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CompletedNCT01043874MACS0911Updated Apr 8, 2016Results posted

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

A Phase 4 interventional study of Nilotinib in Philadelphia Chromosome Positive and Chronic Myelogenous Leukemia in Chronic Phase, sponsored by Novartis Pharmaceuticals. Completed at 20 sites in Japan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-04-08.

Sponsored by Novartis Pharmaceuticals · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
45
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • 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
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 45 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Nilotinib

    400 mg BID

    Drug: Nilotinib

Interventions

  • DrugNilotinib

    400 mg BID

    Also known as: AMN107

06

What researchers measure

Primary outcomes

  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.

    MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

    Time frame: 12 months after treatment

Secondary outcomes

  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)

    MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

    Time frame: 24 months after treatment

  2. 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

    Time frame: month 24

  3. 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

    Time frame: month 24

07

Results

Posted Feb 9, 2015

Participant flow

Participant flow — Overall Study
MilestoneNilotinib
Started45
Completed39
Not completed6
Withdrew: Adverse event3
Withdrew: Withdrawal by subject1
Withdrew: Lack of efficacy1
Withdrew: Administrative problems1

Outcome measures

PrimaryMMR 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

Time frame:
12 months after treatment
Reported as:
Number · % participants achieving MMR
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.
% participants achieving MMRNilotinib
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.51.1 (35.8 to 66.3)
SecondaryMMR 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

Time frame:
24 months after treatment
Reported as:
Number · % participants achieving MMR
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)
% participants achieving MMRNilotinib
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)66.7 (51.0 to 80.0)
SecondaryTime 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

Time frame:
month 24
Reported as:
Mean · months
Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .
monthsNilotinib
Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .5.19 ± 5.494
SecondaryDuration 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

Time frame:
month 24
Reported as:
Number · % participants w/ durable MMR at 24 mos
Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .
% participants w/ durable MMR at 24 mosNilotinib
Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .51.1 (35.8 to 66.3)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Nilotinib—7/45 (15.6%)45/45 (100%)
Most frequent serious events
Most frequent serious events
EventNilotinib
AnaemiaBlood and lymphatic system disorders1/45
Bile duct stoneHepatobiliary disorders1/45
PneumoniaInfections and infestations1/45
DehydrationMetabolism and nutrition disorders1/45
Chronic myeloid leukaemia transformationNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/45
Malignant neoplasm of renal pelvisNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/45
Erythema multiformeSkin and subcutaneous tissue disorders1/45
Most frequent other events
Showing 10 of 41
Most frequent other events
EventNilotinib
HyperbilirubinaemiaHepatobiliary disorders24/45
NasopharyngitisInfections and infestations21/45
HeadacheNervous system disorders17/45
RashSkin and subcutaneous tissue disorders15/45
Alanine aminotransferase increasedInvestigations14/45
HypophosphataemiaMetabolism and nutrition disorders13/45
Lipase increasedInvestigations11/45
ConstipationGastrointestinal disorders10/45
NauseaGastrointestinal disorders9/45
MyalgiaMusculoskeletal and connective tissue disorders9/45

Baseline characteristics

Age, Continuous
Age, Continuous(years)Nilotinib
Mean49.5 ± 14.89
Sex: Female, Male
Sex: Female, Male(Participants)Nilotinib
Female16
Male29
08

Study locations

20 sites
  • Novartis Investigative Site
    Nagoya-city, Aichi 453-8511, Japan
  • Novartis Investigative Site
    Nagoya-city, Aichi 466-8560, Japan
  • Novartis Investigative Site
    Nagoya, Aichi 464-8681, Japan
  • Novartis Investigative Site
    Fukuoka-city, Fukuoka 812-8582, Japan
  • Novartis Investigative Site
    Kitakyushu, Fukuoka 807-8556, Japan
  • Novartis Investigative Site
    Hiroshima-city, Hiroshima 734-8551, Japan
  • Novartis Investigative Site
    Kumamoto City, Kumamoto 860-8556, Japan
  • Novartis Investigative Site
    Sendai-city, Miyagi 983-8520, Japan
  • Novartis Investigative Site
    Nagasaki-city, Nagasaki 852-8501, Japan
  • Novartis Investigative Site
    Okayama-city, Okayama 700-8558, Japan
  • Novartis Investigative Site
    Osaka-city, Osaka 545-8586, Japan
  • Novartis Investigative Site
    OsakaSayama, Osaka 589-8511, Japan
  • Novartis Investigative Site
    Suita-city, Osaka 565-0871, Japan
  • Novartis Investigative Site
    Bunkyo-ku, Tokyo 113-8519, Japan
  • Novartis Investigative Site
    Bunkyo-ku, Tokyo 113-8655, Japan
  • Novartis Investigative Site
    Shinjuku-ku, Tokyo 160-0023, Japan
  • Novartis Investigative Site
    Aomori, 030-8553, Japan
  • Novartis Investigative Site
    Gifu, 501-1194, Japan
  • Novartis Investigative Site
    Kyoto, 602-8566, Japan
  • Novartis Investigative Site
    Saga, 849-8501, Japan
09

References and documents

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. PubMed 27771544 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 8, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01043874
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Jan 7, 2010
Start date
Dec 2009
Primary completion
Dec 2013
Completion
Jan 2014
Results posted
Feb 9, 2015
Last update
Apr 8, 2016

Study contacts

Novartis Pharma K.K.
study director · Novartis Pharma K.K.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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