Philadelphia Chromosome PositivePhase 4MACS0911NCT01043874
Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response
A Phase 4 study testing Nilotinib in people with Philadelphia Chromosome Positive and Chronic Myelogenous Leukemia in Chronic Phase, run by Novartis Pharmaceuticals at 20 sites in Japan.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Philadelphia Chromosome Positive, Chronic Myelogenous Leukemia in Chronic Phase
- What is being tested?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 20 sitesJapan
- Study dates
- Dec 2009to Jan 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years of age.
- ECOG 0, 1, or 2.
- Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.
- 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:
- Patients who have achieved CCyR (0% Ph+ chromosomes).
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- 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.
- Patients who meet the following laboratory tests criteria:
- total bilirubin < 1.5 x ULN,
- SGOT and SGPT < 2.5 x ULN,
- creatinine < 1.5 x ULN,
- Serum amylase and lipase ≤ 1.5 x ULN,
- Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
- Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with supplements prior to the first dose of study drug.
- Written informed consent prior to any study related screening procedures being performed.
Who cannot join
- Prior accelerated phase or blast crisis CML.
- Previously documented T315I mutations.
- Presence of chromosomal abnormalities other than Ph+.
- Previous treatment with any other tyrosine kinase inhibitor except imatinib.
- Impaired cardiac function including any one of the following:
- Complete left bundle branch block
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- Congenital long QT syndrome or family history of long QT syndrome
- History of or presence of significant ventricular or atrial tachyarrhythmias
- Clinically significant resting brachycardia (<50 bpm)
- QTcF > 450 msec on screening ECG
- Use of a ventricular-paced pacemaker
- Myocardial infarction during the last 12 months
- Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina).
- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Japan20 sites
Novartis Investigative Site
Aomori, Aomori, 030-8553
Novartis Investigative Site
Bunkyo-ku, Tokyo, 113-8519
Novartis Investigative Site
Bunkyo-ku, Tokyo, 113-8655
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Gifu, Gifu, 501-1194
Novartis Investigative Site
Hiroshima, Hiroshima, 734-8551
Novartis Investigative Site
Kitakyushu, Fukuoka, 807-8556
Novartis Investigative Site
Kumamoto, Kumamoto, 860-8556
Novartis Investigative Site
Kyoto, Kyoto, 602-8566
Novartis Investigative Site
Nagasaki, Nagasaki, 852-8501
Novartis Investigative Site
Nagoya, Aichi-ken, 453-8511
Novartis Investigative Site
Nagoya, Aichi-ken, 464-8681
Novartis Investigative Site
Nagoya, Aichi-ken, 466-8560
Novartis Investigative Site
Okayama, Okayama-ken, 700-8558
Novartis Investigative Site
Osaka, Osaka, 545-8586
Novartis Investigative Site
Saga, Saga-ken, 849-8501
Novartis Investigative Site
Sayama, Osaka, 589-8511
Novartis Investigative Site
Sendai, Miyagi, 983-8520
Novartis Investigative Site
Shinjuku-ku, Tokyo, 160-0023
Novartis Investigative Site
Suita, Osaka, 565-0871
About this study
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
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.
- Being tested
- Nilotinib
- Keywords
- Chronic phase, Chronic myelogenous leukemia, CML, Philadelphia chromosome positive, Ph+, Nilotinib, CML-CP, Suboptimal molecular response
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called AMN107
400 mg BID
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | 400 mg BID Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months after treatment
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2010 (estimated)
- Study startDec 2009
- Primary completionDec 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Philadelphia Chromosome PositiveStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharma K.K., Study director, Novartis Pharma K.K.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01043874
- Sponsor's protocol ID
- CAMN107FJP01
- Acronym
- MACS0911
- Status last verified
- Mar 2016
- First submitted
- 5 Jan 2010
- Last updated
- 8 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01043874
- Acronym / sponsor ID
- MACS0911 / CAMN107FJP01
- Keywords
- Chronic phase, Chronic myelogenous leukemia, CML, Philadelphia chromosome positive, Ph+, Nilotinib, CML-CP, Suboptimal molecular response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 7 Jan 2010 (estimated)
- Results
- Posted 9 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: Nilotinib400 mg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female patients ≥ 18 years of age.
- ECOG 0, 1, or 2.
- Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.
- Patients with suboptimal molecular response to imatinib treatment continued for at least 18 months (first line therapy)
- Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to study entry.
Key exclusion criteria (14 listed)
- Prior accelerated phase or blast crisis CML.
- Previously documented T315I mutations.
- Presence of chromosomal abnormalities other than Ph+.
- Previous treatment with any other tyrosine kinase inhibitor except imatinib.
- Impaired cardiac function including any one of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibAlso: AMN107400 mg BID | Drug | Nilotinib |
Primary outcome
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
3 secondary outcomes
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
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
Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .
Time frame: month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27771544Miyamura 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharma K.K. study director
Novartis Pharma K.K.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nilotinib in people with Philadelphia Chromosome Positive and Chronic Myelogenous Leukemia in Chronic Phase, run by Novartis Pharmaceuticals at 20 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01043874, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2016.