Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01275196
First received: January 10, 2011
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

The study will compare the efficacy and safety of Nilotinib versus Imatinib in newly diagnosed Chinese patients with CML-CP.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Nilotinib
Drug: Imatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ENESTChina: A Phase III Multi-center, Open-label, Randomized Study of Nilotinib Versus Imatinib in Chinese 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 Novartis:

Primary Outcome Measures:
  • Rate of Major Molecular Response [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of MMR at and by scheduled time points [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Time to MMR defined as the time from the date of randomization to the date of first documented MMR.

    The rate of durable MMR at 24 months, defined as the proportion of patients who are in MMR at both 12 and 24 months and who have no confirmed loss of MMR in between those 2 time points



Enrollment: 267
Study Start Date: April 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib Drug: Nilotinib
Active Comparator: Imatinib Drug: Imatinib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of Chinese ethnicity greater than or equal to 18 years of age
  • ECOG 0, 1, or 2.
  • Patients with CML-CP (Ph+) within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). Standard conventional cytogenetic analysis must be done on bone marrow. (FISH cannot be used)
  • Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation for the presence of Philadelphia chromosome of (9;22 translocation; less than 20 metaphases may be used for diagnosis
  • Documented chronic phase CML will meet all the criteria defined by:

    • < 15% blasts in peripheral blood and bone marrow
    • < 30% blasts plus promyelocytes in peripheral blood and bone marrow
    • < 20% basophils in the peripheral blood
    • ≥ 100 x 109/L (≥ 100,000/mm3) platelets
  • No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
  • Adequate organ function as defined by:

    • Total bilirubin < 1.5 x ULN
    • SGOT and SGPT < 2.5 x ULN
    • Creatinine < 1.5 x ULN
    • Serum amylase and lipase ≤ 1.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
  • 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.):

    • Potassium ≥ LLN
    • Magnesium ≥ LLN
    • Phosphate ≥ LLN
    • Total calcium (corrected for serum albumin) ≥ LLN.
  • Ability to provide written informed consent prior to any study related screening procedures being performed.

Exclusion Criteria:

  • Patients with previously documented T315I mutations;
  • Treatment with tyrosine kinase inhibitor(s) prior to study entry is not allowed, except in the following situation: in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of Gleevec/Glivec at any dose may be prescribed to the patient but for no longer than 2 weeks in duration.
  • Treatment with IFN for more than 3 months.
  • Impaired cardiac function including any one of the following:
  • Complete left bundle branch block
  • Long QT syndrome or a known family history of long QT syndrome.
  • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (<50 beats per minute)
  • QTc > 450 msec If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
  • History of clinically documented myocardial infarction within past 12 months
  • History of unstable angina (during the last 12 months)
  • Other clinically significant heart disease (e.g., congestive heart failure or uncontrolled hypertension).
  • Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
  • Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
  • History of significant congenital or acquired bleeding disorder unrelated to cancer.
  • Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
  • Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 30 days of Day 1.
  • History of non-compliance to medical regimens or inability to grant consent.
  • Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
  • Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm or reference Protocol post text appendix 1.
  • Patients actively receiving therapy with strong CYP3A4 inducers (e.g., dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John's Wort) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm or reference Protocol post text appendix 1.
  • 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)
  • History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
  • Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease.
  • 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 or switched to a different medication prior to starting study drug (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval).
  • Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline 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)

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT01275196

Locations
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510030
Novartis Investigative Site
Guangzhou, Guangdong, China, 510515
China, Hubei
Novartis Investigative Site
Wuhan, Hubei, China, 430022
China, Sichuan
Novartis Investigative Site
Chengdu, Sichuan, China, 610041
China, Tianjin
Novartis Investigative Site
Tianjin, Tianjin, China, 300020
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310003
China
Novartis Investigative Site
Beijing, China, 100044
Novartis Investigative Site
Fuzhou, China, 350001
Novartis Investigative Site
Jinan, China, 250012
Novartis Investigative Site
Nan Jing, China, 210008
Novartis Investigative Site
Shanghai, China, 200025
Novartis Investigative Site
Shanghai, China, 200433
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01275196     History of Changes
Other Study ID Numbers: CAMN107ECN02
Study First Received: January 10, 2011
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration
China: Food and Drug Administration

Keywords provided by Novartis:
Newly diagnosed,
Ph+ chronic myeloid leukemia,
CML-CP

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014