Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Dasatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

tablets, oral, 100 mg, Once daily, Up to12 months on study,

Bristol-Myers Squibb

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.

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

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

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.

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.

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.

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.

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.

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.

Study initiated: December 2012; Study Completion: October 2015

Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.

Dasatinib (100 mg)

Age, Continuous

< 65 years

>= 65 years

Age, Customized

Gender

White

Black or African American

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Other

Race/Ethnicity, Customized

CML-CP, chronic myeloid leukemia-chronic phase

Median Time Since CML-CP Diagnosis

Median Duration of Imatinib Treatment

< 400 milligrams

400 milligrams

Imatinib Dose at Baseline

MR4.5

CCyR

PCyR

Cytogenetic Test Not Performed

MR4.5, 4.5- log reduction in gene BCR-ABL transcript from the standardized baseline (0.0032% IS); MMR, Major Molecular Response = 3-log reduction in BCR-ABL gene transcripts from a standardized baseline; CCyR, complete cytogenetic response = criteria of 0% Philadelphia chromosome positive (Ph+) metaphases among cells in a bone marrow sample; PCyR, partial cytogenetic response = criteria of 1-35% Ph+ metaphases among cells in a bone marrow sample.

3 patients did not have cytogenetic testing performed at screening and thus baseline responses could not be classified to a response category

Best Baseline Response

Bristol-Myers Squibb Study Director

Resolved

Improved

Unchanged

Worsened

The Number of Imatinib-related Adverse Events (AEs) That Were Resolved, Improved, Remained Unchanged, or Worsened After 3 Months of Dasatinib Treatment

Core Symptom Severity Score, Month 3; n=37

Core Symptom Severity Score, Month 6; n=36

Core Symptom Severity Score, Month 12; n=37

Interference Score, Month 3; n=37

Interference Score, Month 6; n=35

Interference Score, Month 12; n=36

Symptom Severity Score, Month 3; n=37

Symptom Severity Score, Month 6; n=36

Symptom Severity Score, Month 12; n=37

CML-specific Symptom Severity Score, Month 3; n=37

CML-specific Symptom Severity Score, Month 6; n=36

CML-specific Symptom Severity Score,Month 12; n=36

5 Most Severe Symptom Score, Month 3; n=37

5 Most Severe Symptom Score, Month 6; n=36

5 Most Severe Symptom Score, Month 12; n=37

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

Global Health Status/QOL, Month 6; n=36

Global Health Status/QOL, Month 12; n=35

Cognitive Functioning, Month 6; n=35

Cognitive Functioning, Month 12; n=35

Emotional Functioning, Month 6; n=35

Emotional Functioning, Month 12; n=35

Physical Functioning, Month 6; n=36

Physical Functioning, Month 12; n=36

Role Functioning, Month 6; n=36

Role Functioning, Month 12; n=36

Social Functioning, Month 6; n=35

Social Functioning, Month 12; n=35

Fatigue, Month 6; n=36

Fatigue, Month 12; n=36

Nausea and Vomiting, Month 6; n=36

Nausea and Vomiting, Month 12; n=36

Pain, Month 6; n=36

Pain, Month 12; n=36

Appetite Loss, Month 6; n=35

Appetite Loss, Month 12; n=36

Constipation, Month 6; n=36

Constipation, Month 12; n=35

Diarrhoea, Month 6; n=36

Diarrhoea, Month 12; n=35

Dyspnoea, Month 6; n=36

Dyspnoea, Month 12; n=36

Financial Difficulties, Month 6; n=35

Financial Difficulties, Month 12; n=35

Insomnia, Month 6; n=36

Insomnia, Month 12; n=36

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

At least 1 AE

Discontinuation due to AE

Treatment-related AEs

SAEs

Treatment-related SAEs

Death

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

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

MMR, Month 6

MMR, Month 12

MR4.5, Month 6

MR4.5, Month 12

Number of Participants With a Major Molecular Response (MMR) and MR 4.5 After Switching to Dasatinib

Overall Study

Spots Global Cancer Trial Database for 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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial