Clinical trial NCT00978731: Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study
Official title: Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Subjects Who Experienced Clinical Benefit on Protocol CA180-002
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-09-17
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002.


Eligibility criteria: This study enrolled participants with Philadelphia chromosome positive (Ph+)chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who had demonstrated hematologic resistance or intolerance to imatinib mesylate (Gleevec) and had experienced clinical benefit (in Investigator's opinion) on protocol CA180002.

Inclusion Criteria:

* Signed written informed consent
* Previous treatment with dasatinib on protocol CA180-002 and receiving clinical benefit in the opinion of the investigator
* Completed a minimum of 3 months on protocol CA180-002
* Eastern Cooperative Oncology Group (ECOG)performance status 0, 1, or 2 (See Appendix 1)
* Prior history of Ph+ chronic, accelerated, or blast phase CML or Ph+ ALL

Exclusion Criteria:

* Women of childbearing potential(WOCBP)who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study
* WOCBP using a prohibited contraceptive method
* Women who are pregnant or breastfeeding
* Met the criteria as defined in protocol CA180-002 for discontinuation of therapy which includes:
* Withdrawal of informed consent (subject's decision to withdraw for any reason)
* Any clinical adverse event, laboratory abnormality or intercurrent illness which, in the opinion of the investigator, indicates that continued treatment with dasatinib is not in the best interest of the subject
* Imprisonment or the compulsory detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Medical History and Concurrent Diseases

* A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy;
* Uncontrolled angina within 3 months
* 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
* Dementia or altered mental status that would prohibit the understanding or rendering of informed consent;
* History of significant bleeding disorder unrelated to CML, including:

  1. Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  2. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

Physical and Laboratory Test Findings

* Total bilirubin ≥ 1.5 mg/dl
* alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the institutional upper limits of normal
* Serum creatinine ≥ 1.5 times the institutional upper limits of normal

Prohibited Therapies and/or Medications

* Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:

  * quinidine, procainamide, disopyramide
  * amiodarone, sotalol, ibutilide, dofetilide
  * erythromycins, clarithromycin
  * chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
  * cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
* Medications that inhibit platelet function and any non-steroidal anti-inflammatory drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to CML are eligible for this protocol

Primary outcomes:
measure: Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.
timeFrame: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs.
timeFrame: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants With Grade 3-4 Hematology Abnormalities
timeFrame: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants With Grade 3-4 Serum Chemistry Abnormalities
timeFrame: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants With Dose Interruptions and Dose Reductions
timeFrame: From start of study to final assessment (up to 32.2 months).
Secondary outcomes:
measure: Number of Participants With Complete Hematologic Response (CHR)
timeFrame: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Median Number of Months of CHR (Kaplan Meier Method)
timeFrame: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants With Major Cytogenetic Response (MCyR)
timeFrame: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Median Number of Months of Major Cytogenetic Response (MCyR)
timeFrame: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Number of Participants With Best Cytogenetic Response
timeFrame: Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method)
timeFrame: Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
measure: Median Number of Months of Overall Survival (OS) (Kaplan Meier Method)
timeFrame: Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: