take
             contraceptive measures that the researchers believe are effective within 120 days from
             the signing of the informed consent to the last use of the research drug, or confirm
             that sterilization has been performed (at least one month before screening).

         11. Willingness and ability to comply with study procedures and follow-up examination.

        Exclusion Criteria:

          1. 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.

          2. The patients who received any other investigating drugs within 14 days prior to first
             administration.

          3. Patients who have progressed to accelerated phase (AP) or blast phase (BP) in the
             past.

          4. Patients who are currently receiving treatment with a medication that has the
             potential to interact with research drug

          5. Have previously been treated with ponatinib or HQP1351 (or drugs of similar
             composition).

          6. Absorption disorder syndrome or other diseases affecting oral drug absorption.

          7. 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.

          8. Pulmonary systolic pressure (PSP) of echocardiography is more than 50 mmHg, or there
             is clinical symptom related to pulmonary hypertension.

          9. 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.

         10. Underwent autologous or allogeneic stem cell transplant.

         11. CML-CP patient currently diagnosed as Complete cytogenetic remission (CCyR).

         12. 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.

         13. 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.

         14. 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).

         15. Have active nervous system (CNS) disease as evidence by cytology or pathology. In the
             absence of clinical CNS disease, lumbar puncture is not required.

         16. History of another primary malignancies.

         17. Active symptomatic infection.

         18. Known to be allergic to study drug ingredients or their analogues.

         19. Female patients with blood β-Human chorionic gonadotropin (HCG)positive, pregnant or
             lactating or expecting pregnancy during the study program.

         20. Suffer from any condition or illness that, in the opinion of the Investigator or the
             medical monitor, would compromise patient safety or interfere with the evaluation of
             the safety of the research drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major cytogenetic response (MCyR)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Complete cytogenetic response (CCyR)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:CCyR is the proportion of patients achieving CCyR after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.
Measure:Complete hematologic response (CHR)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:CHR requires that all of the following are present: white blood cell<10×10E9/ liter; blood platelet count<450×10E9/ liter; no medullary immature granulocytes in the peripheral blood (such as protocell, promyelocyte and myelocyte); basophils in peripheral blood are less than 5%; no disease symptoms, signs and palpable splenomegaly has disappeared; the duration of the above criteria is no less than 4 weeks. We will calculate the proportion of patients achieving CHR after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.
Measure:Major molecular response (MMR)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:MMR is the proportion of patients achieving a ratio of ≤0.1% breakpoint cluster region (BCR) abelson leukemia (ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL[IS]) after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.
Measure:BCR-ABL1(IS) transcript ≤1%
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:BCR-ABL1(IS) ≤1% is the proportion of patients achieving BCR-ABL1(IS) ≤1% by quantitative polymerase chain reaction detection. It is defined as the best response obtained by the subjects during the whole treatment process of the study.
Measure:Time to response
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:The time to response is defined as the interval between the first use of HQP1351 and the first date at which the criteria for response are met. The subject who isn't met the response criteria will be censored at the last assessment time.
Measure:Duration of response
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:Duration of response is defined as the interval between the first assessment at which the criteria for response are met until the earliest date at which the criteria for progression are met, and the subject who isn't met the progression criteria will be censored at the last assessment time. The duration of response is calculated only for subjects who achieved response.
Measure:Progression free survival (PFS)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:PFS is defined as the interval between the first dose date of HQP1351 treatment and the first date at which the criteria for progression are met, or death. The subject who isn't progression or death will be censored at the last response assessment.
Measure:Overall survive (OS)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:OS is defined as the interval between the first dose date of HQP1351 treatment and date of death, censored at the last contact date to be alive.
Measure:Safety: adverse events (AEs), and serious AEs (SAEs)
Time Frame:By the end of Cycle 24 (each cycle is 28 days)
Safety Issue:
Description:Patients with HQP1351 treatment related AE, SAE will be assessed according NCI CTCAE Version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

Trial Keywords

  • Chronic Myeloid Leukemia,CML
  • T315I mutation
  • TKI
  • CML-CP
  • HQP1351

Last Updated