Clinical Trial: Phase IV, Open-label, Multicenter Study of Dasatinib in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients With Chronic, Low-grade Non-Hematologic Toxicity to Imatinib

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase IV, Open-label, Multicenter Study of Dasatinib in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients With Chronic, Low-grade Non-Hematologic Toxicity to Imat

Brief Summary: This study proposes to evaluate the number of chronic, Grade 1 or 2, non-hematologic Adverse Events (AEs) that reduce in grade or resolve at 3 months after switching therapy from imatinib to dasatinib.

Detailed Summary:
Sponsor: Bristol-Myers Squibb

Current Primary Outcome: The Number of Imatinib-related Adverse Events (AEs) That Were Resolved, Improved, Remained Unchanged, or Worsened After 3 Months of Dasatinib Treatment [ Time Frame: 3 months after switch to dasatinib ]

Original Primary Outcome: Frequency of reduction in grade (Grade 2 to 1) or resolution of imatinib-related chronic Grade 1 or Grade 2 non-hematologic AEs at 3 months after switch to dasatinib [ Time Frame: 3 months after switch to dasatinib ]

Current Secondary Outcome:

• Mean Change From Baseline in Patient Reported CML Symptom Severity and Interference by MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Score After Switching to Dasatinib [ Time Frame: Baseline to 3, 6, 12 months ]
  The MD Anderson Symptom Inventory Chronic Myeloid Leukemia (MDASI-CML) is a validated questionnaire completed by study participants to assess symptom severity and symptom interference on daily function. These categories are divided into 5 domain summary scores: Core Symptom Severity Score, Interference Score, Symptom Severity Score, CML-Specific Symptom Severity Score, and 5 Most Severe Symptom Score. Scores were evaluated at baseline and after switching to Dasatinib on a range from 1 to 10; 1=not present/did not interfere, 10=as bad as you can imagine/interfered completely.
• Mean Change From Baseline in Patient Reported Quality of Life Measurements by The European Organization for Research and Treatment of Cancer - Quality of Life (QoL) Questionnaire (EORTC QLQ) Score After Switching to Dasatinib [ Time Frame: Baseline to 6, 12 months ]
  The EORTC QLQ-C30 questionnaire is completed by study participants to assess quality of life through nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social functioning); three symptom scales (fatigue, pain and nausea/vomiting); and a global health status/QoL scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures were evaluated at baseline and after switching to Dasatinib as an average raw score that was standardized by transformation, so that final scores were on a range in score from 0 to 100. A high score for a functional scale represents a healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale and single-item measures represents a high level of problematic symptomatology.
• Number of Participants With at Least 1 AE, Discontinuations Due to AE, Treatment-related AE, Serious Adverse Event (SAE), Treatment-related SAE, or Death as Outcome [ Time Frame: Date of first dose to 30 post last dose of study drug, an average of 3 years ]
  SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment-related=having certain, probable, possible, or missing relationship to study drug, dasatinib.
• The Percentage of Participants With at Least 1 Imatinib-related Grade 1 or Grade 2 Chronic Adverse Events (AEs) That Improved Without Worsening Within 3 Months of Switching to Dasatinib [ Time Frame: 3 months ]
  Dasatinib treatment was administered and its impact on the Imatinib-related Grade 1/2 adverse events was assessed. The percentage of participants is based on the number that had pre-existing Imatinib-related AEs. Measure assesses the participants with reduction or improvement of at least 1 Imatinib-related Grade 1 or Grade 2 chronic AE, without a worsening of any Imatinib-related, chronic adverse events after Dasatinib treatment. The severity of an adverse event is ranked based on grades that range from 1 to 4. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Potentially Life-threatening or disabling. Improved, AE grade reduced from Grade 2 to Grade 1. Worsened, Grade Increased. Confidence interval from Clopper-Pearson method.

Original Secondary Outcome:

• Change in patient reported CML symptom severity by Mean change in M.D. Anderson Symptom Inventory- Chronic Myeloid Leukemia (MDASI-CML) score [ Time Frame: 3, 6, 12 months ]
• Change in patient reported quality of life measured by EORTC-Quality of Life Questionnaire score [ Time Frame: 6, 12 months ]
• Frequency of dasatinib-related adverse events [ Time Frame: up to 12 months ]
• Proportion of patients with reduction or improvement of at least 1 imatinib-related Grade 1 or Grade 2 chronic AE, without a worsening of any imatinib-related, chronic adverse events [ Time Frame: 3 months ]
• Rate of major molecular response [ Time Frame: 6, 12 months ]

Dates:
Date Received: August 7, 2012
Date Started: December 2012
Date Completion:
Last Updated: November 17, 2016
Last Verified: November 2016