TriangleNCT00123474 · CITED IN SOURCE DOCUMENTS
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
- 2016-08-25
This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia chromosome or BCR-ABL positive chronic myelogenous 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 Cytogenetic Response (MCyR) at 6 Months Follow-Up
Percent of Participants With MCyR At or Prior to 24 Months Follow-Up
Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up
Time to MCyR in Participants With MCyR at 6 Months Follow-Up
Time to CHR in Participants With CHR at 6 Months Follow-Up
Time to MCyR in Participants With MCyR at 24 Months Follow-Up
Time to CHR in Participants With CHR At 24 Months Follow-Up
Number of Participants With MCyR Whose Disease Progressed by 24 Months
Number of Participants With CHR Whose Disease Progressed by 24 Months
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose
Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 6 Months Follow-Up
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 24 Months Follow-Up
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up
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: * Subjects with Philadelphia chromosome positive (Ph+) (or BCR/ABL+) chronic phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate. * Men and women, 18 years 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. Exclusion Criteria: * Women who are pregnant or breastfeeding * Subjects who are eligible and willing to undergo transplantation during the screening period * 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 * 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
- maximum Age
- 90 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: dasatinib
- label
- 1
- type
- EXPERIMENTAL
- intervention Names
- Drug: dasatinib
- label
- 2
- type
- EXPERIMENTAL
- intervention Names
- Drug: dasatinib
- label
- 3
- type
- EXPERIMENTAL
- intervention Names
- Drug: dasatinib
- label
- 4
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- 1
- description
- Tablets, Oral, 50 mg BID, indefinitely, survival study
- name
- dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- 2
- description
- Tablets, Oral, 70 mg BID, indefinitely, survival study
- name
- dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- 3
- description
- Tablets, Oral, 100 mg QD, indefinitely, survival study
- name
- dasatinib
- other Names
- Sprycel
- BMS-354825
- type
- DRUG
- arm Group Labels
- 4
- 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
- 724
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Cytogenetic response (CyR) was based on the number of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.
- measure
- Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up
- time Frame
- 6 months
- secondary Outcomes
- description
- CyR was based on the number of Ph+ metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: CCyR: 0% Ph+ cells in metaphase in BM; PCyR: \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR. Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.
- measure
- Percent of Participants With MCyR At or Prior to 24 Months Follow-Up
- time Frame
- 24 months
- description
- A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \< 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); \< 5% myelocytes plus metamyelocytes in PB; Basophils in PB \< 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.
- measure
- Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up
- time Frame
- 6 months, 24 months
- description
- Time to MCyR was defined as the time from the first dosing date until criteria were first met for CCyR or PCyR, whichever occurred first. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to MCyR response for responders and time to last cytogenetic assessment for non-responders).
- measure
- Time to MCyR in Participants With MCyR at 6 Months Follow-Up
- time Frame
- 6 months
- description
- Time to CHR was defined as the time from the first dosing date until criteria are first met for the response. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to CHR response for responders and time to last hematologic assessment for non-responders).
- measure
- Time to CHR in Participants With CHR at 6 Months Follow-Up
- time Frame
- 6 months
- description
- Time to MCyR was defined as the time from the first dosing date until criteria were first met for CCyR or PCyR, whichever occurred first. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to MCyR response for responders and time to last cytogenetic assessment for non-responders). Cytogenetic assessments were not done after the 2 Year Follow-up.
- measure
- Time to MCyR in Participants With MCyR at 24 Months Follow-Up
- time Frame
- 24 months
- description
- Time to CHR was defined as the time from the first dosing date until criteria are first met for the response. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to CHR response for responders and time to last hematologic assessment for non-responders). Cytogenetic assessments were not done after the 2 Year Follow-up.
- measure
- Time to CHR in Participants With CHR At 24 Months Follow-Up
- time Frame
- 24 months
- description
- Progression in a participant=participant achieved a CHR and no longer met the criteria consistently over consecutive 2-weeks after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to \>20,000/mm\^3 or an increase by \> 50,000/mm\^3 on two assessments performed at least 2 weeks apart; participant met criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a ≥ 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of MCyR, medium duration of MCyR could not be estimated because the majority of participants with MCyR continued to respond, or could not be reliably estimated because of the large number of censored participants. Cytogenetic assessments were not done after the 24 month follow-up.
- measure
- Number of Participants With MCyR Whose Disease Progressed by 24 Months
- time Frame
- 24 months
- description
- Progression in a participant=achieved a CHR and subsequently no longer met the criteria consistently over a consecutive 2-week period after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to \>20,000/mm\^3 or an increase by \> 50,000/mm\^3 on two assessments performed at least 2 weeks apart; met the criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a ≥ 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of CHR, medium duration of CHR could not be estimated because the majority of participants with CHR continued to respond, or could not be reliably estimated because of the large number of censored participants.
- measure
- Number of Participants With CHR Whose Disease Progressed by 24 Months
- time Frame
- 24 months
- description
- BCR-ABL mutations were assessed in participants prior to the start of study drug (baseline) and at the time of disease progression or at end of therapy. Quantification of BCR-ABL transcripts in peripheral blood was evaluated using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR, RT-PCR).
- measure
- Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants
- time Frame
- Baseline up to 24 months
- description
- PFS= time from randomization until: CHR achieved and participant subsequently no longer met criteria for CHR over 2 weeks; no CHR after receiving maximum dose and an increase in WBC (ie, doubling of the count from the lowest value to \> 20,000/mm\^3 or an increase by \> 50,000/mm\^3 on 2 assessments performed 2 weeks apart); participant met criteria of accelerated phase or blast phase CML; participant had MCyR and subsequently no longer met criteria for MCyR after starting maximum dose; participant had a ≥ 30% absolute increase in number of Ph+ metaphases. Deaths without a reported prior progression were considered to have progressed on the date of death; those who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. When first progression reported during follow-up, it was censored at last on-study assessment. If the first progression reported during follow-up was death, participant considered to have progressed at date of death.
- measure
- Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
- time Frame
- 24, 36, 48, 60, 72, and 84 months
- description
- Overall survival (OS) was defined as the time from randomization until death. Survival data were collected for up to 5 years on participants who had discontinued dasatinib treatment. Participants who did not die or who were lost to follow-up were censored on the last date the participant was known to be alive.
- measure
- Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
- time Frame
- 24, 36, 48, 60, 72, and 84 months
- description
- 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; PCyR: \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR.
- measure
- Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose
- time Frame
- 6 months, 24 months
Full study description
- brief Summary
- This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia chromosome or BCR-ABL positive chronic myelogenous leukemia, who are resistant or intolerant to imatinib mesylate (Gleevec).
Source references
- references
- citation
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- 19924787
- type
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- citation
- Muller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24.
- pmid
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- citation
- Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12. doi: 10.1200/JCO.2007.14.9260. Epub 2008 Jun 9.
- pmid
- 18541900
- type
- BACKGROUND
- citation
- Shah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J, Mohamed H, Healey D, Kantarjian H, Hochhaus A, Saglio G. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016 Sep;91(9):869-74. doi: 10.1002/ajh.24423. Epub 2016 Jun 20.
- pmid
- 27192969
- type
- DERIVED
- citation
- Shah NP, Guilhot F, Cortes JE, Schiffer CA, le Coutre P, Brummendorf TH, Kantarjian HM, Hochhaus A, Rousselot P, Mohamed H, Healey D, Cunningham M, Saglio G. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014 Apr 10;123(15):2317-24. doi: 10.1182/blood-2013-10-532341. Epub 2014 Feb 25.
- pmid
- 24569263
- type
- DERIVED
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Preserved source evidence · Not medical advice