Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
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


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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01660906


Locations
Layout table for location information
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
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01660906     History of Changes
Other Study ID Numbers: CA180-400
2011‐006180‐21 ( EudraCT Number )
First Posted: August 9, 2012    Key Record Dates
Results First Posted: November 22, 2016
Last Update Posted: November 22, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Layout table for 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
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action