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A Phase II, Non Randomized, Open Label, Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

Phase 4
18 Years
Not Enrolling
Chronic Myeloid Leukemia (CML)

Thank you

Trial Information

A Phase II, Non Randomized, Open Label, Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

Patients will be evaluated for safety throughout the study and for response every month for
the first 3 months, then every 3 months thereafter up to month 24.

BCR-ABL transcripts measurement by QRT-PCR and mutation analyses will be done on peripheral
blood samples and cytogenetic analyses on bone marrow aspirates.

Laboratory tests (hematology, blood chemistry), ECG and physical examination will be done on
every visit.

Drug pharmacokinetics will be assessed in this study. For the screening Baseline periods,
see chart attached

Inclusion Criteria:

- Male or female patients age > 18 years old;

- Diagnosis of Chronic Myeloid leukemia in Accelerated Phase (CML-AP);

- Patients with CML-AP(See Appendix 1) within 3 months of diagnosis (date of initial
diagnosis is the date of first reported cytogenetic analysis). Standard conventional
cytogenetic analysis must be done on bone marrow. FISH cannot be used for purpose of

- Patients with atypical BCR-ABL transcripts are eligible (transcripts other then b2a2
an b3a2);

- No previous treatment with any antileukemic drugs with the exception of hydroxyurea
(HU) and/or anagrelide. 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;

- ECOG 0,1 or 2;

- Normal serum levels > LLN (lower limit of normal) or corrected to within normal
limits with supplements, prior to the first dose of study medication, of potassium
magnesium and calcium;

- AST and ALT < 2.5 x ULN (upper limit of normal) or < 5.0 x ULN if considered due to

- Alkaline phosphatase < 2.5 x ULN, unless considered due to leukemia;

- Total bilirubin < 1.5 x ULN;

- Serum lipase and amylase < 1.5 x ULN;

- Written informed consent prior to any study procedures being performed.

Exclusion Criteria:

- Patients in Chronic and Blastic Phases.

- Patients who are considered Ph negative because they do not have a confirmed
cytogenetic diagnosis of Philadelphia Ph+ chromosome (9;22 translocation) in > 20

- Treatment with tyrosine kinase inhibitors or other antileukemic agents or treatments
(including HSCT) for longer than 2 weeks, with the exception of HU and/or anagrelide

- Previously documented T315I mutations;

- Uncontrolled congestive heart failure or hypertension;

- Myocardial infarction or unstable angina pectoris within past 12 months;

- Significant arrhythmias, including history or presence of clinically significant
ventricular or atrial tachyarrhythmias, clinically significant bradycardias, long QT
syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula). Patients
with complete LBBB;

- History of confirmed acute or chronic pancreatitis;

- Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active
or uncontrolled infections, acute or chronic liver and renal disease) that could
cause unacceptable safety risks or compromise compliance with the protocol;

- Impaired gastrointestinal function or GI 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 bypass surgery);

- Patients with another primary malignancy that is currently clinically significant or
requires active intervention;

- Concomitant medications with potential QT prolongation (See link for complete list:;

- Concomitant medications known to interact with CYP450 isoenzymes (CYP 3A4, CYP2C9,
CYP2C8, (See link for complete list (;

- History of significant congenital or acquired bleeding disorder unrelated to cancer;

- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy;

- Patients who are pregnant or breastfeeding or adults of reproductive potential not
employing an effective method of birth control. (Women of childbearing potential must
have a negative serum pregnancy test within 48 hrs prior to administration of
nilotinib). Postmenopausal women must be amenorrheic for at least 12 months to be
considered of non-childbearing potential. Male and female patients must agree to
employ an effective barrier method of birth control throughout the entire study and
up to 3 months following discontinuation of study drug;

- Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF,
GM-CSF) 1 week prior to starting study drug;

- Treatment with other investigational agents (defined as not used in accordance with
the approved indication) within 30 days of Day 1;

- Patients unwilling or unable to comply with the protocol.


Patients who did not meet one or more inclusion or exclusion criteria may be re-screened
for this study at a later time if the medical condition is transient and has been
appropriately treated (provided they enter the study within 3 months of diagnosis). Date
of diagnosis is defined as date of confirmatory bone marrow cytogenetic analysis.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the safety and tolerability profile of nilotinib in newly diagnosed CML-AP

Outcome Description:

The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.

Outcome Time Frame:

12 month

Safety Issue:


Principal Investigator

Novartis Biociências SA - Brazil

Investigator Role:

Study Director

Investigator Affiliation:



Brazil: National Health Surveillance Agency

Study ID:




Start Date:

January 2013

Completion Date:

October 2016

Related Keywords:

  • Chronic Myeloid Leukemia (CML)
  • Nilotinib
  • CML patients
  • accelerated phase
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive