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Completed

NCT Number: NCT00101660

Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib

The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.

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Key information

Conditions

Chronic Myeloid Leukemia Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Philadelphia-Positive Myeloid Leukemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution, St Leonards, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age of 18 years and older.
  • Chronic myeloid leukemia (CML)
  • Previous treatment with imatinib at a dose of >600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
  • CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
  • Intolerance to imatinib at any dose
  • Adequate organ function
  • Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.

Exclusion criteria

  • Woman who are pregnant or breastfeeding
  • Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above
  • Previous diagnosis of accelerated phase or blast crisis CML.
  • Participants who are eligible and willing to undergo transplantation during the screening period
  • Uncontrolled or significant cardiovascular disease
  • Use of imatinib within 7 days.
  • Use of interferon or cytarabine within 14 days
  • Use of a targeted small-molecule anticancer agent within 14 days
  • Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
  • Prior therapy with dasatinib.

Treatment and study plan

dasatinib

Drug

Tablets; oral; 70 mg BID, depending on response

Primary outcomes

  1. Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)

    Time frame: 2 years

    Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.

Secondary outcomes

  1. Number of Imatinib-intolerant Participants With MCyR

    Time frame: Baseline to 2 years

    Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.

  2. Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months

    Time frame: 12 and 24 Months

    Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.

  3. Median Time From First Dosing Date to Date of MCyR

    Time frame: Baseline (within 4 weeks of Day 1) and every 12 weeks

    MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.

  4. Number of Participants With Complete Hematologic Response (CHR)

    Time frame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study

    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

  5. Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months

    Time frame: 12 and 24 months

    Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

  6. Median Time From First Dosing Until CHR

    Time frame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study

    CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.

  7. Number of Participants With Major Molecular Response (MMR)

    Time frame: Baseline to 2 years

    MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor.

  8. Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores

    Time frame: Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.

    Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.

  9. Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE

    Time frame: Continuously, from baseline through 2 years

    AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

  10. Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE

    Time frame: Continuously, from baseline through 2 years

    AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

  11. Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib

    Time frame: Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.

    Blood samples were collected for PK to be included in separate population PK analyses.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib

Important dates

Study start
2005
Primary completion
2006
Study completion
2008
First posted
Jan 13, 2005
Registry last updated
Mar 2, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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