Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study

Phase 1CompletedNCT00978731

Bristol-Myers Squibb46 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia

Interventions

DasatinibDRUG

Tablets, Oral, The dosing ranges from 50mg to a total of 240mg daily with the following 3 schedules: * 5 days on, 2 days off * 6 days on, 1 day off * Continuous daily dosing Once Daily (QD) or Twice Daily (BID) dosing, Subjects will be treated until progression of disease despite escalation/reductions of dose to the level deemed safe by available data, until intolerable/unacceptable toxicity or until subject withdrawal from the study or discontinuation of the study

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.

AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled.

Time frame: 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.

Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs.

Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy.

Time frame: 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.

Number of Participants With Grade 3-4 Hematology Abnormalities

Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - \<8.0g/dL, Grade 4: \<6.5g/dL. Platelets: Grade 3: 25.0 - \<50.0\*10\^9/L, Grade 4: \<25.0\*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - \<1.0\*10\^9/L, Grade 4: \<0.5\*10\^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - \<2.0\*10\^9/L, Grade 4: \<1.0\*10\^9/L.

Time frame: 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.

Number of Participants With Grade 3-4 Serum Chemistry Abnormalities

Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 \* ULN (upper limit of normal), Grade 4: \>20.0 \* ULN; Calcium: Grade 3: 6.0-\<7.0 or \>12.5-13.5 mg/dL, Grade 4: \<0.6-\>13.5 mg/dL; Bilirubin: Grade 3: \>3-10 \* ULN, Grade 4: \>10 \* ULN; Creatinine: Grade 3: \>3.0-6.0 \* ULN, Grade 4: \>6.0 \* ULN; Albumin: Grade 3: \<2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-\<0.8 or \>2.46-6.6mEq/L, Grade 4: \<0.6 or \>6.6mEq/L.

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Participants With Complete Hematologic Response (CHR)

CHR should meet all of the following criteria: WBC \<= Institutional ULN; ANC \>= 1000/mm\^3 ; Platelets \< 450 000/mm\^3 , no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood \< 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment.