Chronic Myelogenous LeukemiaPhase 4MACS0999NCT00980018
An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
A Phase 4 study testing Nilotinib in people with Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 23 sites in 2 countries.
Trial summary
The purpose of this exploratory study will be to examine changes in chronic low grade chronic adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE) grading, when patients are switched from imatinib to nilotinib therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous Leukemia
- What is being tested?
- Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 23 sitesin 2 countries
- Study dates
- Dec 2009to Dec 2012
- 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
- Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
- Diagnosis of CML-CP associated with Bcr-Abl quantifiable by RQ-PCR (IS)
- Patients must be an imatinib responder and achieved the following efficacy milestones as appropriate for the length of time on imatinib therapy as per protocol
- CML-CP patients initiated on any dose of imatinib
- Ability to provide written informed consent prior to any study related screening procedures being done
Who cannot join
- Loss of CHR or cytogenetic response
- Prior accelerated phase or blast phase CML
- Previously documented T315I mutation
- Presence of chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
- Previous treatment with any other tyrosine kinase inhibitor except for imatinib.
- Treatment with other investigational agents within 30 days of Day 1.
Show all 9Show fewer
- History of non-compliance to medical regimens or inability to grant consent.
- Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
23 sites in 2 countries.
23 sites in 2 countries
United States19 sites
St. Agnes Hospital
Baltimore, Maryland, 21229
Texas Oncology, P.A.
Bedford, Texas, 76022
St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn
Beech Grove, Indiana, 46107
Stroger Cook County Hospital John H. Stroger Hospital
Chicago, Illinois, 60612
Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
Dallas, Texas, 75231
Texas Oncology Texas Oncology - Sugar Land
Dallas, Texas, 75246
Highlands Oncology Group
Fayetteville, Arkansas, 72703
The Jones Clinic
Germantown, Tennessee, 38138
Rocky Mountain Cancer Centers RMCC - Aurora
Greenwood Village, Colorado
MD Anderson Cancer Center/University of Texas
Houston, Texas, 77031
Hematology Oncology Services of Arkansas SC
Little Rock, Arkansas, 72205
USC Norris Cancer Center LAC & USC Medical Center
Los Angeles, California, 90033
Florida Cancer Institute
New Port Richey, Florida, 34655
Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
Ocoee, Florida, *see dep*
Northwest Cancer Specialists Salmon Creek Office
Portland, Oregon, 97210
Oregon Health Sciences University
Portland, Oregon, 97239
Southwest Cancer Care Murrieta
Poway, California, 92064
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
San Antonio, Texas, 78229
St. Louis University Cancer Center
St Louis, Missouri, 63110
Canada4 sites
Novartis Investigative Site
Brampton, Ontario, L6R 3J7
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, H3A 1A1
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
About this study
Official title: An Exploratory Trial to Assess the Improvement of Chronic Low-grade Non-hematologic Adverse Events Experienced by Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Treated With Imatinib When Switched to Nilotinib Treatment
The purpose of this exploratory study will be to examine changes in chronic low grade chronic adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE) grading, when patients are switched from imatinib to nilotinib therapy.
- Conditions
- Chronic Myelogenous Leukemia
- Being tested
- Nilotinib
- Keywords
- CML, Leukemia, Tasigna, nilotinib, AMN107, CML-CP, Chronic Phase
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called Tasigna, nilotinib, AMN107,
Participants received two 150 [a total of 300 mg at each dosing] mg nilotinib capsules twice daily (bid) orally every morning and every evening approximately 12 hours apart and two 200 mg capsules [a total of 400 mg at each dosing] for patients enrolled prior to Protocol Amendment 1).
| Study group | Role | What they receive |
|---|---|---|
| nilotinib | Experimental | Participants received two 150 [a total of 300 mg at each dosing] mg nilotinib capsules twice daily (bid) orally every morning and every evening approximately 12 hours apart and two 200 mg capsules [a total of 400 mg at each dosing] for patients enrolled prior to Protocol Amendment 1). Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Improvement in Imatinib Related Chronic Low Grade Non Hematologic Adverse Event (AE) After Switch to Treatment With Nilotinib at End of Cycle 3
A patient was considered improved if 50% or more of the chronic imatinib-related chronic low grade nonhematologic AEs showed improvement (a decrease in CTCAE [Common Terminology Criteria for Adverse Events] grade or complete resolution).
