Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response

Philadelphia Chromosome Positive Clinical Trial

— MACS0911  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01043874
• Other study ID #: CAMN107FJP01
• Status: Completed
• Phase: Phase 4
• First received: January 5, 2010
• Last updated: September 24, 2015
• Start date: December 2009
• Est. completion date: January 2014

Study information

• Verified date: September 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationJapan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: January 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myelogenous Leukemia in Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome
• Philadelphia Chromosome Positive

Intervention

Drug:
• Nilotinib
400 mg BID

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Gifu
Japan	Novartis Investigative Site	Hiroshima-city	Hiroshima
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Nagasaki-city	Nagasaki
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	OsakaSayama	Osaka
Japan	Novartis Investigative Site	Saga
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita-city	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	MMR is defined as BCR-ABL ratio (%) on IS = 0.1% (corresponds to = 3 log reduction of BCR-ABL transcripts from standardized baseline value	12 months after treatment	No
Secondary	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)	MMR is defined as BCR-ABL ratio (%) on IS = 0.1% (corresponds to = 3 log reduction of BCR-ABL transcripts from standardized baseline value	24 months after treatment	No
Secondary	Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .	MMR is defined as BCR-ABL ratio (%) on IS = 0.1% (corresponds to = 3 log reduction of BCR-ABL transcripts from standardized baseline value	month 24	No
Secondary	Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .	MMR is defined as BCR-ABL ratio (%) on IS = 0.1% (corresponds to = 3 log reduction of BCR-ABL transcripts from standardized baseline value	month 24	No