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Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.

Phase 2
18 Years
Open (Enrolling)

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Trial Information

Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.



- To assess the complete cytogenetic response rate at 12 months in patients with
Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous
leukemia treated with nilotinib and imatinib mesylate.


- To assess the complete cytogenetic response rate at 6 and 24 months in these patients.

- To assess the major and complete molecular response rate at 6, 12, and 24 months in
these patients.

- To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months
during and for 3 years after study treatment.

- To assess the rate of failures and the time to failure at 12, 24, and 60 months in
these patients.

- To assess compliance, toxicity, and adverse events in these patients.

- To understand the relationship between response, gene expression profile, biomarkers,
and drug plasma concentrations in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral nilotinib twice daily in months 1-3, 7-9, 13-15, and 19-21 and oral
imatinib mesylate once daily in months 4-6, 10-12, 16-18, and 22-24. Treatment continues for
24 months in the absence of disease progression or unacceptable toxicity. Patients may be
eligible to continue oral nilotinib and oral imatinib mesylate for up to another 36 months
if it is in the interest of the patient.

Blood samples and bone marrow biopsies are collected periodically for cytogenetic response
by chromosome banding analysis and FISH analysis; real-time quantitative PCR mutational
analysis and single nucleotide polymorphism analysis of BCR-ABL transcripts; and gene
expression profiling and correlative biomarker studies.

After completion of study therapy, patients are followed every 6 months for 3 years and then
every 12 months for 5 years.

Inclusion Criteria


- Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the
following criteria:

- Early chronic phase disease (< 6 months from diagnosis)

- Philadelphia chromosome-positive disease

- BCR-ABL-positive


- WHO performance status 0-1

- ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due
to leukemia)

- Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia)

- Serum bilirubin = 1.5 times ULN

- Serum creatinine = 1.5 times ULN

- Serum amylase = 1.5 times ULN

- Serum lipase = 1.5 times ULN

- Normal serum levels of the following or correctable with supplements:

- Potassium

- Total calcium (corrected for serum albumin)

- Magnesium

- Phosphorus

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier method contraception during study and for
up to 3 months following completion of study treatment

- No impaired cardiac function, including any of the following:

- LVEF < 45% by MUGA scan or echocardiogram

- Uncontrolled congestive heart failure

- Uncontrolled hypertension

- Uncontrolled angina pectoris

- Myocardial infarction within the past 12 months

- No significant electric heart abnormalities, including any of the following:

- History or active ventricular or atrial tachyarrhythmias

- Congenital long QT syndrome and/or QTc > 450 msec on screening ECG

- No history of acute (within one year) or chronic pancreatitis

- No impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

- No acute or chronic liver or renal disease considered unrelated to leukemia

- No known diagnosis of HIV infection

- No other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes, active or uncontrolled infection) that could cause unacceptable safety
risks or compromise compliance with the protocol

- No other primary malignancy that is currently clinically significant or requires
active intervention


- More than 2 weeks since prior major surgery and recovered

- More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days

- More than 4 weeks since prior investigational drug

- No prior hematopoietic stem cell transplantation

- No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol,

- No concurrent medications that would prolong the QT interval

- No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy

- Prior treatment with hydroxyurea or anagrelide allowed

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

Outcome Time Frame:

At 12 months from study entry

Safety Issue:


Principal Investigator

Michele Baccarani, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gruppo Italiano Malattie EMatologiche dell'Adulto


Italy: Ethics Committee

Study ID:




Start Date:

February 2009

Completion Date:

August 2014

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