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出境医 / 临床实验 / Nilotinib for First-line Newly Diagnosed CML-CP Patients

Nilotinib for First-line Newly Diagnosed CML-CP Patients

Study Description
Brief Summary:
This is a phase IIIb, multi-centre, single-arm, open-label, prospective study investigating the efficacy and safety of nilotinib as the first-line treatment for the adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) in China. Nilotinib 300 mg BID will be provided in this study. The assessment for the primary efficacy endpoint will be performed at 18 months and the rate of patients obtaining MR4.5 will be measured at this time point. Secondary endpoints include the complete hematologic response(CHR) and the rates of major molecular reactions (MMR) by 3, 6, 9,12,18 and 24 months; event free survival (EFS); overall survival (OS).

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia, Chronic Phase Nilotinib Drug: Nilotinib Phase 3

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Nilotinib as the First-line Treatment for Patients With Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia: a Prospective Study
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : December 1, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Nilotinib Drug: Nilotinib

Nilotinib (Tasigna ®), capsules of 150 mg

Nilotinib 2 capsules of 150 mg, orally, twice daily
Outcome Measures
Primary Outcome Measures :
  1. Molecular response (MR) 4.5 at 18 months of nilotinib 300 mg twice a day [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Molecular Response 4.5 at 3, 6, 9, 12, 24 months of nilotinib [ Time Frame: 24 months ]
  2. Major Molecular Response at 3, 6, 9, 12, 24 months of nilotinib [ Time Frame: 24 months ]
  3. Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 9, 12, 24 months of nilotinib. [ Time Frame: 24 months ]
  4. Event-free survival [ Time Frame: 24 months ]
    Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.

  5. Overall survival [ Time Frame: 24 months ]
    Survival without death from any cause


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients
  • Newly diagnosed CP-CML within 6 months prior to study entry, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript)
  • Age ≥ 18 years old (no upper age limit given)
  • CML-CP defined by primordial cells in peripheral blood or bone marrow <20%, basophils in peripheral blood <20%, platelets ≥100 x 109/L(≥100,000/mm3), except for hepatosplenomegaly
  • Patient for whom treatment with Imatinib within 2 weeks is expected No other CML treatment except for hydroxyurea and/or anagrelide and/or IFN ECOG score 0 to 2
  • Organ function defined by total serum bilirubin levels < 1.5 × the upper limit of the normal range (ULN), SGOT and SGPT < 2.5 UNL, creatinine < 1.5 × ULN, amylase and lipase ≤ 1.5 × ULN and alkaline phosphatase ≤ 2.5 × ULN not directly related to the CML
  • Laboratory values defined by potassium ≥ LLN, magnesium ≥ LLN, phosphate ≥ LLN, total calcium (correction for serum albumin) ≥ LLN
  • No planned allogeneic stem cell transplantation
  • Signed informed consent

Exclusion Criteria:

  • Patients confirmed to have a T315I mutation
  • TKIs are not allowed to be treated prior to entering the study, unless the patient has an emergency pending the start of the study, and any dose of commercial imatinib may be used to the patient, but no more than 2 weeks
  • Treatment with IFN for more than 3 mouths

  • Impaired cardiac function including any of the following:

    1. Complete left bundle branch block
    2. Right bundle branch block plus left anterior hemiblock,bifascicular block
    3. Use of a ventricular-paced pacemaker
    4. Congenital long QT syndrome
    5. Clinically significant ventricular or atrial tachyarrhythmias
    6. Clinically significant resting bradycardia (<50 beats per minute)
    7. QTcF >450 msec on screening ECG.If QTcF >450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion
    8. Myocardial infarction within 12 months prior to starting nilotinib
    9. Other clinical significant heart disease (e.g. unstable angina,congestive heart failure,uncontrolled hypertension)
  • Patients who are confirmed CNS infiltration by cytopathology
  • Concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections)
  • Congenital or acquired bleeding tendency
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Received other study medications within 30 days (defined as drugs that cannot be used based on approved indications)
  • Patients unwilling or unable to comply with the protocol
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Concomitant medications known to be strong inducers or inhibitors of the CYP450 Isoenzyme CYP3A4 (for example, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, and midazolam)
  • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g.ulcerative disease,uncontrolled nausea,vomiting and diarrhea,malabsorption syndrome,small bowel resection or gastric by-pass surgery)
  • History of acute pancreatitis within 12 months or chronic pancreatitis
  • History of acute or chronic diseases of Liver, pancreas or kidney
  • Concomitant medications with potential QT prolongation
  • Patients who are pregnant or breast feeding or women of reproductive potential not employing an effective method of birth control.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib.Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential.Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
Contacts and Locations

Locations
Layout table for location information
China, Guangdong
Shenzhen Second People's Hospital Recruiting
Shenzhen, Guangdong, China, 518035
Contact: Xin Du, Phd    075583366388 ext 8196    duxingz@medmail.com.cn   
Sponsors and Collaborators
Shenzhen Second People's Hospital
Zhongshan City People's Hospital
Affiliated Hospital of Guangdong Medical University
Huazhong University of Science and Technology Union Shenzhen Hospital
Dongguan People's Hospital
Longgang District Central Hospital of Shenzhen
Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE June 1, 2019
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019) 		Molecular response (MR) 4.5 at 18 months of nilotinib 300 mg twice a day [ Time Frame: 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Molecular Response 4.5 at 3, 6, 9, 12, 24 months of nilotinib [ Time Frame: 24 months ]
  • Major Molecular Response at 3, 6, 9, 12, 24 months of nilotinib [ Time Frame: 24 months ]
  • Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 9, 12, 24 months of nilotinib. [ Time Frame: 24 months ]
  • Event-free survival [ Time Frame: 24 months ]
    Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.
  • Overall survival [ Time Frame: 24 months ]
    Survival without death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nilotinib for First-line Newly Diagnosed CML-CP Patients
Official Title  ICMJE Efficacy and Safety of Nilotinib as the First-line Treatment for Patients With Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia: a Prospective Study
Brief Summary This is a phase IIIb, multi-centre, single-arm, open-label, prospective study investigating the efficacy and safety of nilotinib as the first-line treatment for the adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) in China. Nilotinib 300 mg BID will be provided in this study. The assessment for the primary efficacy endpoint will be performed at 18 months and the rate of patients obtaining MR4.5 will be measured at this time point. Secondary endpoints include the complete hematologic response(CHR) and the rates of major molecular reactions (MMR) by 3, 6, 9,12,18 and 24 months; event free survival (EFS); overall survival (OS).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Myeloid Leukemia, Chronic Phase
  • Nilotinib
Intervention  ICMJE Drug: Nilotinib

Nilotinib (Tasigna ®), capsules of 150 mg

Nilotinib 2 capsules of 150 mg, orally, twice daily
Study Arms  ICMJE Experimental: Nilotinib
Intervention: Drug: Nilotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019) 		100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2023
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female patients
  • Newly diagnosed CP-CML within 6 months prior to study entry, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript)
  • Age ≥ 18 years old (no upper age limit given)
  • CML-CP defined by primordial cells in peripheral blood or bone marrow <20%, basophils in peripheral blood <20%, platelets ≥100 x 109/L(≥100,000/mm3), except for hepatosplenomegaly
  • Patient for whom treatment with Imatinib within 2 weeks is expected No other CML treatment except for hydroxyurea and/or anagrelide and/or IFN ECOG score 0 to 2
  • Organ function defined by total serum bilirubin levels < 1.5 × the upper limit of the normal range (ULN), SGOT and SGPT < 2.5 UNL, creatinine < 1.5 × ULN, amylase and lipase ≤ 1.5 × ULN and alkaline phosphatase ≤ 2.5 × ULN not directly related to the CML
  • Laboratory values defined by potassium ≥ LLN, magnesium ≥ LLN, phosphate ≥ LLN, total calcium (correction for serum albumin) ≥ LLN
  • No planned allogeneic stem cell transplantation
  • Signed informed consent

Exclusion Criteria:

  • Patients confirmed to have a T315I mutation
  • TKIs are not allowed to be treated prior to entering the study, unless the patient has an emergency pending the start of the study, and any dose of commercial imatinib may be used to the patient, but no more than 2 weeks
  • Treatment with IFN for more than 3 mouths

  • Impaired cardiac function including any of the following:

    1. Complete left bundle branch block
    2. Right bundle branch block plus left anterior hemiblock,bifascicular block
    3. Use of a ventricular-paced pacemaker
    4. Congenital long QT syndrome
    5. Clinically significant ventricular or atrial tachyarrhythmias
    6. Clinically significant resting bradycardia (<50 beats per minute)
    7. QTcF >450 msec on screening ECG.If QTcF >450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion
    8. Myocardial infarction within 12 months prior to starting nilotinib
    9. Other clinical significant heart disease (e.g. unstable angina,congestive heart failure,uncontrolled hypertension)
  • Patients who are confirmed CNS infiltration by cytopathology
  • Concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections)
  • Congenital or acquired bleeding tendency
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Received other study medications within 30 days (defined as drugs that cannot be used based on approved indications)
  • Patients unwilling or unable to comply with the protocol
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Concomitant medications known to be strong inducers or inhibitors of the CYP450 Isoenzyme CYP3A4 (for example, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, and midazolam)
  • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g.ulcerative disease,uncontrolled nausea,vomiting and diarrhea,malabsorption syndrome,small bowel resection or gastric by-pass surgery)
  • History of acute pancreatitis within 12 months or chronic pancreatitis
  • History of acute or chronic diseases of Liver, pancreas or kidney
  • Concomitant medications with potential QT prolongation
  • Patients who are pregnant or breast feeding or women of reproductive potential not employing an effective method of birth control.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib.Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential.Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03942094
Other Study ID Numbers  ICMJE Nilotinib20190426
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Shenzhen Second People's Hospital
Study Sponsor  ICMJE Shenzhen Second People's Hospital
Collaborators  ICMJE
  • Zhongshan City People's Hospital
  • Affiliated Hospital of Guangdong Medical University
  • Huazhong University of Science and Technology Union Shenzhen Hospital
  • Dongguan People's Hospital
  • Longgang District Central Hospital of Shenzhen
Investigators  ICMJE Not Provided
PRS Account Shenzhen Second People's Hospital
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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