Measured: End of Cycles 1, 2, and 3
Secondary outcomes (8)
Percentage of Participants Achieving Complete Cytogenetic Response (CCyR) After Switching to Nilotinib for Participants Not Reporting CCyR at Baseline
Time to complete cytogenetic response is defined as time from baseline to first time of CCyR as documented by bone marrow cytogenetics. Cytogenetic response was assessed as applicable by bone marrow cytogenetics 6, 12, and 18 months after starting imatinib therapy. Assess CCyR by bone marrow cytogenics
Measured: Cycles 1, 2, 6, 9, and 12
Percentage of Participants Achieving Major Molecular Response (MMR) After the Switch in the Therapy for Participants Not Reporting MMR at Baseline
Major Molecular Response (MMR) value at Molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized Interferon versus STI571 (IRIS) study or 0.1% per International Scale (IS). Time to MMR is defined as time from baseline to first time of MMR as documented by RQ-PCR
Measured: Cycles 1,2,3,6,9,12
Log Change in BCR-Abl Transcript Level From Baseline After the Switch Therapy
Levels of BCR-ABL transcripts were determined by quantitative RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR-ABL transcripts levels from the standardized baseline value will be calculated for each sample from the reported percent ratio of BCR-ABL transcripts versus control gene transcripts converted to a reference standard.
Measured: Cycles 1,2,3,6,9, and 12
Duration of Complete Cytogenetic Response
Duration of Complete Cytogenetic Response is defined as the time from first CCyR to first loss of CCyR as documented by bone marrow cytogenetics, or by FISH assay, whichever is earlier. The duration of CCyR begins on the day of enrollment for patients reporting CCyR at baseline.
Measured: 18 months of follow up from the first documented response
Time to Complete Cytogenetic Response in Participants Not Reporting at Baseline
For time to CCyR, an event is defined as achievement of CCyR documented by bone marrow cytogenetics.
Measured: Cycle 12
Duration of Major Molecular Response
Duration of Major Molecular Response is defined as the time from first MMR to first loss of MMR as documented by RQ-PCR. The duration of MMR begins on the day of enrollment for patients reporting MMR at baseline.
Measured: 18 months of follow up from the first documented response
Time to Major Molecular Response (MMR) in Participants With MMR Absent at Baseline
For time to MMR, an event is defined as achievement of MMR documented by RQ-PCR. Patients with MMR at the Screening RQ-PCR assay are counted as having time to MMR equal to 0.
Measured: Cycles 1,2,3,6,9,12
Time to Optimal Imatinib-related Adverse Event Improvement
Time to optimal improvement is defined as the time when the sum of the total CTCAE toxicity grades for a patient's chronic low-grade imatinib-related adverse events reaches its minimum value.
Measured: 18 months of follow up from the date of the first dose of study drug to the time to maximum decrease in CTCAE grade of these events
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2009 (estimated)
- Study startDec 2009
- Primary completionDec 2012
- Study completionDec 2012
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 Chronic Myelogenous LeukemiaStudies 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
- 52 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
- NCT00980018
- Sponsor's protocol ID
- CAMN107AUS17
- Acronym
- MACS0999
- Status last verified
- Jun 2021
- First submitted
- 16 Sep 2009
- Last updated
- 1 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cortes JE, Lipton JH, Miller CB, Busque L, Akard LP, Pinilla-Ibarz J, Keir C, Warsi G, Lin FP, Mauro MJ. Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study. Clin Lymphoma Myeloma Leuk. 2016 May;16(5):286-96. doi: 10.1016/j.clml.2016.02.002. Epub 2016 Feb 16.
