Clinical Trial: Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase II Study of BMS-354825 in Subjects With Accelerated Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Brief Summary: The purpose of this clinical research study is to learn if BMS-354825 will have activity, defined by hematologic response, in subjects who have accelerated phase chronic myeloid leukemia (CML) who are resistant to or intolerant to imatinib mesylate. The safety of this treatment will also be studied.
Detailed Summary:
Sponsor: Bristol-Myers Squibb
Current Primary Outcome: Major and Overall Hematologic Response (MaHR and OHR) [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]
Original Primary Outcome:
Current Secondary Outcome:
- Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response) [ Time Frame: 12 months ]MaHR=best response of CHR or NEL. CHR=white blood cells ≤institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤iULN; no extramedullary involvement; at least 1 of: ANC ≥500/mm3 & <1000/mm3; platelets ≥20,000/mm3 & <100,000/mm3.
- Percentage of Participants Who Achieved MaHR and Did Not Progress at 24 Months in the Imatinib-Resistant Group (Based on the Kaplan-Meier Estimate of the Duration of Response) [ Time Frame: 24 months ]Percentage of participants in the Imatinib-Resistant Group who achieved MaHR and did not progress at Month 24, based on the Kaplan-Meier estimate of the duration of response. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR and NEL are specified in Outcome Measure 2.
- Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months [ Time Frame: 12 months, 24 months ]Percentage of participants who achieved OHR and did not progress at specified timepoints, based on the Kaplan-Meier estimate of the duration of response. OHR=best confirmed response of MaHR or MiHR. MaHR criteria in Outcome Measure 2. MiHR= <15% blasts in bone marrow and <15% blasts in peripheral blood (PB); <30% blasts+promyelocytes in bone marrow and <30% blasts+promyelocytes in PB; <20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response= confirmed ≥4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.
- Median Time in Days From First Dosing Date to Date of MaHR [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]MaHR=best response of CHR or NEL. CHR=white blood cells ≤institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤iULN; no extramedullary involvement; at least 1 of: ANC ≥500/mm3 & <1000/mm3; platelets ≥20,000/mm3 & <100,000/mm3.
- Time to OHR [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]Median time (in months) from first dosing date to date of OHR. OHR=best confirmed response of MaHR or MiHR. Criteria for MaHR specified in Outcome Measure 2. MiHR= <15% blasts in bone marrow and <15% blasts in peripheral blood (PB); <30% blasts+promyelocytes in bone marrow and <30% blasts+promyelocytes in PB; <20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response = response confirmed ≥4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.
- Best Cytogenetic Response [ Time Frame: Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment ]Number of participants with complete, partial, minor, minimal, or no cytogenetic response. Determination of cytogenetic response based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).
- Best Confirmed Hematologic Response [ Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment ]Number of participants with confirmed complete hematologic response (CHR) or No Evidence of Leukemia (NEL), minor hematologic response (MiHR), or no hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for CHR and NEL are specified in Outcome Measure 2; criteria for MiHR are specified in Outcome Measure 4.
- Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period [ Time Frame: Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria). ]Number of participants who achieved an MMR at any time during the treatment period. MMR was calculated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse tr
Original Secondary Outcome:
Information By: Bristol-Myers Squibb
Dates:
Date Received: January 12, 2005
Date Started: December 2004
Date Completion:
Last Updated: April 13, 2011
Last Verified: April 2011
