A Phase II Study of Flumatinib Versus Imatinib to Treat Philadelphia Chromosome Positive Chronic Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01503502
First received: January 1, 2012
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

It is an open-label, randomized, multi-center study. The efficacy and safety of two flumatinib doses, 400 mg once daily and 600 mg once daily, will be compared with imatinib 400 mg once daily in newly diagnosed (within 6 months) patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).


Condition Intervention Phase
Myelogenous Leukemia, Chronic
Drug: flumatinib
Drug: imatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Flumatinib Versus Imatinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Resource links provided by NLM:


Further study details as provided by Jiangsu HengRui Medicine Co., Ltd.:

Primary Outcome Measures:
  • To compare the rate of MMR at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Obtain major molecular response (MMR) rate at 6 months in newly diagnosed Ph+ CML patients through comparison of the efficacy results of flumatinib with that of imtinib.


Secondary Outcome Measures:
  • To compare the rate of MMR at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: flumatinib 400mg qd Drug: flumatinib
Flumatinib was supplied as 100 and 200 mg film-coated tablets for oral administration. Storage condition: 25°C, light proof, sealed.
Other Name: HHGV678
Experimental: flumatinib 600 mg qd Drug: flumatinib
Flumatinib was supplied as 100 and 200 mg film-coated tablets for oral administration. Storage condition: 25°C, light proof, sealed.
Other Name: HHGV678
Active Comparator: imatinib Drug: imatinib
Imatinib was supplied as 100 mg film-coated tablets. Storage condition: 25°C (77°F). Protected from moisture.
Other Name: Gleevec

Detailed Description:

It is an open-label, randomized, multi-center study in comparison of Gleevec and flumatinib in newly diagnosed (within 6 months) CML patients who are Philadelphia chromosome-positive. One hundred and fifty adult patients will be randomized in 1:1:1 ratio. The planned doses are as follows: 400 mg QD (50 patients) of flumatinib, 600 mg QD (50 patients) of flumatinib, and 400 mg QD (50 patients) of imatinib. Flumatinib will be dosed, based on the food effect results, in fasting condition. Imatinib will be dosed with food per the package insert. The study consists of 2 phases: 6 months of core phase and 6 months of extension phase.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients ≥ 18 years and ≤ 75 years of age.
  2. ECOG 0, 1, or 2.
  3. Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome.
  4. Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis.
  5. Adequate end organ function as defined by:

    1. Total bilirubin < 1.5 x ULN,
    2. SGOT and SGPT < 2.5 x ULN,
    3. Creatinine < 1.5 x ULN,
    4. Serum amylase and lipase ≤ 1.5 x ULN,
    5. Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.

    And patients must have the following laboratory values (≥ LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication.):

    1. Potassium ≥ LLN,
    2. Magnesium ≥ LLN,
    3. Phosphorus ≥ LLN,
    4. Total calcium (corrected for serum albumin) ≥ LLN.
  6. Signed informed consent.

Exclusion Criteria:

  1. Previously documented T315I mutations.
  2. Any medical treatment for CML prior to study entry with the exception of hydroxyurea and/or anagrelide. Treatment with tyrosine kinase inhibitor(s) prior to study entry is not allowed.
  3. Treatment with other investigational agents (defined as not used in accordance with the approved indication ) within 4 weeks prior to randomization.
  4. Major surgery within 4 weeks prior to randomization or who have not recovered from prior surgery.
  5. Impaired cardiac function including any one of the following:

    1. History of unstable angina.
    2. History of clinically documented myocardial infarction (during the last 12 month).
    3. LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by locally read echocardiogram.
    4. Inability to determine the QT interval on ECG.
    5. Complete left bundle branch block.
    6. Use of a ventricular-paced pacemaker.
    7. Congenital long QT syndrome or a known family history of long QT syndrome.
    8. History of or presence of clinically significant ventricular, atrial tachyarrhythmias, or QTcF > 450 msec for male or 470 msec for female.
  6. Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders.
  7. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
  8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
  9. History of significant congenital or acquired bleeding disorder unrelated to cancer.
  10. History of chronic pancreatitis or history of acute pancreatitis within 1 year of study entry.
  11. Patients with another primary malignancy.
  12. Acute or chronic uncontrolled liver or severe renal disease considered unrelated to disease.
  13. Known to be allergic to the study drugs, including crude drug or adjuvant.
  14. Patients actively receiving therapy with strong CYP3A4 inhibitors, strong CYP3A4 inducers or any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  15. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test within 7 days prior to Day 1 of study and (d) female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01503502

Locations
China, Beijing
Peking University People's Hospital
Beijing, Beijing, China, 100044
China, Hubei
Union Hospital Tongji Medical College Huazhong University of Science and technology
Wuhan, Hubei, China, 430022
China, Jiangsu
The First Rffiurted Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
China, Shanghai
Ruijin Hospital
Shanghai, Shanghai, China, 200025
China, Tianjin
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin, China, 300020
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
Principal Investigator: Jianxiang Wang, Dr. Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Principal Investigator: Fengkui Zhang, Dr. Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
  More Information

No publications provided

Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT01503502     History of Changes
Other Study ID Numbers: HHGV678-201
Study First Received: January 1, 2012
Last Updated: April 9, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
Myelogenous Leukemia
chronce
Philadelphia Chromosome Positive
Flumatinib

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Abnormal Karyotype
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Disease Attributes
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014