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

Chronic Myelogenous Leukemia Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00980018
• Other study ID #: CAMN107AUS17
• Status: Completed
• Phase: Phase 4
• Start date: December 2009
• Est. completion date: December 2012

Study information

• Verified date: June 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

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).

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
United States	St. Agnes Hospital	Baltimore	Maryland
United States	Texas Oncology, P.A.	Bedford	Texas
United States	St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn	Beech Grove	Indiana
United States	Stroger Cook County Hospital John H. Stroger Hospital	Chicago	Illinois
United States	Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp	Dallas	Texas
United States	Texas Oncology Texas Oncology - Sugar Land	Dallas	Texas
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	The Jones Clinic	Germantown	Tennessee
United States	Rocky Mountain Cancer Centers RMCC - Aurora	Greenwood Village	Colorado
United States	MD Anderson Cancer Center/University of Texas	Houston	Texas
United States	Hematology Oncology Services of Arkansas SC	Little Rock	Arkansas
United States	USC Norris Cancer Center LAC & USC Medical Center	Los Angeles	California
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4	Ocoee	Florida
United States	Northwest Cancer Specialists Salmon Creek Office	Portland	Oregon
United States	Oregon Health Sciences University	Portland	Oregon
United States	Southwest Cancer Care Murrieta	Poway	California
United States	St. Louis University Cancer Center	Saint Louis	Missouri
United States	Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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