PubMed 26993758
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Trial to Assess the Improvement of Chronic Low-grade Non-hematologic Adverse Events Experienced by Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Treated With Imatinib When Switched to Nilotinib Treatment
- ClinicalTrials.gov ID
- NCT00980018
- Acronym / sponsor ID
- MACS0999 / CAMN107AUS17
- Conditions
- Chronic Myelogenous Leukemia
- Keywords
- CML, Leukemia, Tasigna, nilotinib, AMN107, CML-CP, Chronic Phase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Sep 2009 (estimated)
- Results
- Posted 1 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this exploratory study will be to examine changes in chronic low grade chronic adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE) grading, when patients are switched from imatinib to nilotinib therapy.
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: NilotinibParticipants received two 150 [a total of 300 mg at each dosing] mg nilotinib capsules twice daily (bid) orally every morning and every evening approximately 12 hours apart and two 200 mg capsules [a total of 400 mg at each dosing] for patients enrolled prior to Protocol Amendment 1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female patients ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
- Diagnosis of CML-CP associated with Bcr-Abl quantifiable by RQ-PCR (IS)
- Patients must be an imatinib responder and achieved the following efficacy milestones as appropriate for the length of time on imatinib therapy as per protocol
- CML-CP patients initiated on any dose of imatinib
Key exclusion criteria (9 listed)
- Loss of CHR or cytogenetic response
- Prior accelerated phase or blast phase CML
- Previously documented T315I mutation
- Presence of chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
- Previous treatment with any other tyrosine kinase inhibitor except for imatinib.
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: Tasigna, nilotinib, AMN107,Participants received two 150 [a total of 300 mg at each dosing] mg nilotinib capsules twice daily (bid) orally every morning and every evening approximately 12 hours apart and two 200 mg capsules [a total of 400 mg at each dosing] for patients enrolled prior to Protocol Amendment 1). | Drug | nilotinib |
Primary outcome
Percentage of Participants With Improvement in Imatinib Related Chronic Low Grade Non Hematologic Adverse Event (AE) After Switch to Treatment With Nilotinib at End of Cycle 3
Time frame: End of Cycles 1, 2, and 3
A patient was considered improved if 50% or more of the chronic imatinib-related chronic low grade nonhematologic AEs showed improvement (a decrease in CTCAE [Common Terminology Criteria for Adverse Events] grade or complete resolution).
8 secondary outcomes
Percentage of Participants Achieving Complete Cytogenetic Response (CCyR) After Switching to Nilotinib for Participants Not Reporting CCyR at Baseline
Time frame: Cycles 1, 2, 6, 9, and 12
Percentage of Participants Achieving Major Molecular Response (MMR) After the Switch in the Therapy for Participants Not Reporting MMR at Baseline
Time frame: Cycles 1,2,3,6,9,12
Log Change in BCR-Abl Transcript Level From Baseline After the Switch Therapy
Time frame: Cycles 1,2,3,6,9, and 12
Duration of Complete Cytogenetic Response
Time frame: 18 months of follow up from the first documented response
Time to Complete Cytogenetic Response in Participants Not Reporting at Baseline
Time frame: Cycle 12
Duration of Major Molecular Response
Time frame: 18 months of follow up from the first documented response
Time to Major Molecular Response (MMR) in Participants With MMR Absent at Baseline
Time frame: Cycles 1,2,3,6,9,12
Time to Optimal Imatinib-related Adverse Event Improvement
Time frame: 18 months of follow up from the date of the first dose of study drug to the time to maximum decrease in CTCAE grade of these events
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26993758Cortes JE, Lipton JH, Miller CB, Busque L, Akard LP, Pinilla-Ibarz J, Keir C, Warsi G, Lin FP, Mauro MJ. Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study. Clin Lymphoma Myeloma Leuk. 2016 May;16(5):286-96. doi: 10.1016/j.clml.2016.02.002. Epub 2016 Feb 16.
- Related InfoLink provided by the sponsor.
Related trials for Chronic Myelogenous Leukemia
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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
23 sites in 2 countries: 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 Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 23 sites in 2 countries.
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 6 inclusion and 9 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 1 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Canada. 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 1 Jul 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?
Percentage of Participants With Improvement in Imatinib Related Chronic Low Grade Non Hematologic Adverse Event (AE) After Switch to Treatment With Nilotinib at End of Cycle 3 (time frame: End of Cycles 1, 2, and 3). 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 NCT00980018, 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 1 Jul 2021.