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

Novartis Pharmaceuticals52 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Myelogenous Leukemia

Interventions

NilotinibDRUG

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).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

Highlands Oncology Group

Fayetteville, Arkansas, United States

Outcomes

Primary Outcomes

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).

Time frame: End of Cycles 1, 2, and 3

Secondary Outcomes

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

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

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

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.