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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)

Phase 2
18 Years
Open (Enrolling)

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Trial Information

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)



- 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.


- 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

- 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.

Inclusion Criteria


- 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

- 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


- 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

- 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


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete cytogenetic response rate at 6 months as assessed by metaphase analysis

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Mike O'Dwyer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University College London Hospitals


Ireland: Irish Medicines Board

Study ID:




Start Date:

October 2008

Completion Date:

Related Keywords:

  • Leukemia
  • chronic myelogenous leukemia, BCR-ABL1 positive
  • chronic phase chronic myelogenous leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Philadelphia Chromosome



University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811