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

Chronic Phase Chronic Myeloid Leukemia Clinical Trial

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 Imatinib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660906
• Other study ID #: CA180-400
• Secondary ID: 2011-006180-21
• Status: Completed
• Phase: Phase 4
• First received: August 7, 2012
• Last updated: November 17, 2016
• Start date: December 2012
• Est. completion date: October 2015

Study information

• Verified date: November 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with CML-CP patients achieving an optimal response to imatinib treatment with Grade 1 or 2 non-hematologic adverse events persisting for at least 2 months or recurring at least 3 times in the preceding 12 months, despite best supportive care

• Men and women with Chronic Myeloid Leukemia- Chronic Phase (CML-CP) Ph+ = age 18

• Daily Eastern Co-Operative Group (ECOG) performance status = 0 - 2

• Patient willing and able to give informed consent

• Life expectancy > 6 months

• Adequate renal function

• Adequate hepatic function

Exclusion Criteria:

• Patients who are pregnant or breast feeding

• Men whose partner is unwilling to avoid pregnancy.

• Previous treatment with any other tyrosine-kinase inhibitor (TKI), except for imatinib

• Current grade 3 or 4 imatinib related adverse event

• Prior documented T315I mutation

• Prior diagnosis of accelerated phase or blast crisis CML

• Previous loss of complete hematologic response (CHR) or major cytogenetic response (MCyR) on imatinib

• Concurrent medical condition of uncontrolled infection, cardiovascular diseases of cardiac failure, congenital long QT syndrome, ventricular arrhythmias, prolonged QT interval, second or third degree heart block, uncontrolled angina, myocardial infarction (MI) in the last 6 months, uncontrolled hypertension, pulmonary arterial hypertension, pleural or pericardial effusions, or history of bleeding disorder

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dasatinib
tablets, oral, 100 mg, Once daily, Up to12 months on study,

Locations

Country	Name	City	State
France	Local Institution	Creteil Cedex
France	Local Institution	Lille CEDEX
France	Local Institution	Pierre Benite cedex
France	Local Institution	Pringy Cedex
France	Local Institution	Vandoeuvre les Nancy
Germany	Local Institution	Jena
Germany	Local Institution	Koln
Germany	Local Institution	Lubeck
Germany	Local Institution	Mannheim
Germany	Local Institution	Rostock
Italy	Local Institution	Catania
Italy	Local Institution	Firenze
Italy	Local Institution	Napoli
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Italy	Local Institution	Torino
Korea, Republic of	Local Institution	Seoul
United States	Pacific Cancer Medical Center	Anaheim	California
United States	St. Agnes Healthcare, Inc.	Baltimore	Maryland
United States	The University Of Texas Md Anderson Cancer Center	Houston	Texas
United States	Cancer Center Of Central Connecticut	Southington	Connecticut
United States	Promedica Hematology & Oncology Assoicates	Sylvania	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With a Major Molecular Response (MMR) and MR 4.5 After Switching to Dasatinib	Molecular responses were assessed at 6 and 12 months after switching to dasatinib to determine if these baseline responses could be maintained. MR4.5, the number of treated participants with BCR-ABL transcripts = 0.0032% (IS) at 6 and 12 months from the date of dasatinib initiation; MMR, Major Molecular Response = 3-log reduction in BCR-ABL gene transcripts from a standardized baseline.	6 and 12 months	No
Primary	The Number of Imatinib-related Adverse Events (AEs) That Were Resolved, Improved, Remained Unchanged, or Worsened After 3 Months of Dasatinib Treatment	Dasatinib treatment was administered and its impact on the imatinib-related Grade 1/2 adverse events was assessed. 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. Resolved, AE no longer present or resolution of imatinib-related chronic Grade 1 or Grade 2 non-hematologic AEs. Improved, AE grade reduced from Grade 2 to Grade 1. Unchanged, AE did not improve or worsen or no change in grade. Worsened, grade Increased.	3 months after switch to dasatinib	Yes
Secondary	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	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.	Baseline to 3, 6, 12 months	No
Secondary	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	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.	Baseline to 6, 12 months	No
Secondary	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	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.	Date of first dose to 30 post last dose of study drug, an average of 3 years	Yes
Secondary	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	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.	3 months	Yes

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