Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

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, dasatinib 50-140 mg once daily (QD)

Imatinib

Bristol-Myers Squibb

The purpose of this clinical research study is to compare the confirmed complete cytogenetic response of dasatinib with that of imatinib within 12 months after randomization in patients with newly diagnosed chronic-phase Philadelphia positive chronic myeloid leukemia. The safety of this treatment will also be studied.

A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL®) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

ULN=upper limit of normal. Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil count: Grade 3 \<1000-500/mm\^3; Grade 4 \<500/mm\^3. Hemoglobin: Grade 3 \<8.0-6.5 g/dL; Grade 4 \<6.5 g/dL. Platelets: Grade 3 \<50,000-25,000/mm\^3; Grade 4 \<25,000/mm\^3. ALT/AST: Grade 3 \>5.0-20\*ULN; Grade 4 \>20\*ULN. Total bilirubin: Grade 3 \>3-10\*ULN; Grade 4 \>10\*ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total bilirubin: 0.0-1.0 mg/dL. Creatinine: Grade 3 \>3.0-6.0\*ULN; Grade 4 \>6.0\*ULN. Phosphate: Grade 3 \<2.0-1.0 mg/dL; Grade 4 \<1.0 mg/dL. Calcium: Grade 3 \<7.0-6.0 mg/dL; Grade 4 \<6.0 mg/dL. Potassium: Grade 3 \<3.0-2.5 mmol/L; Grade 4 \<2.5 mmol/L.

Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR.

Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR.

Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1.

Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants.

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The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants.

PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.

OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.

Study initiated: September 2007; End of Study: December 2015

Tablets, oral, dasatinib 100 mg once daily (QD)

Tablets, oral, imatinib 400 mg once daily (QD)

Total

Age, Continuous

<20 years

Between 21 and 45 years

Between 46 and 65 years

Between 66 and 75 years

>75 years

Age, Customized

Gender

White

Black/African American

Asian

Other

Race/Ethnicity, Customized

ECOG score=0

ECOG score=1

ECOG score=2

ECOG is a 6-item scale used to assess disease progression, daily functioning, and appropriate treatment and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all predisease performance without restriction and (worst score) 5=death.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Number of Patients With Liver Involvement

Number of Participants With Spleen Involvement

BMS Study Director

Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months

At Year 2

At Year 3

At Year 4

At Year 5

All randomized participants who achieved cCCyR

Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR)

Percentage of Participants With Major Molecular Response (MMR) at Any Time

Hazard Ratio and Confidence Interval were based on analyses on all randomized subjects

Time to Confirmed Complete Cytogenic Response (cCCyR) Overall

Hazard Ratio, and Confidence Interval were based on analyses on all randomized subjects

All participants who received treatment and achieved MMR

Time to Major Molecular Response (MMR) Overall

Percentage of Participants With Progression-free Survival (PFS)

Percentage of Participants With Overall Survival (OS)

All AEs

All Drug-related AEs

Diarrhea

Pleural effusion

Nausea

Cough

Muscle spasms

Thrombocytopenia

Neutropenia

Headache

Pyrexia

Vomiting

SAEs

Drug-related SAEs

AEs leading to discontinuation

All deaths

Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths

Grade 3/4 Absolute neutrophil count

Grade 3/4 Hemoglobin

Grade 3/4 Platelets

Grade 3/4 Alanine aminotransferase (ALT)

Grade 3/4 Aspartate aminotransferase (AST)

Grade 3/4 Total bilirubin

Grade 3/4 Creatinine

Grade 3/4 Phosphate

Grade 3/4 Calcium

Grade 3/4 Potassium

Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results

Tablets, oral, imatinib 400mg once daily (QD)

Overall Study

Spots Global Cancer Trial Database for chronic phase philadelphia chromosome positive chronic myeloid leukemia