Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study

NCT00978731 | Completed Phase 1 Results

• 1 other identifier: CA180-039
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Leukemia

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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 Dose Interruptions and Dose Reductions

  Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times.

  From start of study to final assessment (up to 32.2 months).

Secondary Outcomes (7)

• Number of Participants With Complete Hematologic Response (CHR)

  Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

• Median Number of Months of CHR (Kaplan Meier Method)

  Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

• Number of Participants With Major Cytogenetic Response (MCyR)

  Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

• Median Number of Months of Major Cytogenetic Response (MCyR)

  Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

• Number of Participants With Best Cytogenetic Response

  Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Study Arms (1)

Dasatinib

EXPERIMENTAL

Drug: Dasatinib

Interventions

Dasatinib DRUG

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

Also known as: BMS-354825, Sprycel, Src Kinase

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

MeSH Terms

Conditions

Leukemia

Interventions

Dasatinib; src-Family Kinases

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 16, 2009
• First Posted: September 17, 2009
• Study Start: December 1, 2005
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: April 28, 2011
• Results First Posted: April 19, 2011

Record last verified: 2011-04