Nilotinib in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00809211
First received: December 16, 2008
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well nilotinib works in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Drug: nilotinib
Genetic: cytogenetic analysis
Genetic: mutation analysis
Genetic: polymerase chain reaction
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multi-center, Open-label, Study of Nilotinib at a Dose of 300mg Twice Daily 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 ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • Complete cytogenetic response rate at 6 months as assessed by metaphase analysis [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Molecular response rate at 3, 6, 9, 12, 18, and 24 months as assessed by quantitative PCR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Time to disease progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of event-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall toxicity rate [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Correlation of pharmacokinetic data with response rate and toxicity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Correlation of Bcr-Abl results using GeneXpert with Bcr-Abl results using international standardized quantitative PCR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Prevalence of Bcr-Abl mutations prior to and during treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2008
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib Drug: nilotinib Genetic: cytogenetic analysis Genetic: mutation analysis Genetic: polymerase chain reaction Other: pharmacological study

Detailed Description:

OBJECTIVES:

Primary

  • To establish the complete cytogenetic response rate at 6 months in patients with newly diagnosed Philadelphia chromosome-positive chronic phase chronic myelogenous leukemia treated with nilotinib.

Secondary

  • To establish the complete cytogenetic response rate at 3, 9, 12, 18, and 24 months in these patients.
  • To establish the molecular response rate at 3, 6, 9, 12, 18, and 24 months in these patients.
  • To establish the safety of this drug in these patients.
  • To correlate pharmacokinetic data with response rate and toxicity.
  • To correlate Bcr-Abl results using GeneXpert with Bcr-Abl results using international standardized quantitative PCR.
  • To estimate the prevalence of Bcr-Abl mutations prior to and during treatment.

OUTLINE: This is a multicenter study.

Patients receive oral nilotinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples are collected periodically for mutation analysis, Bcr-Abl analysis by quantitative PCR, metaphase cytogenetics, and pharmacokinetic analysis.

After completion of study therapy, patients are followed every 3 months for 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Cytogenetically confirmed chronic myelogenous leukemia (CML) by standard conventional cytogenetic analysis of bone marrow*

    • Newly diagnosed disease (within the past 6 months) NOTE: *FISH cannot be used
  • In chronic phase, as defined by the following:

    • Less than 15% blasts in peripheral blood and bone marrow
    • Less than 30% blasts plus promyelocytes in peripheral blood and bone marrow
    • Less than 20% basophils in peripheral blood
    • Platelet count ≥ 100,000/mm^3
    • No evidence of extramedullary leukemic involvement, except for hepatosplenomegaly
  • Philadelphia chromosome-positive disease as demonstrated by (9;22) translocation (presence of Bcr-Abl)

    • A review of ≥ 20 metaphases is required
  • No previously documented T315I mutations

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2.5 times ULN
  • Estimated glomerular filtration rate ≥ 30 mL/min
  • Serum amylase and lipase ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN (unless related to CML)
  • Potassium ≥ lower limit of normal (LLN)
  • Magnesium ≥ LLN
  • Phosphorous ≥ LLN
  • Total calcium ≥ LLN (corrected for serum albumin)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No impaired cardiac function including, but not limited to, any of the following:

    • LVEF < 45% or < LLN by ECHO
    • Inability to determine the QT interval on ECG
    • Complete left bundle branch block
    • Congenital 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/min)
    • QTc > 450 msec on an average of 3 serial baseline ECGs (using the QTcF formula)
    • Clinically documented myocardial infraction within the past 12 months
    • Unstable angina within the past 12 months
    • Other clinically significant heart disease (e.g., congestive heart failure or uncontrolled hypertension)
  • No severe or uncontrolled medical condition (e.g., uncontrolled diabetes or active or uncontrolled infection)
  • No history of significant congenital or acquired bleeding disorder unrelated to CML
  • No history of non-compliance to medical regimens
  • No other primary malignancy unless it is neither currently clinically significant nor requiring active intervention
  • No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
  • No acute pancreatitis within the past year
  • No history of chronic pancreatitis
  • No acute or chronic liver, pancreatic, or severe renal disease considered unrelated to CML

PRIOR CONCURRENT THERAPY:

  • No prior therapy for CML other than hydroxyurea and/or anagrelide
  • Prior imatinib mesylate allowed provided it was administered for ≤ 14 days
  • More than 30 days since prior and no other concurrent investigational agents
  • More than 4 weeks since prior major surgery and recovered
  • No other concurrent anticancer agents, including chemotherapy and biologic agents
  • No concurrent strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil)
  • No concurrent strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's wort)
  • No concurrent medications that have the potential to prolong QT interval
  • No concurrent grapefruit, star fruit, Seville oranges, or their derivatives
  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: NCT00809211

Locations
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Germany
Universitätsklinikum Charité Berlin
Berlin, Germany
Ireland
Belfast City Hospital
Belfast, Ireland
St. James's Hospital
Dublin, Ireland, 8
University College Hospital
Galway, Ireland
Israel
Chaim Sheba Medical Centre
Tel Hashomer, Israel
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: Mike O'Dwyer, MD University College London Hospitals
  More Information

Additional Information:
No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT00809211     History of Changes
Other Study ID Numbers: CDR0000629801, ICORG-08-02, EUDRACT-2008-004551-30, EU-20899
Study First Received: December 16, 2008
Last Updated: January 28, 2014
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
chronic myelogenous leukemia, BCR-ABL1 positive
chronic phase chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on September 16, 2014