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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00101647




Registration number
NCT00101647
Ethics application status
Date submitted
12/01/2005
Date registered
13/01/2005
Date last updated
15/04/2011

Titles & IDs
Public title
Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia
Scientific title
A Phase II Study of BMS-354825 in Subjects With Accelerated Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Secondary ID [1] 0 0
CA180-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myelogenous Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dasatinib

Experimental: 1 -


Treatment: Drugs: Dasatinib
Tablets, Oral, 70 mg, twice daily, until disease progression or intolerable toxicity, switch to the roll-over study or study closure
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major and Overall Hematologic Response (MaHR and OHR)
Assessment method [1] 0 0
MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Confirmed hematologic response=response confirmed =4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea. Maintaining a response=no 2 consecutive records of nonresponse at assessment. Criteria for CHR and NEL specified in Outcome Measure 2 and criteria for MiHR in Outcome Measure 4.
Timepoint [1] 0 0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
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)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
12 months, 24 months
Secondary outcome [4] 0 0
Median Time in Days From First Dosing Date to Date of MaHR
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Secondary outcome [5] 0 0
Time to OHR
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Secondary outcome [6] 0 0
Best Cytogenetic Response
Assessment method [6] 0 0
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).
Timepoint [6] 0 0
Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment
Secondary outcome [7] 0 0
Best Confirmed Hematologic Response
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Secondary outcome [8] 0 0
Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period
Assessment method [8] 0 0
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 transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).
Timepoint [8] 0 0
Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Secondary outcome [9] 0 0
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations
Assessment method [9] 0 0
Major hematologic and cytogenetic responses (MaHR and MCyR) to dasatinib in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). BCR-ABL=the fused gene found in subjects with this type of CML. Criteria for MaHR are specified in Outcome Measure 2. MCyR=combined complete cytogenetic and partial cytogenetic response rate. Complete Cytogenetic Response= 0% Ph+ Cells in Metaphase in Bone Marrow, Partial Cytogenetic Response \> 0% to 35% Ph+ Cells in Metaphase in Bone Marrow.
Timepoint [9] 0 0
Baseline, at time of disease progression. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Secondary outcome [10] 0 0
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Assessment method [10] 0 0
Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, and functional well-being (PWB, SWB, EWB, FWB). Total score=0 to 108; higher score=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, and FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinically important change.
Timepoint [10] 0 0
Baseline, every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up.(treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Secondary outcome [11] 0 0
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation
Assessment method [11] 0 0
AE=any new untoward medical occurrence or worsening of a pre-existing 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)
Timepoint [11] 0 0
Continuous from pretreatment through each 4-week cycle and at follow-up. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Secondary outcome [12] 0 0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)
Assessment method [12] 0 0
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Timepoint [12] 0 0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Secondary outcome [13] 0 0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 Hours (AUC[0-T])
Assessment method [13] 0 0
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.
Timepoint [13] 0 0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Secondary outcome [14] 0 0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)
Assessment method [14] 0 0
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Timepoint [14] 0 0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Secondary outcome [15] 0 0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)
Assessment method [15] 0 0
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Timepoint [15] 0 0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Secondary outcome [16] 0 0
Population PK of Dasatinib
Assessment method [16] 0 0
Population pharmacokinetic analysis was not done because it is not meaningful for this single study
Timepoint [16] 0 0
Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.

Eligibility
Key inclusion criteria
* Subjects with Philadelphia chromosome positive (PH+) or the fused gene BCR/ABL positive (BCR/ABL+) accelerated phase chronic myeloid leukemia (CML) whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate.
* Subjects must have had prior exposure to imatinib. However, imatinib mesylate does not need to be their most recent CML treatment prior to coming on this study.
* 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 least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 subjects 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 dasatinib (BMS-354825).
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2008
Sample size
Target
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Local Institution - St. Leonards
Recruitment hospital [2] 0 0
Local Institution - South Brisbane
Recruitment hospital [3] 0 0
Local Institution - East Melbourne
Recruitment hospital [4] 0 0
Local Institution - Parkville
Recruitment hospital [5] 0 0
Local Institution - Wien
Recruitment postcode(s) [1] 0 0
- St. Leonards
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- East Melbourne
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment postcode(s) [5] 0 0
- Wien
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
Cordoba
Country [19] 0 0
Belgium
State/province [19] 0 0
B-Leuven
Country [20] 0 0
Belgium
State/province [20] 0 0
Edegem
Country [21] 0 0
Brazil
State/province [21] 0 0
Campinas
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio De Janeiro
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Denmark
State/province [25] 0 0
Aarhus
Country [26] 0 0
Finland
State/province [26] 0 0
Helsinki
Country [27] 0 0
France
State/province [27] 0 0
LIlle
Country [28] 0 0
France
State/province [28] 0 0
Lyon Cedex 03
Country [29] 0 0
France
State/province [29] 0 0
Nantes
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pessac
Country [32] 0 0
France
State/province [32] 0 0
Poitiers Cedex
Country [33] 0 0
France
State/province [33] 0 0
Strasbourg Cedex
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Mainz
Country [36] 0 0
Germany
State/province [36] 0 0
Mannheim
Country [37] 0 0
Israel
State/province [37] 0 0
Ramat-Gan
Country [38] 0 0
Italy
State/province [38] 0 0
Bologna
Country [39] 0 0
Italy
State/province [39] 0 0
Napoli
Country [40] 0 0
Italy
State/province [40] 0 0
Orbassano
Country [41] 0 0
Italy
State/province [41] 0 0
Roma
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Jeollanam-Do
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Kyunggi-Do
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seoul
Country [45] 0 0
Netherlands
State/province [45] 0 0
Nijmegen
Country [46] 0 0
Netherlands
State/province [46] 0 0
Rotterdam
Country [47] 0 0
Norway
State/province [47] 0 0
Trondheim
Country [48] 0 0
Peru
State/province [48] 0 0
Lima
Country [49] 0 0
Philippines
State/province [49] 0 0
Quezon City
Country [50] 0 0
Singapore
State/province [50] 0 0
Singapore
Country [51] 0 0
Sweden
State/province [51] 0 0
Gothenburg
Country [52] 0 0
Sweden
State/province [52] 0 0
Lund
Country [53] 0 0
Sweden
State/province [53] 0 0
Umea
Country [54] 0 0
Sweden
State/province [54] 0 0
Uppsala
Country [55] 0 0
Switzerland
State/province [55] 0 0
Basel
Country [56] 0 0
Taiwan
State/province [56] 0 0
Taipei
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taoyuan
Country [58] 0 0
Thailand
State/province [58] 0 0
Bangkok
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Central
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00101647