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Suboptimal Study Comparing Nilotinib and Imatinib
Link to the ClinicalTrials.gov recordInformation obtained from ClinicalTrials.gov on February 23, 2012
Title of trial/grant titleSuboptimal Study Comparing Nilotinib and Imatinib
Current status of trialRecruiting
Sponsors and collaboratorsNovartis Pharmaceuticals
Information provided byNovartis
ClinicalTrials.gov identifierNCT00802841
PurposeThere is no available data on the clinical benefit of dose escalation for patients with
suboptimal response to imatinib, and patients may still improve their response with
continuation of therapy at the standard dose as shown in the IRIS trial after 5 years of
follow-up. However, there is no data yet regarding the potential benefit of using nilotinib
in the group of patients with suboptimal response. In this study, the efficacy of nilotinib
400mg BID will be compared to imatinib 600mg QD.
Condition(s)Chronic Myelogenous Leukemia
Intervention(s)Drug: nilotinib
Drug: imatinib
PhasePhase III
Study type and designAllocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Official titleRandomized Phase Lll Study of Imatinib Dose Optimization Compared With Nilotinib in Patients With Chronic Myelogenous Leukemia and Suboptimal Response to Standard-dose Imatinib
Primary outcometo determine the comparative efficacy between imatinib dose escalation and nilotinib, in terms of CCyR) after 6 months of treatment, for patients with CML in chronic phase with suboptimal response to imatinib standard dose 6 months No
Secondary outcometo compare the rate of major molecular response (MMR) between 2 arms at 12 months 12 months No
to evaluate safety and tolerability of imatinib 600mg/daily and nilotinib 400mg twice a day 12 months Yes
to evaluate the rate of hematologic response in the two arms 12 months No
to evaluate the rate of CCyR at 12, 18 and 24 months on study and MMR at 18 and 24 months on study in the two treatment arms 12 months No
to investigate predictors of response to imatinib dose escalation among patients with CML in chronic phase with suboptimal response to 400mg imatinib 12 months Yes
Study startJune 2009
Minimum age18 Years
Maximum ageN/A
GenderBoth
Eligibility criteriaInclusion Criteria:

1. Male or female, aged â¿¥ 18 years;

2. ECOG Performance Status of 0, 1, or 2;

3. Diagnosis of Ph-positive CML in chronic phase (CP) at the start of therapy with
imatinib 400mg defined as follows:

- <15% blasts in peripheral blood and bone marrow;

- <30% blasts plus promyelocytes in peripheral blood and bone marrow;

- <20% basophils in the peripheral blood;

- â¿¥100x 109/L (â¿¥ 100,000/mm3) platelets;

- no evidence of extramedullary leukemia involvement, with the exception of
hepatosplenomegaly;

4. Patients with a suboptimal cytogenetic response to 400 mg of imatinib, defined as
follows (cytogenetic analysis to document suboptimal response must have been done
within 6 weeks of randomization):

- No cytogenetic response at â¿¥ 3 to <6 months (more than 95% Ph+ metaphases)

- No partial cytogenetic response at â¿¥ 6 to <12 months of treatment (36% to 95%
Ph+ metaphases on bone marrow); or

- No complete cytogenetic response at â¿¥ 12 to <18 months of treatment (1% to 35%
Ph+ metaphases on bone marrow);

Bone marrow karyotyping (BMK) is required on a minimum of 20 metaphases. Confirmation
of suboptimal response (SoR) by FISH is allowed if BMK is done outside the screening
window up to 4 weeks.

5. Patients receiving 400mg/daily imatinib standard dose for at least 3 months and no
more than 18 months;

6. No prior use of imatinib dose higher than 400 mg daily;

7. Previous use of IFN is allowed at a maximum of 90 days .There is no time limit if the
reason for switch from IFN to imatinib was intolerance.

8. Female patients of childbearing potential must have a negative urine pregnancy test
prior to randomization;

9. Adults must agree to use an acceptable method of contraception to avoid pregnancy for
the duration of the study and for 3 months after the end of study;

10. The following laboratory result must be present:

- Creatinine <2.0 X ULN

- Total bilirubin <1.5 X ULN (< 3.0 X ULN if related to disease);

- SGOT and SGPT < 2.5 X ULN (< 5.0 X ULN if related to disease);

- Serum lipase ⿤1.5 X ULN;

- Alkaline phosphatase ⿤2.5 X ULN (< 5.0 X ULN if related to disease)

- Serum potassium, phosphorus, magnesium and calcium â¿¥ LLN [lower limit of
normality] or correctable with supplements prior to first dose of study drug;
Written informed consent prior to any study procedures being performed

Exclusion Criteria:

1. Prior accelerated phase including clonal evolution or blast crisis CML;

2. Prior therapy with imatinib in combination with any other drug;

3. More than 18 months of imatinib therapy;

4. Patients who started imatinib therapy more than 12 months after the date of the
original diagnosis by bone marrow aspiration;

5. Patients receiving imatinib dose of 300 mg daily;

6. Previous treatment with any other tyrosine kinase inhibitor except Glivec

7. Patients with myelotoxicity â¿¥ Grade 2 at the time of randomization,

8. Previously documented T315I mutations;

9. Achieved prior PCyR or CCyR on imatinib therapy and lost that response before
entering the study;

10. Impaired cardiac function including one of the following:

11. Long QT syndrome or family history of long QT syndrome

12. Clinically significant resting brachycardia (<50 bpm)

13. QTcF >450 msec on screening ECG (using the QTcF formula). If QTc >450 and
electrolytes are not with normal ranges, electrolytes should be corrected and then
the patient rescreened for QTc to certify QTc <450 msec ;

14. Myocardial infarction within one year of the first dose of study drug;

15. Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, unstable angina, significant ventricular or atrial
tachyarrhythmias)

16. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drug;

17. Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment
cannot be either discontinued or switched to a different medication prior to starting
study drug;

18. 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;

19. History of previous acute pancreatitis within one year of study entry or medical
history of chronic pancreatitis;

20. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS
involvement, lumbar puncture is not required).

