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

• ClinicalTrials.gov Identifier: NCT01660906
• Recruitment Status: Completed
• First Posted: August 9, 2012
• Results First Posted: November 22, 2016
• Last Update Posted: November 22, 2016
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Phase Chronic Myeloid Leukemia	Drug: Dasatinib	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: December 2012
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dasatinib (100 mg)	Drug: Dasatinib; tablets, oral, 100 mg, Once daily, Up to12 months on study,; Other Name: Sprycel

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.

Other Outcome Measures:

1. Number of Participants With a Major Molecular Response (MMR) and MR 4.5 After Switching to Dasatinib [ Time Frame: 6 and 12 months ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Pacific Cancer Medical Center

Anaheim, California, United States, 92801

United States, Connecticut

Cancer Center Of Central Connecticut

Southington, Connecticut, United States, 06489

United States, Maryland

St. Agnes Healthcare, Inc.

Baltimore, Maryland, United States, 21229

United States, Ohio

Promedica Hematology & Oncology Assoicates

Sylvania, Ohio, United States, 43560

United States, Texas

The University Of Texas Md Anderson Cancer Center

Houston, Texas, United States, 77030

France

Local Institution

Creteil Cedex, France, 94010

Local Institution

Lille CEDEX, France, 59037

Local Institution

Pierre Benite cedex, France, 69495

Local Institution

Pringy Cedex, France, 74374

Local Institution

Vandoeuvre les Nancy, France, 54511

Germany

Local Institution

Jena, Germany, 07747

Local Institution

Koln, Germany, 50937

Local Institution

Lubeck, Germany, 23562

Local Institution

Mannheim, Germany, 68169

Local Institution

Rostock, Germany, 18055

Italy

Local Institution

Catania, Italy, 95124

Local Institution

Firenze, Italy, 50134

Local Institution

Napoli, Italy, 80131

Local Institution

Roma, Italy, 00144

Local Institution

Roma, Italy, 00161

Local Institution

Torino, Italy, 10126

Korea, Republic of

Local Institution

Seoul, Korea, Republic of, 137-701

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

Additional Information:

BMS clinical trial educational resource 

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01660906
• Other Study ID Numbers: CA180-400; 2011-006180-21 ( EudraCT Number )
• First Posted: August 9, 2012
• Results First Posted: November 22, 2016
• Last Update Posted: November 22, 2016
• Last Verified: November 2016

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Dasatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action