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

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

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.

Study Overview

• Status: Completed
• Conditions: Philadelphia Chromosome Positive; Chronic Myelogenous Leukemia in Chronic Phase
• Intervention / Treatment: Drug: Nilotinib

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • 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
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Novartis Investigative Site
    • Nagoya-city, Aichi, Japan, 466-8560
      • Novartis Investigative Site
    • Nagoya-city, Aichi, Japan, 453-8511
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
    • Kitakyushu, Fukuoka, Japan, 807-8556
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima-city, Hiroshima, Japan, 734-8551
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Miyagi
    • Sendai-city, Miyagi, Japan, 983-8520
      • Novartis Investigative Site
  • Nagasaki
    • Nagasaki-city, Nagasaki, Japan, 852-8501
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • 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
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib; 400 mg BID	Drug: Nilotinib; 400 mg BID; Other Names: AMN107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharma K.K., Novartis Pharma K.K.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: January 5, 2010
• First Submitted That Met QC Criteria: January 6, 2010
• First Posted (Estimate): January 7, 2010

Study Record Updates

• Last Update Posted (Estimate): April 8, 2016
• Last Update Submitted That Met QC Criteria: March 10, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Nilotinib; CML; Chronic myelogenous leukemia; CML-CP; Philadelphia chromosome positive; Chronic phase; Ph+; Suboptimal molecular response
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
• Other Study ID Numbers: CAMN107FJP01