CMLPhase 4MACS1148NCT01131325
Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
A Phase 4 study testing nilotinib in people with CML and Philadelphia Chromosome Positive (Ph+), run by Novartis Pharmaceuticals at 3 sites in United States.
Trial summary
This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CML, Philadelphia Chromosome Positive (Ph+), Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels
- What is being tested?
- nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Oct 2010to 12 May 2011
- 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
- Cytogenetically confirmed Ph+ CML-CP Any prior dose of Imatinib
- Imatinib 400 mg daily for ≥7 consecutive days prior to imatinib trough collection
- Imatinib trough plasma concentration <850 ng/mL
Who cannot join
- Prior documented failure events as defined by ELN guidelines:
- Loss of CHR, CCyR, or clonal progression/Ph+
- Less than CHR at 3 months after diagnosis
- No CyR at 6 months after diagnosis
- Less than PCyR at 12 months after diagnosis
- Less than CCyR at 18 months after diagnosis
Show all 17Show fewer
- Prior accelerated phase or blast phase CML
- Previously documented T315I mutation
- Previous treatment for CML with any other tyrosine kinase inhibitor except for imatinib
- Patients who had any other treatment for CML (transplant) except interferon +/- ara- C, imatinib, hydroxyurea and/or anagrelide
- Impaired cardiac function
- Patients receiving therapy with strong inhibitors of CYP3A4 or medications that prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug.
- Any other malignancy that is clinically significant or requires active intervention.
- Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery
- Treatment with other investigational agents within 30 days of Day 1
- Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of nilotinib
- Sexually active male and female patients taking nilotinib unwilling to use adequate contraception throughout the trial and 3 months following discontinuation of study drug
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cancer Center of the High Plains
Amarillo, Texas, 79106
Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (2)
Dallas, Texas, 75246
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
Las Vegas, Nevada, 89109
About this study
Official title: A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations
This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.
- Conditions
- CML, Philadelphia Chromosome Positive (Ph+), Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels
- Being tested
- nilotinib
- Keywords
- Philadelphia chromosome positive, Ph+, chronic myelogenous leukemia chronic phase, CML-CP, low imatinib trough levels
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nilotinibDrug
Also called AMN107, Tasigna
All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | Not described Receives: Drug: nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Treatment Failure Events up to 2 Years
Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline.
Measured: up to 2 years
Secondary outcomes (6)
European LeukemiaNet (ELN)-Defined Optimal Responses
Measured: up to 2 years
Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib
Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit.
Major molecular response is defined as values equal or below 0.1% on the International Scale.
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
Measured: up to 2 years
Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib
Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/ complete response to the first documentation of the disease progression.
Measured: up to 2 years
Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years
Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.
Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria.
Overall survival time is defined as the time from the treatment start to the date of death due to any reason.
Measured: up to 2 years
European LeukemiaNet (ELN)-Defined Suboptimal Events
Measured: up to 2 years
Number of Participants Reported Adverse Events
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study start21 Oct 2010
- Primary completion12 May 2011
- Study completion12 May 2011
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.
- Other trials for CMLStudies 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01131325
- Sponsor's protocol ID
- CAMN107AUS20
- Acronym
- MACS1148
- Status last verified
- Oct 2020
- First submitted
- 25 May 2010
- Last updated
- 20 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations
- ClinicalTrials.gov ID
- NCT01131325
- Acronym / sponsor ID
- MACS1148 / CAMN107AUS20
- Conditions
- CML, Philadelphia Chromosome Positive (Ph+), Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels
- Keywords
- Philadelphia chromosome positive, Ph+, chronic myelogenous leukemia chronic phase, CML-CP, low imatinib trough levels
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Oct 2010 (actual)
- Primary completion
- 12 May 2011 (actual)
- Study completion
- 12 May 2011 (actual)
- First posted
- 26 May 2010 (estimated)
- Results
- Posted 20 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.
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: nilotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Cytogenetically confirmed Ph+ CML-CP Any prior dose of Imatinib
- Imatinib 400 mg daily for ≥7 consecutive days prior to imatinib trough collection
- Imatinib trough plasma concentration <850 ng/mL
Key exclusion criteria (17 listed)
- Prior documented failure events as defined by ELN guidelines:
- Loss of CHR, CCyR, or clonal progression/Ph+
- Less than CHR at 3 months after diagnosis
- No CyR at 6 months after diagnosis
- Less than PCyR at 12 months after diagnosis
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: AMN107, TasignaAll patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours | Drug | Nilotinib |
Primary outcome
Number of Treatment Failure Events up to 2 Years
Time frame: up to 2 years
Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline.
6 secondary outcomes
European LeukemiaNet (ELN)-Defined Optimal Responses
Time frame: up to 2 years
Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib
Time frame: up to 2 years
Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib
Time frame: up to 2 years
Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years
Time frame: up to 2 years
European LeukemiaNet (ELN)-Defined Suboptimal Events
Time frame: up to 2 years
Number of Participants Reported Adverse Events
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 Pharmaceuticals study director
Novartis Pharmaceuticals
3 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 CML and Philadelphia Chromosome Positive (Ph+), run by Novartis Pharmaceuticals at 3 sites in United States.
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 3 inclusion and 17 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: stopped early, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 20 May 2021). 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?
Number of Treatment Failure Events up to 2 Years (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2021.