Clinical trial NCT01043874: Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response
Official title: A Phase IV Study of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have Suboptimal Molecular Response on Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Philadelphia Chromosome Positive
Chronic Myelogenous Leukemia in Chronic Phase
Keywords: Chronic phase
Chronic myelogenous leukemia
CML
Philadelphia chromosome positive
Ph+
Nilotinib
CML-CP
Suboptimal molecular response
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-01-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the major molecular response (MMR) rate at 12 months of nilotinib treatment on study in patients with Philadelphia Chromosome Positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have a suboptimal molecular response to imatinib at 18 months or later.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.
2. ECOG 0, 1, or 2.
3. Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.
4. Patients with suboptimal molecular response to imatinib treatment continued for at least 18 months (first line therapy)

   Suboptimal molecular response defined as all of the following conditions:
   1. Patients who have achieved CCyR (0% Ph+ chromosomes).
   2. Patients who don't achieve MMR (MMR defined as BCR-ABL/ABL ratio of ≤ 0.1% on the International Scale as detected by RQ-PCR).

   The treatment with imatinib defined as:

   Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to study entry.
5. Patients who meet the following laboratory tests criteria:

   1. total bilirubin \< 1.5 x ULN,
   2. SGOT and SGPT \< 2.5 x ULN,
   3. creatinine \< 1.5 x ULN,
   4. Serum amylase and lipase ≤ 1.5 x ULN,
   5. Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
   6. Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with supplements prior to the first dose of study drug.
6. Written informed consent prior to any study related screening procedures being performed.

Exclusion Criteria:

1. Prior accelerated phase or blast crisis CML.
2. Previously documented T315I mutations.
3. Presence of chromosomal abnormalities other than Ph+.
4. Previous treatment with any other tyrosine kinase inhibitor except imatinib.
5. Impaired cardiac function including any one of the following:

   1. Complete left bundle branch block
   2. Congenital long QT syndrome or family history of long QT syndrome
   3. History of or presence of significant ventricular or atrial tachyarrhythmias
   4. Clinically significant resting brachycardia (\<50 bpm)
   5. QTcF \> 450 msec on screening ECG
   6. Use of a ventricular-paced pacemaker
   7. Myocardial infarction during the last 12 months
   8. Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina).
6. Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St John's Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See Section 6.4.3 for complete list of these medications.

Primary outcomes:
measure: MMR Rate at 12 Mos. of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Molecular Response to Imatinib at 18 Months or Later.
timeFrame: 12 months after treatment
Secondary outcomes:
measure: MMR Rate at 24 Months of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
timeFrame: 24 months after treatment
measure: Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .
timeFrame: month 24
measure: Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .
timeFrame: month 24
Other outcomes:
Locations:
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Hiroshima-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Nagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Aomori
country: Japan
facility: Novartis Investigative Site
city: Gifu
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Saga
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharma K.K.
name: Novartis Pharma K.K.
role: STUDY_DIRECTOR
References:
citation: Miyamura K, Miyamoto T, Tanimoto M, Yamamoto K, Kimura S, Kawaguchi T, Matsumura I, Hata T, Tsurumi H, Saito S, Hino M, Tadokoro S, Meguro K, Hyodo H, Yamamoto M, Kubo K, Tsukada J, Kondo M, Aoki M, Okada H, Yanada M, Ohyashiki K, Taniwaki M. Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy. Leuk Res. 2016 Dec;51:11-18. doi: 10.1016/j.leukres.2016.09.009. Epub 2016 Sep 5.