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An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment (MACS0999)

Primary Purpose

Chronic Myelogenous Leukemia

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Nilotinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelogenous Leukemia focused on measuring CML, Leukemia, Tasigna, nilotinib, AMN107, CML-CP, Chronic Phase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patients ≥ 18 years of age
  2. Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
  3. Diagnosis of CML-CP associated with Bcr-Abl quantifiable by RQ-PCR (IS)
  4. 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
  5. CML-CP patients initiated on any dose of imatinib
  6. Ability to provide written informed consent prior to any study related screening procedures being done

Exclusion Criteria:

  1. Loss of CHR or cytogenetic response
  2. Prior accelerated phase or blast phase CML
  3. Previously documented T315I mutation
  4. Presence of chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
  5. Previous treatment with any other tyrosine kinase inhibitor except for imatinib.
  6. Treatment with other investigational agents within 30 days of Day 1.
  7. History of non-compliance to medical regimens or inability to grant consent.
  8. 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

Sites / Locations

  • Highlands Oncology Group
  • Hematology Oncology Services of Arkansas SC
  • USC Norris Cancer Center LAC & USC Medical Center
  • Southwest Cancer Care Murrieta
  • Rocky Mountain Cancer Centers RMCC - Aurora
  • Florida Cancer Institute
  • Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
  • Stroger Cook County Hospital John H. Stroger Hospital
  • St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn
  • St. Agnes Hospital
  • St. Louis University Cancer Center
  • Northwest Cancer Specialists Salmon Creek Office
  • Oregon Health Sciences University
  • The Jones Clinic
  • Texas Oncology, P.A.
  • Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
  • Texas Oncology Texas Oncology - Sugar Land
  • MD Anderson Cancer Center/University of Texas
  • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

nilotinib

Arm Description

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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 16, 2009
Last Updated
June 29, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00980018
Brief Title
An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
Acronym
MACS0999
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia
Keywords
CML, Leukemia, Tasigna, nilotinib, AMN107, CML-CP, Chronic Phase

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
nilotinib
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Other Intervention Name(s)
Tasigna, nilotinib, AMN107,
Intervention Description
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).
Primary Outcome Measure Information:
Title
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
Description
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).
Time Frame
End of Cycles 1, 2, and 3
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Complete Cytogenetic Response (CCyR) After Switching to Nilotinib for Participants Not Reporting CCyR at Baseline
Description
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
Time Frame
Cycles 1, 2, 6, 9, and 12
Title
Percentage of Participants Achieving Major Molecular Response (MMR) After the Switch in the Therapy for Participants Not Reporting MMR at Baseline
Description
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
Time Frame
Cycles 1,2,3,6,9,12
Title
Log Change in BCR-Abl Transcript Level From Baseline After the Switch Therapy
Description
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.
Time Frame
Cycles 1,2,3,6,9, and 12
Title
Duration of Complete Cytogenetic Response
Description
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.
Time Frame
18 months of follow up from the first documented response
Title
Time to Complete Cytogenetic Response in Participants Not Reporting at Baseline
Description
For time to CCyR, an event is defined as achievement of CCyR documented by bone marrow cytogenetics.
Time Frame
Cycle 12
Title
Duration of Major Molecular Response
Description
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.
Time Frame
18 months of follow up from the first documented response
Title
Time to Major Molecular Response (MMR) in Participants With MMR Absent at Baseline
Description
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.
Time Frame
Cycles 1,2,3,6,9,12
Title
Time to Optimal Imatinib-related Adverse Event Improvement
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Highlands Oncology Group
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Hematology Oncology Services of Arkansas SC
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
USC Norris Cancer Center LAC & USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Southwest Cancer Care Murrieta
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
Rocky Mountain Cancer Centers RMCC - Aurora
City
Greenwood Village
State/Province
Colorado
Country
United States
Facility Name
Florida Cancer Institute
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34655
Country
United States
Facility Name
Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
City
Ocoee
State/Province
Florida
ZIP/Postal Code
*see dep*
Country
United States
Facility Name
Stroger Cook County Hospital John H. Stroger Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
St. Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
St. Louis University Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Northwest Cancer Specialists Salmon Creek Office
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Jones Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Texas Oncology, P.A.
City
Bedford
State/Province
Texas
ZIP/Postal Code
76022
Country
United States
Facility Name
Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Texas Oncology Texas Oncology - Sugar Land
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
MD Anderson Cancer Center/University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77031
Country
United States
Facility Name
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Novartis Investigative Site
City
Brampton
State/Province
Ontario
ZIP/Postal Code
L6R 3J7
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
26993758
Citation
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.
Results Reference
derived
Links:
URL
http://NovartisClinicalTrials.com
Description
Related Info

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An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment

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