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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: Nilotinib

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 1A1
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Little Rock, Arkansas, United States, 72205
      • Hematology Oncology Services of Arkansas SC
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center LAC & USC Medical Center
    • Poway, California, United States, 92064
      • Southwest Cancer Care Murrieta
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC - Aurora
  • Florida
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Institute
    • Ocoee, Florida, United States, *see dep*
      • Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Stroger Cook County Hospital John H. Stroger Hospital
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Salmon Creek Office
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology, P.A.
    • Dallas, Texas, United States, 75231
      • Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
    • Dallas, Texas, United States, 75246
      • Texas Oncology Texas Oncology - Sugar Land
    • Houston, Texas, United States, 77031
      • MD Anderson Cancer Center/University of Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nilotinib; 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; 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).; Other Names: Tasigna, nilotinib, AMN107,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	End of Cycles 1, 2, and 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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.	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.	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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimate): September 18, 2009

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Leukemia; CML; CML-CP; Chronic Phase; Tasigna; nilotinib; AMN107
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: CAMN107AUS17