21. Women who are pregnant, breast feeding or of a childbearing potential without a
negative urine pregnancy test at screening. Male or female patients of childbearing
potential unwilling to use effective contraceptive precautions throughout the trial.
Post-menopausal women must be ammenorrheic for at least 12 months to be considered of
non-childbearing potential;

22. Patients with a history of another primary malignancy that is currently clinically
significant or currently requires active intervention;

23. Patients with any other clinically significant medical or surgical condition which,
according to investigators' discretion, should preclude participation;

24. Use of investigational agent within 28 days prior to enrollment in the study or
foreseen use of an investigational agent during the study;

25. Patients unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion criteria may apply
Overall contactNovartis Pharmaceuticals
tel: +1 800-340-6843
Study chairs or principal investigatorsNovartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals
LocationsArgentina

Novartis Investigative Site
Buenos Aires
Status: Recruiting

Argentina

Novartis Investigative Site
Buenos Aires
Status: Not yet recruiting

Brazil

Novartis Investigative Site
Belo Horizonte
Status: Recruiting

Brazil

Novartis Investigative Site
Botucatu
Status: Recruiting

Brazil

Novartis Investigative Site
Campinas
Status: Recruiting

Brazil

Novartis Investigative Site
Curitiba
Status: Recruiting

Brazil

Novartis Investigative Site
Fortaleza
Status: Recruiting

Brazil

Novartis Investigative Site
Jau
Status: Recruiting

Brazil

Novartis Investigative Site
Porto Alegre
Status: Recruiting

Brazil

Novartis Investigative Site
Porto Allegre
Status: Recruiting

Brazil

Novartis Investigative Site
Rio de Janeiro
Status: Recruiting

Brazil

Novartis Investigative Site
Sao Paulo
Status: Recruiting

Chile

Novartis Investigative Site
Santiago
Status: Not yet recruiting

China

Novartis Investigative Site
Beijing
Status: Not yet recruiting

China

Novartis Investigative Site
Nanjing
Status: Not yet recruiting

China

Novartis Investigative Site
Shanghai
Status: Not yet recruiting

China

Novartis Investigative Site
Suzhou
Status: Not yet recruiting

China

Novartis Investigative Site
Tianjin
Status: Not yet recruiting

China

Novartis Investigative Site
Zhejiang
Status: Not yet recruiting

Colombia

Novartis Investigative Site
Bucaramanga
Status: Recruiting

Costa Rica

Novartis Investigative Site
Cartago
Status: Not yet recruiting

Finland

Novartis Investigative Site
Helsinki
Status: Recruiting

Germany

Novartis Investigative Site
Berlin
Status: Recruiting

Guatemala

Novartis Investigative Site
Guatemala City
Status: Recruiting

India

Novartis Investigative Site
Chandigarh
Status: Not yet recruiting

India

Novartis Investigative Site
Mumbai
Status: Not yet recruiting

India

Novartis Investigative Site
New Delhi
Status: Not yet recruiting

India

Novartis Investigative Site
Vellore
Status: Not yet recruiting

Mexico

Novartis Investigative Site
Guadalajara
Status: Not yet recruiting

Mexico

Novartis Investigative Site
Mexico D.F.
Status: Recruiting

Mexico

Novartis Investigative Site
Monterrey
Status: Recruiting

Panama

Novartis Investigative Site
Panama City
Status: Recruiting

Peru

Novartis Investigative Site
Lima
Status: Recruiting

Poland

Novartis Investigative Site
Katowice
Status: Not yet recruiting

Poland

Novartis Investigative Site
Krakov
Status: Recruiting

Poland

Novartis Investigative Site
Wroclaw
Status: Not yet recruiting

Russian Federation

Novartis Investigative Site
Barnaul
Status: Recruiting

Russian Federation

Novartis Investigative Site
Ekaterinburg
Status: Recruiting

Russian Federation

Novartis Investigative Site
Krasnoyarsk
Status: Recruiting

Russian Federation

Novartis Investigative Site
Moscow
Status: Recruiting

Russian Federation

Novartis Investigative Site
Moscow region
Status: Not yet recruiting

Russian Federation

Novartis Investigative Site
Nizhny Novgorod
Status: Recruiting

Russian Federation

Novartis Investigative Site
Perm
Status: Recruiting

Russian Federation

Novartis Investigative Site
Rostov-on-Don
Status: Recruiting

Russian Federation

Novartis Investigative Site
Saint-Petersburg
Status: Not yet recruiting

Russian Federation

Novartis Investigative Site
Volgograd
Status: Recruiting

Venezuela

Novartis Investigative Site
Caracas
Status: Not yet recruiting

Venezuela

Novartis Investigative Site
Maracaibo
Status: Not yet recruiting
Study ID numbersCAMN107A2404
Last updatedSeptember 2, 2011
Record first receivedDecember 3, 2008
ClinicalTrials.gov identifierNCT00802841
Download dateInformation obtained from ClinicalTrials.gov on February 23, 2012
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