Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response (MACS0911)

• ClinicalTrials.gov Identifier: NCT01043874
• Recruitment Status: Completed
• First Posted: January 7, 2010
• Results First Posted: February 9, 2015
• Last Update Posted: April 8, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Philadelphia Chromosome Positive; Chronic Myelogenous Leukemia in Chronic Phase	Drug: Nilotinib	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: December 2009
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nilotinib; 400 mg BID	Drug: Nilotinib; 400 mg BID; Other Name: AMN107

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 12 months after treatment ]
   MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

Secondary Outcome Measures :

1. 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) [ Time Frame: 24 months after treatment ]
   MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value
2. Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) . [ Time Frame: month 24 ]
   MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value
3. Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) . [ Time Frame: month 24 ]
   MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Japan

Novartis Investigative Site

Nagoya-city, Aichi, Japan, 453-8511

Novartis Investigative Site

Nagoya-city, Aichi, Japan, 466-8560

Novartis Investigative Site

Nagoya, Aichi, Japan, 464-8681

Novartis Investigative Site

Fukuoka-city, Fukuoka, Japan, 812-8582

Novartis Investigative Site

Kitakyushu, Fukuoka, Japan, 807-8556

Novartis Investigative Site

Hiroshima-city, Hiroshima, Japan, 734-8551

Novartis Investigative Site

Kumamoto City, Kumamoto, Japan, 860-8556

Novartis Investigative Site

Sendai-city, Miyagi, Japan, 983-8520

Novartis Investigative Site

Nagasaki-city, Nagasaki, Japan, 852-8501

Novartis Investigative Site

Okayama-city, Okayama, Japan, 700-8558

Novartis Investigative Site

Osaka-city, Osaka, Japan, 545-8586

Novartis Investigative Site

OsakaSayama, Osaka, Japan, 589-8511

Novartis Investigative Site

Suita-city, Osaka, Japan, 565-0871

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan, 113-8519

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan, 113-8655

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan, 160-0023

Novartis Investigative Site

Aomori, Japan, 030-8553

Novartis Investigative Site

Gifu, Japan, 501-1194

Novartis Investigative Site

Kyoto, Japan, 602-8566

Novartis Investigative Site

Saga, Japan, 849-8501

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharma K.K.; Novartis Pharma K.K.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01043874
• Other Study ID Numbers: CAMN107FJP01
• First Posted: January 7, 2010
• Results First Posted: February 9, 2015
• Last Update Posted: April 8, 2016
• Last Verified: March 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Chronic phase; Chronic myelogenous leukemia; CML; Philadelphia chromosome positive; Ph+; Nilotinib; CML-CP; Suboptimal molecular response

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes