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Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00154375
Collaborator
(none)
240
Enrollment
1
Location
2
Arms

Study Details

Study Description

Brief Summary

This is a Phase III study comparing Imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
240 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
Study Start Date :
Oct 1, 2004
Actual Primary Completion Date :
Aug 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Imatinib mesylate + hydroxyurea (HU)

Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening.

Drug: Imatinib mesylate
Imatinib was supplied as 100 mg and 400 mg tablets packaged in polyethylene bottles.
Other Names:
  • Glivec®

    • Drug: Hydroxyurea
    Other Names:
  • Litalir®

    		•
    Active Comparator: Hydroxyurea alone

    1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.

    Drug: Hydroxyurea
    Other Names:
  • Litalir®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Progression Free Survival (PFS) During the Study Duration [6 months -1 year]

      PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).

    Secondary Outcome Measures

    1. Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations [6 months - 1 year]

      National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Signed informed consent prior to initiation of any study procedure.

    • Patients >= 18 years of age.

    • Histological confirmed diagnosis of glioblastoma multiforme / astrocytoma World Health Organization (WHO) grade IV by a reference pathologist

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.

    • Adequate hepatic, renal and bone marrow function as defined by the following: total bilirubin < 1.5 x Upper Limit of Normal (ULN), ALT and AST < 2.5 x ULN, creatinine < 1.5 x ULN, absolute neutrophil count > 1.5 x109/L, platelets > 100 x109/L and hemoglobin > 10 g/dL.

    • Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential who agree to employ an effective barrier method of birth control throughout the study, and for up to 3 months following discontinuation of study drug.

    • Life expectancy of >3 months.

    • MRI available every 6 weeks for disease management

    • No intercerebral inflammation

    • Irradiation therapy 54 to 62 gy finished or less according to national standard

    • Chemotherapy at least 1 temozolomide containing regimen finished, no established chemotherapy regiment available and progression under chemotherapy or in between 6 months following the last chemotherapy.

    • Leucocytes > 2.500/µl, to be controlled once a week

    • Thrombocytes > 80.000/µl, to be controlled once a week

    • Ensured compliance

    • Patients who had a second or third resection after disease progression cannot be included earlier than 2 weeks following the resection. MRI should be performed not later than 72 h post operation. If patients are to be included later than 4 weeks after the resection, a new baseline MRI must be performed.

    Exclusion Criteria:

    • Female patients who are pregnant or breast-feeding.

    • Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug.

    • Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina or Grade 3 or 4 cardiac problems as defined by the New York Heart Association Criteria.

    • Patients with other malignant disorders.

    • Patient with acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis).

    • Patients who are known to be HIV positive (no specific tests are required for confirmation of eligibility).

    • Expected incompliance according to treatment, treatment diary and examination schedule

    • Not confirmed histological diagnosis glioblastoma multiforme/astrocytoma WHO grade IV

    • Other drugs with potential cytostatic main or side effect

    • No or inadequate chemotherapy or irradiation therapy

    • Patients without hematological recovery after previous chemotherapy who have been treated with Chemotherapy within 28 days of the first day of administration of study drug.

    Other protocol-specific inclusion /exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Duelmen Germany

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00154375
    Other Study ID Numbers:
    • CSTI571BDE40
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Apr 26, 2011
    Last Verified:
    Apr 1, 2011
    Keywords provided by , ,
    Open label
    Imatinib mesylate
    hydroxyurea
    temozolomide
    resistant
    protein tyrosine kinases
    adenocarcinoma
    glioblastoma multiforme
    astrocytoma
    brain tumor
    brain cancer
    Additional relevant MeSH terms:
    Glioblastoma
    Astrocytoma
    Imatinib Mesylate
    Hydroxyurea

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Imatinib Mesylate + Hydroxyurea (HU) Hydroxyurea Alone
    Arm/Group Description Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. 1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.
    Period Title: Overall Study
    STARTED 120 120
    Discontinued Study Treatment 111 104
    Not Exposed to Study Treatment 2 2
    COMPLETED 7 14
    NOT COMPLETED 113 106

    Baseline Characteristics

    Arm/Group Title Imatinib Mesylate + Hydroxyurea (HU) Hydroxyurea Alone Total
    Arm/Group Description Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. 1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea. Total of all reporting groups
    Overall Participants 120 120 240
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.1
    (11.3)
    50.2
    (11.4)
    51.2
    (11.4)
    Sex: Female, Male (Count of Participants)
    Female
    50
    41.7%
    38
    31.7%
    88
    36.7%
    Male
    70
    58.3%
    82
    68.3%
    152
    63.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Progression Free Survival (PFS) During the Study Duration
    Description PFS was defined as the time from the date of randomization to the date of the first documented progression according to the MacDonald criteria, or death due to any cause. MacDonald criteria are standard criteria in neurooncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).
    Time Frame 6 months -1 year

    Outcome Measure Data

    Analysis Population Description
    The ITT population consists of all randomized patients, analyzed according to their randomized treatment.
    Arm/Group Title Imatinib Mesylate + Hydroxyurea (HU) Hydroxyurea Alone
    Arm/Group Description Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. 1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.
    Measure Participants 120 120
    6 months
    5.3
    4.4%
    6.6
    5.5%
    12 months
    2.1
    1.8%
    2.1
    1.8%
    2. Secondary Outcome
    Title Number of Participants With Death, Other Serious or Clinically Significant Adverse Events (AEs) or Related Discontinuations
    Description National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each AE term. Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. According to FDA 21CFR 314.80, a serious adverse event (SAE) is described as any adverse event that leads to death, is life threatening ( NIH criteria Grade 4), causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
    Time Frame 6 months - 1 year

    Outcome Measure Data

    Analysis Population Description
    The safety population consisted of randomized patients with at least one dose of randomized medication.
    Arm/Group Title Imatinib Mesylate + Hydroxyurea (HU) Hydroxyurea Alone
    Arm/Group Description Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Every 6 weeks after randomization based on assessment of therapeutic response, either patients continued with above mentioned dosing regimen or switched to receive a daily dose of 800 mg imatinib with 1000 mg HU. Patients were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. 1500 mg/day of HU given as 500 mg 3 times daily. Every 6 weeks after randomization and based on assessment of therapeutic response, the patients were either switched to combination arm or continued in monotherapy arm of hydroxyurea.
    Measure Participants 118 118
    Deaths
    84
    70%
    91
    75.8%
    Death due to disease progression
    76
    63.3%
    77
    64.2%
    Serious Adverse Events (SAEs)
    64
    53.3%
    79
    65.8%
    NCI/NIH Grade 3 (severe) or 4 (life threatening)
    54
    45%
    64
    53.3%
    Suspected to be drug-related
    12
    10%
    12
    10%
    Leading to dose adjustment or interruption
    6
    5%
    16
    13.3%
    Leading to permanent discontinuation
    9
    7.5%
    13
    10.8%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Safety population = patients who were randomized to either Imatinib + Hydroxyurea (combination)[n=118] or to Hydroxyurea alone [n=118]. Every 6 wks, patients on Hydroxyurea alone switched to combination arm depending on response. So, for the safety analysis Hydroxyurea arm is divided into Hydroxyurea alone [n=118] or switch to combination [n=85].
    Arm/Group Title Imatinib Mesylate + Hydroxyurea (HU) Period With Hydroxyurea Alone Period After Switch to Combination
    Arm/Group Description Imatinib was supplied as 100 mg and 400 mg tablets. Patients in the combination arm were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time). Patients receiving a daily dose of 800 mg imatinib with 1000 mg HU were instructed to split the intake, taking 400 mg imatinib with 500 mg HU in the morning, then the same in the evening. 1500 mg/day of HU given as 500 mg 3 times daily. After every 6 weeks from randomization, depending on the assessment of therapeutic effect, patients were switched from Hydroxyurea (1500 mg/day p.o) to combination arm where patients were instructed to take a daily oral imatinib dose of 600 mg (600 mg at lunch time) and a daily oral hydroxyurea (HU) dose of 1000 mg (500 mg twice daily; in the morning and at bed time).
    All Cause Mortality
    Imatinib Mesylate + Hydroxyurea (HU) Period With Hydroxyurea Alone Period After Switch to Combination
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Imatinib Mesylate + Hydroxyurea (HU) Period With Hydroxyurea Alone Period After Switch to Combination
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 64/118 (54.2%) 46/118 (39%) 49/85 (57.6%)
    Blood and lymphatic system disorders
    ANAEMIA 2/118 (1.7%) 0/118 (0%) 0/85 (0%)
    LEUKOPENIA 1/118 (0.8%) 2/118 (1.7%) 5/85 (5.9%)
    NEUTROPENIA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    THROMBOCYTOPENIA 3/118 (2.5%) 0/118 (0%) 2/85 (2.4%)
    Cardiac disorders
    CARDIAC FAILURE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Eye disorders
    VISUAL ACUITY REDUCED 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    VISUAL DISTURBANCE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 2/118 (1.7%) 0/118 (0%) 1/85 (1.2%)
    DYSPHAGIA 1/118 (0.8%) 0/118 (0%) 1/85 (1.2%)
    NAUSEA 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    STOMATITIS 2/118 (1.7%) 0/118 (0%) 0/85 (0%)
    VOMITING 1/118 (0.8%) 2/118 (1.7%) 0/85 (0%)
    General disorders
    APLASIA 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    ASTHENIA 0/118 (0%) 1/118 (0.8%) 1/85 (1.2%)
    CHEST PAIN 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    DEATH 1/118 (0.8%) 1/118 (0.8%) 2/85 (2.4%)
    FATIGUE 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    GENERAL PHYSICAL HEALTH DETERIORATION 7/118 (5.9%) 6/118 (5.1%) 2/85 (2.4%)
    NECROSIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    OEDEMA PERIPHERAL 1/118 (0.8%) 0/118 (0%) 1/85 (1.2%)
    PAIN 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PERFORMANCE STATUS DECREASED 1/118 (0.8%) 1/118 (0.8%) 0/85 (0%)
    PYREXIA 1/118 (0.8%) 1/118 (0.8%) 1/85 (1.2%)
    SUDDEN DEATH 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    Infections and infestations
    ASPERGILLOSIS 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    BRONCHITIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    GASTROENTERITIS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    HERPES ZOSTER 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    INJECTION SITE ABSCESS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    LOWER RESPIRATORY TRACT INFECTION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PNEUMONIA 9/118 (7.6%) 4/118 (3.4%) 5/85 (5.9%)
    PNEUMONIA PRIMARY ATYPICAL 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    PULMONARY SEPSIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    SEPSIS 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    SINUSITIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    STAPHYLOCOCCAL BACTERAEMIA 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    SUBCUTANEOUS ABSCESS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    URINARY TRACT INFECTION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    VULVITIS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Injury, poisoning and procedural complications
    BRAIN CONTUSION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    FALL 3/118 (2.5%) 1/118 (0.8%) 3/85 (3.5%)
    HEAD INJURY 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    RADIUS FRACTURE 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    SUBDURAL HAEMATOMA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    SUBDURAL HAEMORRHAGE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    THORACIC VERTEBRAL FRACTURE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    BLOOD LACTATE DEHYDROGENASE INCREASED 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    GENERAL PHYSICAL CONDITION ABNORMAL 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    HEPATIC ENZYME INCREASED 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Metabolism and nutrition disorders
    DEHYDRATION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    HYPERGLYCAEMIA 2/118 (1.7%) 2/118 (1.7%) 0/85 (0%)
    HYPOKALAEMIA 1/118 (0.8%) 0/118 (0%) 1/85 (1.2%)
    HYPONATRAEMIA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    BACK PAIN 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    BURSITIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    MUSCLE SPASMS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    MUSCULAR WEAKNESS 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    INTRACRANIAL TUMOUR HAEMORRHAGE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    NEOPLASM PROGRESSION 4/118 (3.4%) 0/118 (0%) 1/85 (1.2%)
    Nervous system disorders
    ALTERED STATE OF CONSCIOUSNESS 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    APHASIA 4/118 (3.4%) 0/118 (0%) 0/85 (0%)
    APRAXIA 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    BALANCE DISORDER 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    BRAIN OEDEMA 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    CEREBRAL HAEMORRHAGE 1/118 (0.8%) 0/118 (0%) 1/85 (1.2%)
    CONVULSION 3/118 (2.5%) 4/118 (3.4%) 4/85 (4.7%)
    COORDINATION ABNORMAL 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    DEMENTIA 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    DEPRESSED LEVEL OF CONSCIOUSNESS 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    DISTURBANCE IN ATTENTION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    DIZZINESS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    DYSPHASIA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    EPILEPSY 5/118 (4.2%) 9/118 (7.6%) 9/85 (10.6%)
    HEADACHE 2/118 (1.7%) 5/118 (4.2%) 3/85 (3.5%)
    HEMIPARESIS 8/118 (6.8%) 5/118 (4.2%) 2/85 (2.4%)
    HEMIPLEGIA 1/118 (0.8%) 2/118 (1.7%) 0/85 (0%)
    INTRACRANIAL PRESSURE INCREASED 3/118 (2.5%) 3/118 (2.5%) 4/85 (4.7%)
    LOSS OF CONSCIOUSNESS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    NERVOUS SYSTEM DISORDER 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    PARESIS 1/118 (0.8%) 1/118 (0.8%) 1/85 (1.2%)
    PARTIAL SEIZURES 1/118 (0.8%) 2/118 (1.7%) 4/85 (4.7%)
    PSYCHOMOTOR SKILLS IMPAIRED 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    SOMNOLENCE 2/118 (1.7%) 1/118 (0.8%) 0/85 (0%)
    SPEECH DISORDER 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Psychiatric disorders
    ABNORMAL BEHAVIOUR 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    AGITATION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    ANXIETY 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    CONFUSIONAL STATE 4/118 (3.4%) 0/118 (0%) 1/85 (1.2%)
    HALLUCINATION 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    MENTAL DISORDER 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PERSONALITY DISORDER 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Renal and urinary disorders
    INCONTINENCE 0/118 (0%) 0/118 (0%) 2/85 (2.4%)
    OLIGURIA 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    RENAL COLIC 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA 3/118 (2.5%) 3/118 (2.5%) 2/85 (2.4%)
    EPISTAXIS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PLEURAL EFFUSION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PNEUMONIA ASPIRATION 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    PNEUMONITIS 0/118 (0%) 0/118 (0%) 1/85 (1.2%)
    PULMONARY EMBOLISM 1/118 (0.8%) 1/118 (0.8%) 2/85 (2.4%)
    RESPIRATORY FAILURE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Skin and subcutaneous tissue disorders
    DECUBITUS ULCER 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    Surgical and medical procedures
    BRAIN LOBECTOMY 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    CYSTOSTOMY 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    TUMOUR EXCISION 3/118 (2.5%) 0/118 (0%) 0/85 (0%)
    Vascular disorders
    CIRCULATORY COLLAPSE 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    DEEP VEIN THROMBOSIS 1/118 (0.8%) 0/118 (0%) 0/85 (0%)
    HYPERTENSION 0/118 (0%) 1/118 (0.8%) 0/85 (0%)
    THROMBOSIS 0/118 (0%) 1/118 (0.8%) 1/85 (1.2%)
    VENOUS THROMBOSIS 1/118 (0.8%) 0/118 (0%) 1/85 (1.2%)
    Other (Not Including Serious) Adverse Events
    Imatinib Mesylate + Hydroxyurea (HU) Period With Hydroxyurea Alone Period After Switch to Combination
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 104/118 (88.1%) 80/118 (67.8%) 65/85 (76.5%)
    Blood and lymphatic system disorders
    ANAEMIA 13/118 (11%) 8/118 (6.8%) 13/85 (15.3%)
    LEUKOPENIA 16/118 (13.6%) 14/118 (11.9%) 14/85 (16.5%)
    THROMBOCYTOPENIA 24/118 (20.3%) 15/118 (12.7%) 17/85 (20%)
    Endocrine disorders
    CUSHINGOID 6/118 (5.1%) 1/118 (0.8%) 5/85 (5.9%)
    Gastrointestinal disorders
    ABDOMINAL PAIN 6/118 (5.1%) 3/118 (2.5%) 2/85 (2.4%)
    ABDOMINAL PAIN UPPER 7/118 (5.9%) 1/118 (0.8%) 0/85 (0%)
    CONSTIPATION 11/118 (9.3%) 4/118 (3.4%) 5/85 (5.9%)
    DIARRHOEA 11/118 (9.3%) 4/118 (3.4%) 4/85 (4.7%)
    DYSPEPSIA 2/118 (1.7%) 6/118 (5.1%) 2/85 (2.4%)
    NAUSEA 28/118 (23.7%) 17/118 (14.4%) 10/85 (11.8%)
    VOMITING 21/118 (17.8%) 13/118 (11%) 6/85 (7.1%)
    General disorders
    ASTHENIA 11/118 (9.3%) 6/118 (5.1%) 9/85 (10.6%)
    FATIGUE 34/118 (28.8%) 16/118 (13.6%) 18/85 (21.2%)
    GENERAL PHYSICAL HEALTH DETERIORATION 10/118 (8.5%) 8/118 (6.8%) 4/85 (4.7%)
    OEDEMA PERIPHERAL 29/118 (24.6%) 12/118 (10.2%) 14/85 (16.5%)
    PYREXIA 6/118 (5.1%) 1/118 (0.8%) 2/85 (2.4%)
    Injury, poisoning and procedural complications
    FALL 4/118 (3.4%) 3/118 (2.5%) 5/85 (5.9%)
    Investigations
    BLOOD LACTATE DEHYDROGENASE INCREASED 6/118 (5.1%) 6/118 (5.1%) 1/85 (1.2%)
    Metabolism and nutrition disorders
    ANOREXIA 6/118 (5.1%) 2/118 (1.7%) 1/85 (1.2%)
    HYPOKALAEMIA 14/118 (11.9%) 2/118 (1.7%) 6/85 (7.1%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 6/118 (5.1%) 3/118 (2.5%) 4/85 (4.7%)
    BACK PAIN 4/118 (3.4%) 2/118 (1.7%) 6/85 (7.1%)
    MUSCULAR WEAKNESS 13/118 (11%) 5/118 (4.2%) 3/85 (3.5%)
    PAIN IN EXTREMITY 6/118 (5.1%) 4/118 (3.4%) 2/85 (2.4%)
    Nervous system disorders
    AMNESIA 8/118 (6.8%) 2/118 (1.7%) 4/85 (4.7%)
    APHASIA 9/118 (7.6%) 4/118 (3.4%) 5/85 (5.9%)
    CONVULSION 6/118 (5.1%) 2/118 (1.7%) 6/85 (7.1%)
    COORDINATION ABNORMAL 9/118 (7.6%) 9/118 (7.6%) 6/85 (7.1%)
    DIZZINESS 16/118 (13.6%) 3/118 (2.5%) 7/85 (8.2%)
    EPILEPSY 13/118 (11%) 3/118 (2.5%) 3/85 (3.5%)
    HEADACHE 26/118 (22%) 24/118 (20.3%) 16/85 (18.8%)
    HEMIPARESIS 10/118 (8.5%) 7/118 (5.9%) 7/85 (8.2%)
    LETHARGY 6/118 (5.1%) 5/118 (4.2%) 1/85 (1.2%)
    SOMNOLENCE 7/118 (5.9%) 2/118 (1.7%) 1/85 (1.2%)
    Psychiatric disorders
    CONFUSIONAL STATE 9/118 (7.6%) 4/118 (3.4%) 3/85 (3.5%)
    DEPRESSION 3/118 (2.5%) 2/118 (1.7%) 6/85 (7.1%)
    INSOMNIA 4/118 (3.4%) 1/118 (0.8%) 5/85 (5.9%)
    SLEEP DISORDER 6/118 (5.1%) 4/118 (3.4%) 2/85 (2.4%)
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA 7/118 (5.9%) 3/118 (2.5%) 4/85 (4.7%)
    Skin and subcutaneous tissue disorders
    RASH 8/118 (6.8%) 2/118 (1.7%) 0/85 (0%)
    Vascular disorders
    THROMBOSIS 1/118 (0.8%) 0/118 (0%) 5/85 (5.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00154375
    Other Study ID Numbers:
    • CSTI571BDE40
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Apr 26, 2011
    Last Verified:
    Apr 1, 2011