Chronic Myeloid Leukemia, BCR-ABL1 Positive
Conditions
Brief summary
This randomized phase IIB trial studies imatinib mesylate at two different doses and dasatinib to see how well they work in treating patients with previously untreated chronic phase chronic myelogenous leukemia. Imatinib mesylate or dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To compare the molecular response rates, as measured by the decrease in breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcripts after 12 months of treatment, in patients with previously untreated chronic myelogenous leukemia (CML) in chronic phase who are treated with either dasatinib 100 mg/day or imatinib (STI571, Gleevec) (imatinib mesylate) 400 mg/day. II. To test whether increasing the dose of imatinib (STI571, Gleevec®) from 400 mg/day to 800 mg/day increases the rate of molecular response, as measured by the decrease in BCR-ABL transcripts after 12 months of treatment, in patients with previously untreated CML in chronic phase. III. To estimate rates of cytogenetic and hematologic responses to imatinib 400 mg/day, imatinib 800 mg/day, and dasatinib 100 mg/day. IV. To evaluate in a preliminary manner the prognostic effects of derivative (der)(9) and der(22) chromosomal deletions for response in CML patients treated with imatinib and dasatinib. V. To investigate in a preliminary manner changes in gene expression at relapse or progression compared to pre-treatment. VI. To estimate the frequency and severity of toxicities of the three treatment regimens. VII. To evaluate, in a preliminary manner, the overall survival and relapse-free survival of patients treated with these regimens. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive imatinib mesylate orally (PO) once daily (QD). Treatment repeats every 4 weeks for up to 5 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive imatinib mesylate PO twice daily (BID). Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive dasatinib PO BID. Treatment repeats every 4 weeks for up to 5 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 15 years.
Interventions
DRUGDasatinib
Given PO
DRUGImatinib Mesylate
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have CML in chronic phase based on bone marrow aspiration and biopsy and peripheral blood counts obtained within 28 days before registration * Patients must be registered on this study within 180 days after the date of first being diagnosed with CML, based on a cytogenetic or molecular analysis of peripheral blood or bone marrow, demonstrating the presence of the Philadelphia chromosome or variants of the (9;22) translocation or testing positive for Bcr-Abl by real time-polymerase chain reaction (RT-PCR); patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome and remain eligible * Patients must have Zubrod performance status 0-2 * Patients must not have received prior treatment for CML with the exception of hydroxyurea and/or anagrelide * Patients must not have received any prior chemotherapy regimen for peripheral blood stem cell mobilization; (prior collection of unmobilized peripheral blood stem cells is permitted) * Serum bilirubin =\< 2.0 x the institutional upper limit of the normal (IULN) * Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine transaminase (ALT) =\< 2.0 x the IULN * Patients (Southwestern Oncology Group \[SWOG\] institutions only) must be registered on SWOG-9007, "Cytogenetic Studies in Leukemia Patients;" collection of the pretreatment bone marrow specimen must be completed within 28 days prior to registration; the pretreatment bone marrow specimen must be submitted to an approved Southwest Oncology Group Cytogenetics Laboratory for cytogenetic analysis as described, and an aliquot of the bone marrow (or peripheral blood if the marrow aspiration is a dry tap) must be submitted for fluorescent in situ hybridization (FISH) analysis; note that protocol SWOG-9007 also requires submission of bone marrow specimens at the time of progression to the accelerated or blastic phase of CML or the loss of complete hematologic response and every six months while the patient is on this study * Patients (SWOG institutions only) must be registered on S9910, "Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary;" specimens of peripheral blood and bone marrow must be submitted to the Southwest Oncology Group Lymphoid Leukemia and CML Centralized Laboratory in Seattle, Washington; collection of pretreatment blood and marrow specimens must be completed within 28 days prior to registration; note that this study also requires submission of peripheral blood and bone marrow specimens at various times after entry into the study * Patients must not have undergone major surgery within 28 days before registration, and must have fully recovered from any other prior major surgery * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years * Patients must have an electrocardiogram (ECG) within 42 days prior to registration, and must not have any of the following cardiac symptoms prior to entry on study: * Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within 6 months of study entry * Diagnosed or suspected congenital long QT syndrome * Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) * Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\> 450 msec) * Uncontrolled hypertension * Patients must not have a history of significant bleeding disorder unrelated to cancer, including: * Congenital bleeding disorders (e.g., von Willebrand's disease) * Acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular Response Rate at 12 Months | pretreatment and after 12 months of treatment | Median value of baseline bcr-abl/bcr ratio from pretreatment was used as the baseline value for assessing each patient's molecular response. Molecular response criteria were: 1) not failed treatment on or before 12-month evaluation; 2) met criteria for hemalotogic response; 3) bcr-abl/bcr ration at 12-months must be 10,000 times smaller than the pretreatment ratio. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Response | 1 month after starting treatment | Hematologic response assesses whether patients' blood counts return to normal |
| 2-year Overall Survival (OS) | Every three months for the first year, every six months in years 2 and 3, and annually for years 4 and 5 | Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive. |
| Two Year Relapse-free Survival | every 3 months for the first year, every six months for years 2 and 3, annually for years 4 and 5 | Relapse-free survival is measured from the date of documented (possibly unconfirmed) hematologic complete remission until loss of hematologic complete remission or death from any cause. Observations are censored at the date of last contact for patients last known to be alive with report of loss of hematologic complete remission. |
| Toxicity | Patients were assessed for adverse events monthly every 4 weeks for the first year, every 6 months for years 2 and 3, and annually for years 4 and 5. | Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORBrian J Druker
SWOG Cancer Research Network
Participant flow
Recruitment details
Note that 403 patients were registered to the study. Three patients were registered to standard dose imatinib while concurrent randomization was occurring between standard dose imatinib, high dose imatinib, and dasatinib. Those three patients are included in both the standard dose imatinib A and B cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose Imatinib A Randomization between occurred between standard dose imatinib A and high dose imatinib | 72 |
| High Dose Imatinib | 73 |
| Dasatinib | 123 |
| Standard Dose Imatinib B Randomization occurred between Standard dose imatinib and dasatinib | 123 |
| Total | 391 |
Baseline characteristics
| Characteristic | Standard Dose Imatinib A | High Dose Imatinib | Dasatinib | Standard Dose Imatinib B | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50 years | 52 years | 47 years | 50 years | 50 years |
| Region of Enrollment United States | 72 participants | 73 participants | 123 participants | 123 participants | 391 participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 48 Participants | 51 Participants | 151 Participants |
| Sex: Female, Male Male | 46 Participants | 47 Participants | 75 Participants | 72 Participants | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| other Total, other adverse events | 71 / 72 | 72 / 72 | 115 / 122 | 120 / 123 |
| serious Total, serious adverse events | 4 / 72 | 0 / 72 | 20 / 122 | 0 / 123 |
Outcome results
Primary
Molecular Response Rate at 12 Months
Median value of baseline bcr-abl/bcr ratio from pretreatment was used as the baseline value for assessing each patient's molecular response. Molecular response criteria were: 1) not failed treatment on or before 12-month evaluation; 2) met criteria for hemalotogic response; 3) bcr-abl/bcr ration at 12-months must be 10,000 times smaller than the pretreatment ratio.
Time frame: pretreatment and after 12 months of treatment
Population: Patients with follow-up specimens assayed by reverse transcription polymerase chain reaction (RT-PCR)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Imatinib A | Molecular Response Rate at 12 Months | 5 participants |
| High Dose Imatinib | Molecular Response Rate at 12 Months | 14 participants |
| Dasatinib | Molecular Response Rate at 12 Months | 27 participants |
| Standard Dose Imatinib B | Molecular Response Rate at 12 Months | 18 participants |
p-value: 0.073Fisher Exact
p-value: 0.31Fisher Exact
Secondary
2-year Overall Survival (OS)
Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive.
