TriangleNCT00123487 · CITED IN SOURCE DOCUMENTS
Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2014-11-03
This is a phase III study of BMS-354825 in subjects with chronic myelogenous leukemia in accelerated phase, or in myeloid or lymphoid blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia who are resistant or intolerant to imatinib mesylate (Gleevec).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population
Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population
Median Time to Major Hematologic Response (MaHR) - Randomized Population
Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study
Percent of Participants With Overall Hematologic Response - Randomized Population
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population
Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population
Median Progression Free Survival (PFS) - Randomized Population
Median Overall Survival (OS) - Randomized Population
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants
Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants
Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Patients with Philadelphia-Positive (Ph+) (or BCR/ABL+) accelerated phase chronic myeloid leukemia, Ph+ (or BCR/ABL+) blast phase chronic myeloid leukemia, or Ph+ (or BCR/ABL+) acute lymphoblastic leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate * Men and women, 18 years of age or older * Adequate hepatic function * Adequate renal function * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized * Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2 Exclusion Criteria: * Women who are pregnant or breastfeeding * A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy * Uncontrolled or significant cardiovascular disease * Medications that increase bleeding risk * Medications that change heart rhythms * Dementia or altered mental status that would prohibit the understanding or rendering of informed consent * History of significant bleeding disorder unrelated to CML * Concurrent incurable malignancy other than CML * Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy * Prior therapy with BMS-35425 * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 70 mg dasatinib twice a day (BID)
- intervention Names
- Drug: dasatinib
- label
- dasatinib Twice a Day (BID)
- type
- EXPERIMENTAL
- description
- 140 mg dasatinib once a day (QD)
- intervention Names
- Drug: dasatinib
- label
- dasatinib Once a Day (QD)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- dasatinib Once a Day (QD)
- description
- Tablets, Oral, 70 mg BID, indefinitely, survival study
- name
- dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- dasatinib Twice a Day (BID)
- description
- Tablets, Oral, 140 mg QD, indefinitely, survival study
- name
- dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 638
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm\^3; platelets ≥ 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.
- measure
- Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population
- time Frame
- Randomization up to 6 months
- secondary Outcomes
- description
- A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized.
- measure
- Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population
- time Frame
- Randomization up to 2 years
- description
- MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm\^3; platelets ≥ 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants.
- measure
- Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population
- time Frame
- Randomization up to 2 years
- description
- A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months.
- measure
- Median Time to Major Hematologic Response (MaHR) - Randomized Population
- time Frame
- Day 1 up to 6 months (time of primary endpoint), 2 years
- description
- MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Median duration was measured in months.
- measure
- Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study
- time Frame
- Day 1 up to 5 years
- description
- Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. MiHR defined as: \< 15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants.
- measure
- Percent of Participants With Overall Hematologic Response - Randomized Population
- time Frame
- Randomization up to 6 Months, 2 Years
- description
- Type of hematologic response: CHR defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \<100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Minor Hematologic Response (MiHR): \<15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR.
- measure
- Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population
- time Frame
- Randomization up to 6 months, 2 years
- description
- Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants.
- measure
- Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population
- time Frame
- Randomization up to 6 Months, 2 Years
- description
- Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM.
- measure
- Number of Participants With Best Cytogenic Response (CyR) - Randomized Population
- time Frame
- Randomization up to 6 Months, 2 Years
- description
- PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months.
- measure
- Median Progression Free Survival (PFS) - Randomized Population
- time Frame
- Randomization up to 5 Years
- description
- OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months.
- measure
- Median Overall Survival (OS) - Randomized Population
- time Frame
- Randomization up to 5 Years
- description
- PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months.
- measure
- Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population
- time Frame
- 24 months, 36 months, 48 months, 60 months
- description
- With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0.
- measure
- Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants
- time Frame
- Day 1 to Year 7
Full study description
- brief Summary
- This is a phase III study of BMS-354825 in subjects with chronic myelogenous leukemia in accelerated phase, or in myeloid or lymphoid blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia who are resistant or intolerant to imatinib mesylate (Gleevec).
Source references
- references
- citation
- Chu SC, Tang JL, Li CC. Dasatinib in chronic myelogenous leukemia. N Engl J Med. 2006 Sep 7;355(10):1062-3; author reply 1063-4. No abstract available.
- pmid
- 16960978
- type
- RESULT
- citation
- Lilly MB, Ottmann OG, Shah NP, Larson RA, Reiffers JJ, Ehninger G, Muller MC, Charbonnier A, Bullorsky E, Dombret H, Brigid Bradley-Garelik M, Zhu C, Martinelli G. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study. Am J Hematol. 2010 Mar;85(3):164-70. doi: 10.1002/ajh.21615.
- pmid
- 20131302
- type
- DERIVED
- citation
- Kantarjian H, Cortes J, Kim DW, Dorlhiac-Llacer P, Pasquini R, DiPersio J, Muller MC, Radich JP, Khoury HJ, Khoroshko N, Bradley-Garelik MB, Zhu C, Tallman MS. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009 Jun 18;113(25):6322-9. doi: 10.1182/blood-2008-11-186817. Epub 2009 Apr 15.
- pmid
- 19369231
- type
- DERIVED
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Preserved source evidence · Not medical advice