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

NCT ID: NCT01043874

Last Updated: 2016-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2014-01-31

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.

Conditions

Philadelphia Chromosome Positive; Chronic Myelogenous Leukemia in Chronic Phase

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

400 mg BID

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

400 mg BID

Interventions

Nilotinib

400 mg BID

Intervention Type: DRUG

Other Intervention Names

AMN107

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharma K.K.

Role: STUDY_DIRECTOR

Novartis Pharma K.K.

Locations

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Aomori, Aomori, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Kitakyushu, Fukuoka, Japan

Novartis Investigative Site

Gifu, Gifu, Japan

Novartis Investigative Site

Hiroshima, Hiroshima, Japan

Novartis Investigative Site

Kumamoto, Kumamoto, Japan

Novartis Investigative Site

Kyoto, Kyoto, Japan

Novartis Investigative Site

Sendai, Miyagi, Japan

Novartis Investigative Site

Nagasaki, Nagasaki, Japan

Novartis Investigative Site

Okayama, Okayama-ken, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Sayama, Osaka, Japan

Novartis Investigative Site

Suita, Osaka, Japan

Novartis Investigative Site

Saga, Saga-ken, Japan

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 27771544 (View on PubMed)

Other Identifiers

CAMN107FJP01

Identifier Type: -

Identifier Source: org_study_id