Time frame: Every three months for the first year, every six months in years 2 and 3, and annually for years 4 and 5
Population: All eligible patients who were treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Imatinib A | 2-year Overall Survival (OS) | 89 Percent of population |
| High Dose Imatinib | 2-year Overall Survival (OS) | 95 Percent of population |
| Dasatinib | 2-year Overall Survival (OS) | 97 Percent of population |
| Standard Dose Imatinib B | 2-year Overall Survival (OS) | 98 Percent of population |
Comparison: Log-rank test of overall survivalp-value: 0.29Log Rank
Comparison: Log-rank test of overall survivalp-value: 0.55Log Rank
Secondary
Hematologic Response
Hematologic response assesses whether patients' blood counts return to normal
Time frame: 1 month after starting treatment
Population: Eligible, treated patients who were evaluable for hematologic response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Imatinib A | Hematologic Response | 63 participants |
| High Dose Imatinib | Hematologic Response | 66 participants |
| Dasatinib | Hematologic Response | 107 participants |
| Standard Dose Imatinib B | Hematologic Response | 112 participants |
Secondary
Toxicity
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
Time frame: Patients were assessed for adverse events monthly every 4 weeks for the first year, every 6 months for years 2 and 3, and annually for years 4 and 5.
Population: Eligible patients who started therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Dose Imatinib A | Toxicity | Hypertension | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Febrile neutropenia | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Weight gain | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Abdomen NOS | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Hypoxia | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Syncope (fainting) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pericardial effusion (non-malignant) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pleural effusion (non-malignant) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infection with Grade 3 or 4 neutrophils - Blood | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 8 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infection with Grade 3/4 neut - Lung (pneumon | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Hot flashes/flushes | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Potassium, serum-low (hypokalemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Restrictive cardiomyopathy | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Colon | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Dyspnea (shortness of breath) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Scrotum | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Fatigue (asthenia, lethargy, malaise) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | CNS cerebrovascular ischemia | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Neuropathy: sensory | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infect with norm ANC or Grade 1 or 2 neut - Sinus | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Glucose, serum-high (hyperglycemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Distention/bloating, abdominal | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Vaginal mucositis | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Inf with no ANC or Grade 1/2 neut - Ur tract NOS | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Rash/desquamation | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Proteinuria | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Neuropathy: motor | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Infection with unknown ANC - Sinus | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Inf with no ANC or Grade 1/2 netLung (pneumonia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Potassium, serum-high (hyperkalemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Edema: head and neck | 2 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Left ventricular diastolic dysfunction | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Rash: acne/acneiform | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Vision-blurred vision | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | CPK (creatine phosphokinase) | 3 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Nausea | 2 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Joint | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Edema: limb | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Chest/thorax NOS | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Retinal detachment | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Dehydration | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Muscle weak, not due to neurop. Whole body/general | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Extremity-limb | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Bilirubin (hyperbilirubinemia) | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Cardiac-ischemia/infarction | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Dizziness | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Head/headache | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Edema: trunk/genital | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | GGT (gamma-glutamyl transpeptidase) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Mood alteration - depression | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Sodium, serum-high (hypernatremia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Muscle | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Vomiting | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Bone | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Edema: viscera | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Conduction abnor/Atrioventricular heart block | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | AST, SGOT (serum glutamic oxaloacetic trans.) | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Metabolic/Laboratory-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Constipation | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Phosphate, serum-low (hypophosphatemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Hematoma | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Colitis | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Hepatobiliary/Pancreas-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Platelets | 6 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Watery eye (epiphora, tearing) | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pain - Back | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Hemoglobin | 5 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Lymphopenia | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Prolonged QTc interval | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pruritus/itching | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Bronchospasm, wheezing | 0 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Diarrhea | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Leukocytes (total WBC) | 1 Participants with a given type of AE |
| Standard Dose Imatinib A | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain-Other (Specify) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Inf with no ANC or Grade 1/2 netLung (pneumonia) | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Rash/desquamation | 4 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Conduction abnor/Atrioventricular heart block | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Rash: acne/acneiform | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infection with Grade 3 or 4 neutrophils - Blood | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Restrictive cardiomyopathy | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pericardial effusion (non-malignant) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hepatobiliary/Pancreas-Other (Specify) | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Retinal detachment | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Glucose, serum-high (hyperglycemia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Syncope (fainting) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Constipation | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Vaginal mucositis | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 3 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | GGT (gamma-glutamyl transpeptidase) | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Vision-blurred vision | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Vomiting | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Dizziness | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Febrile neutropenia | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Watery eye (epiphora, tearing) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Weight gain | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Fatigue (asthenia, lethargy, malaise) | 11 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hot flashes/flushes | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Distention/bloating, abdominal | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Dyspnea (shortness of breath) | 2 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Proteinuria | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Joint | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Edema: head and neck | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Prolonged QTc interval | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Edema: limb | 2 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Bone | 3 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Edema: trunk/genital | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Edema: viscera | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Back | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hematoma | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Potassium, serum-low (hypokalemia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hemoglobin | 8 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Abdomen NOS | 4 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hypertension | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Bronchospasm, wheezing | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Hypoxia | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | AST, SGOT (serum glutamic oxaloacetic trans.) | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 12 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infection with Grade 3/4 neut - Lung (pneumon | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Neuropathy: sensory | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Colon | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Scrotum | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infect with norm ANC or Grade 1 or 2 neut - Sinus | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | CNS cerebrovascular ischemia | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Neuropathy: motor | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Inf with no ANC or Grade 1/2 neut - Ur tract NOS | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Infection with unknown ANC - Sinus | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Nausea | 2 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Left ventricular diastolic dysfunction | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | CPK (creatine phosphokinase) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Muscle weak, not due to neurop. Whole body/general | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Chest/thorax NOS | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Extremity-limb | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Mood alteration - depression | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Head/headache | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Cardiac-ischemia/infarction | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pain - Muscle | 3 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Dehydration | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Metabolic/Laboratory-Other (Specify) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pleural effusion (non-malignant) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Sodium, serum-high (hypernatremia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Phosphate, serum-low (hypophosphatemia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Lymphopenia | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Platelets | 14 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Potassium, serum-high (hyperkalemia) | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Colitis | 0 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Leukocytes (total WBC) | 2 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Pruritus/itching | 1 Participants with a given type of AE |
| High Dose Imatinib | Toxicity | Diarrhea | 6 Participants with a given type of AE |
| Dasatinib | Toxicity | Proteinuria | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Diarrhea | 6 Participants with a given type of AE |
| Dasatinib | Toxicity | Dehydration | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | AST, SGOT (serum glutamic oxaloacetic trans.) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Bronchospasm, wheezing | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | CNS cerebrovascular ischemia | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | CPK (creatine phosphokinase) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Cardiac-ischemia/infarction | 2 Participants with a given type of AE |
| Dasatinib | Toxicity | Colitis | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Conduction abnor/Atrioventricular heart block | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Constipation | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Dizziness | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Dyspnea (shortness of breath) | 7 Participants with a given type of AE |
| Dasatinib | Toxicity | Edema: head and neck | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Edema: limb | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Edema: trunk/genital | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Edema: viscera | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Hematoma | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Hemoglobin | 12 Participants with a given type of AE |
| Dasatinib | Toxicity | Hypertension | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Hypoxia | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Infection with Grade 3/4 neut - Lung (pneumon | 2 Participants with a given type of AE |
| Dasatinib | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Scrotum | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Infect with norm ANC or Grade 1 or 2 neut - Sinus | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Inf with no ANC or Grade 1/2 neut - Ur tract NOS | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Infection with unknown ANC - Sinus | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Bone | 2 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Chest/thorax NOS | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Extremity-limb | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Head/headache | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Muscle | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain-Other (Specify) | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Phosphate, serum-low (hypophosphatemia) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Potassium, serum-high (hyperkalemia) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Pruritus/itching | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Sodium, serum-high (hypernatremia) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Rash/desquamation | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Rash: acne/acneiform | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Restrictive cardiomyopathy | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Retinal detachment | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Syncope (fainting) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Vaginal mucositis | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Vision-blurred vision | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Vomiting | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Watery eye (epiphora, tearing) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Weight gain | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Hot flashes/flushes | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Distention/bloating, abdominal | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Fatigue (asthenia, lethargy, malaise) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Febrile neutropenia | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | GGT (gamma-glutamyl transpeptidase) | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Glucose, serum-high (hyperglycemia) | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Hepatobiliary/Pancreas-Other (Specify) | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Infection with Grade 3 or 4 neutrophils - Blood | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Colon | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Inf with no ANC or Grade 1/2 netLung (pneumonia) | 2 Participants with a given type of AE |
