A Study of the Efficacy and Safety of Flumatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase.

April 28, 2022 updated by: Jiangsu Hansoh Pharmaceutical Co., Ltd.

A Double-blind , Randomized, Multicenter, Phase 4 Study to Evaluate Efficacy and Safety of Oral Flumatinib 400mg Versus 600mg in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase.

It's a double-blind , randomized ,multi-center study. The purpose of this study is to explore the efficacy and safety of flumatinib 400mg once daily (QD) versus 600mg QD as the first line therapy in patients with chronic myleiod leukemia(CML) in chronic phase(CP).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a dose-optimization study of flumatinib in adult patient with newly diagnosed CML-CP. The objective of this study is to compare the efficacy and safety of flumatinib 400mg QD with that of 600mg QD. Eligible patients are randomized in a 1:1 ratio to receive either fluamtinib 400mg QD or flumatinib 600mg QD. Randomization is stratified based on Sokal risk score (<0.8,0.8~1.2,>1.2). Patients will discontinue study therapy due to treatment failure, disease progression or intolerance to study medication or due to investigator's or participant's decision. The primary efficacy endpoint is the rate of early molecular response , as measured by RQ-PCR at 3 months. Hematologic response, molecular response and cytogenetic response will be assessed at baseline and a certain frequency after treatment, until study completion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Hei Longjiang
      • Harbin, Hei Longjiang, China
        • Recruiting
        • Institute of Hematology and Oncology, Harbin The First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed informed consent form.
  2. Men or women aged more than or equal to (≥) 18 years, and less than (<) 75 years.
  3. ECOG performance status of 0-2.
  4. Patients with philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) within 6 months of diagnosis.
  5. Adequate organ function.
  6. Men or women should be using adequate contraceptive measures throughout the study; Females should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study.
  7. Females must have evidence of non-childbearing potential.

Exclusion Criteria:

  1. Known atypical CML or presence of additional chromosomal abnormalities.
  2. Known presence of the T315I mutation.
  3. Treatment with tyrosine kinase inhibitor(s) prior to randomization.
  4. Any treatment with anti-CML activity for longer than 2 weeks(exception of hydroxyurea or anagrelide) or hematopoietic stem cell transplantation prior to randomization .
  5. Prior treatment with splenectomy.

  6. Impaired cardiac function including any one of the following:

    1. Resting corrected QT interval (QTc) > 470 ms obtained from electrocardiogram (ECG), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
    2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
    3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
    4. Left ventricular ejection fraction (LVEF) ≤ 50%.
    5. During screening period, ECG examination showed average heart rate <50 beats per minute.
    6. Myocardial infarction occurred within 12 months of randomization;
    7. Congestive heart failure occurred within 6 months of randomization;
    8. Uncontrollable angina.
  7. Stroke or transient ischemic attack within 6 months of randomization.
  8. Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes).
  9. Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption.
  10. The presence of active infectious diseases has been known prior to randomization
  11. History of significant congenital or acquired bleeding disorders unrelated to CML
  12. Inadequate other organ function.
  13. History of other malignancies.
  14. History of hypersensitivity to any active or inactive ingredient of flumatinib.
  15. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued.
  16. Major surgery within 4 weeks of randomization.
  17. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 within 4 weeks of randomization.
  18. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
  19. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Flumatinib (400mg)
Flumatinib 400mg QD
Drug: Flumatinib mesylate tablets (400mg)
Flumatinib 400mg +Placebo for flumatinib are administered orally daily. Patients are randomized to flumatinib 400mg QD.
Experimental: Flumatinib (600mg)
Flumatinib 600mg QD
Drug: Flumatinib mesylate tablets (600mg)
Flumatinib 600mg is administered orally daily. Patients are randomized to flumatinib 600mg QD.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Early molecular response(EMR) rate at 3 months
Time Frame: 3 months
Molecular response is assessed using BCR-ABL transcript levels and measured by realtime quantitative polymerase chain reaction(RQ-PCR). Early molecular response is defined as a ratio BCR-ABL/ABL ≤10% on the international scale (IS).
3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Major molecular response(MMR) rate at month 3,6,9 and 12
Time Frame: 3, 6, 9 and 12 months
Major molecular response is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale as measured by RQ-PCR.
3, 6, 9 and 12 months
MR4.0 rate at month 3,6,9 and 12
Time Frame: 3, 6, 9 and 12 months
MR4.0 is defined as BCR-ABL/ABL ≤0.01% on the international scale.
3, 6, 9 and 12 months
MR4.5 rate at month 3,6,9 and 12
Time Frame: 3, 6, 9 and 12 months
MR4.5 is defined as BCR-ABL/ABL ≤0.0032% on the international scale.
3, 6, 9 and 12 months
Complete cytogenetic response（CCyR）rate at month 3,6,9 and 12
Time Frame: 3, 6, 9 and 12 months
Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample . CCyR is defined as 0% Ph+ metaphases in the bone marrow.
3, 6, 9 and 12 months
Complete hematologic response(CHR) rate at month 1,2,3,4,5,6,9 and 12
Time Frame: 1,2,3,4,5,6,9 and 12 months

Hematologic response will be assessed by complete blood count (CBC) and physical examination at each visit. CHR is defined as all of the following present:

  1. white blood cell(WBC) count <10×109/L
  2. Platelet count <450 ×109/L
  3. Peripheral blood basophils <5%
  4. No blasts and no promyelocytes in peripheral blood
  5. < 5% myelocytes plus metamyelocytes in peripheral blood
  6. No evidence of extramedullary disease, including no splenomegaly or hepatomegaly
1,2,3,4,5,6,9 and 12 months
Time to first MMR
Time Frame: up to 36 months
Evaluate the time from the date of randomization to the date of first documented MMR during treatment.
up to 36 months
Time to first CCyR
Time Frame: up to 36 months
Evaluate the time from the date of randomization to the date of first documented CCyR during treatment.
up to 36 months
Duration of MMR
Time Frame: up to 36 months
Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR.
up to 36 months
Duration of CCyR
Time Frame: up to 36 months
Duration of CCyR is defined as the time from the date of first documented CCyR to the earliest date of loss of CCyR.
up to 36 months
Event-free survival (EFS)
Time Frame: up to 36 months
EFS is defined as the time from the date of randomization to the earliest occurrence of the following events: death due to any cause ; loss of CHR ,loss of PCyR ;loss of CCyR ; discontinuation of study treatment due to AE or treatment failure ; progression to AP/BC
up to 36 months
Progression-free survival (PFS)
Time Frame: up to 36 months
PFS is defined as the time from the date of randomization to the earliest occurrence of progression to AP/BC or death from any cause.
up to 36 months
Overall survival (OS)
Time Frame: Frame:12 and 36 months
OS is defined as the time from the date of randomization to the date of death from any cause.
Frame:12 and 36 months
The incidence and severity of adverse events ((AE)
Time Frame: up to 36 months
Assessed by number and severity of adverse events as recorded on the case report form NCI CTCAE v5.0.
up to 36 months
Pharmacokinetics (PK) of HS-10096：Tmax
Time Frame: Up to approximately 36 months
Serum concentrations of HS-10096 will be collected and analyzed to evaluate the PK of HS-10096.Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).
Up to approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jun Ma, Institute of Hematology and Oncology, Harbin The First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 23, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HS-10096-402

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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