| Dasatinib | Toxicity | Left ventricular diastolic dysfunction | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Leukocytes (total WBC) | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Lymphopenia | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Metabolic/Laboratory-Other (Specify) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Mood alteration - depression | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pericardial effusion (non-malignant) | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Muscle weak, not due to neurop. Whole body/general | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Nausea | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Neuropathy: motor | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Neuropathy: sensory | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 18 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Abdomen NOS | 3 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Back | 0 Participants with a given type of AE |
| Dasatinib | Toxicity | Pain - Joint | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Platelets | 22 Participants with a given type of AE |
| Dasatinib | Toxicity | Pleural effusion (non-malignant) | 4 Participants with a given type of AE |
| Dasatinib | Toxicity | Potassium, serum-low (hypokalemia) | 1 Participants with a given type of AE |
| Dasatinib | Toxicity | Prolonged QTc interval | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Colon | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Rash/desquamation | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Conduction abnor/Atrioventricular heart block | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Inf with no ANC or Grade 1/2 netLung (pneumonia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pericardial effusion (non-malignant) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Left ventricular diastolic dysfunction | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pruritus/itching | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Proteinuria | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Prolonged QTc interval | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Leukocytes (total WBC) | 3 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Potassium, serum-high (hyperkalemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Phosphate, serum-low (hypophosphatemia) | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Platelets | 11 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Lymphopenia | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain-Other (Specify) | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Muscle | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Colitis | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Metabolic/Laboratory-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Head/headache | 3 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Extremity-limb | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Cardiac-ischemia/infarction | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Mood alteration - depression | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Chest/thorax NOS | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Bone | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Constipation | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pleural effusion (non-malignant) | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Muscle weak, not due to neurop. Whole body/general | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infection with unknown ANC - Sinus | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | CNS cerebrovascular ischemia | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Nausea | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Inf with no ANC or Grade 1/2 neut - Ur tract NOS | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infect with norm ANC or Grade 1 or 2 neut - Sinus | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Bronchospasm, wheezing | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Neuropathy: motor | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infec with norm ANC or Grade 1 or 2 neut - Scrotum | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infection with Grade 3/4 neut - Lung (pneumon | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Neuropathy: sensory | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Infection with Grade 3 or 4 neutrophils - Blood | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hypoxia | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 3 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 15 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hypertension | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hemoglobin | 5 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Potassium, serum-low (hypokalemia) | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Abdomen NOS | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hematoma | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Glucose, serum-high (hyperglycemia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | AST, SGOT (serum glutamic oxaloacetic trans.) | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Diarrhea | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | CPK (creatine phosphokinase) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Back | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Distention/bloating, abdominal | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Edema: viscera | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hot flashes/flushes | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Weight gain | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Edema: trunk/genital | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Fatigue (asthenia, lethargy, malaise) | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Watery eye (epiphora, tearing) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Vomiting | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Edema: limb | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Febrile neutropenia | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Vision-blurred vision | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Vaginal mucositis | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Edema: head and neck | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | GGT (gamma-glutamyl transpeptidase) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Syncope (fainting) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Sodium, serum-high (hypernatremia) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Dyspnea (shortness of breath) | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Retinal detachment | 1 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Restrictive cardiomyopathy | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Dehydration | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Hepatobiliary/Pancreas-Other (Specify) | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Rash: acne/acneiform | 0 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Pain - Joint | 2 Participants with a given type of AE |
| Standard Dose Imatinib B | Toxicity | Dizziness | 1 Participants with a given type of AE |
Secondary
Two Year Relapse-free Survival
Relapse-free survival is measured from the date of documented (possibly unconfirmed) hematologic complete remission until loss of hematologic complete remission or death from any cause. Observations are censored at the date of last contact for patients last known to be alive with report of loss of hematologic complete remission.
Time frame: every 3 months for the first year, every six months for years 2 and 3, annually for years 4 and 5
Population: Eligible, treated patients who achieved a hematologic complete remission
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Imatinib A | Two Year Relapse-free Survival | 83 Percent of population |
| High Dose Imatinib | Two Year Relapse-free Survival | 97 Percent of population |
| Dasatinib | Two Year Relapse-free Survival | 96 Percent of population |
| Standard Dose Imatinib B | Two Year Relapse-free Survival | 95 Percent of population |
Comparison: Log-rank test of relapse-free survivalp-value: 0.074Log Rank
Comparison: Log-rank test of relapse-free survivalp-value: 0.29Log Rank