Clinical trial NCT00101647: Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia
Official title: A Phase II Study of BMS-354825 in Subjects With Accelerated Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myelogenous Leukemia
Keywords: Chronic myelogenous leukemia (CML): Accelerated phase
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-01-13
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Major and Overall Hematologic Response (MaHR and OHR)
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Secondary outcomes:
measure: Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)
timeFrame: 12 months
measure: 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)
timeFrame: 24 months
measure: Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months
timeFrame: 12 months, 24 months
measure: Median Time in Days From First Dosing Date to Date of MaHR
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
measure: Time to OHR
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
measure: Best Cytogenetic Response
timeFrame: Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment
measure: Best Confirmed Hematologic Response
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
measure: Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period
timeFrame: Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
measure: MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations
timeFrame: Baseline, at time of disease progression. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
measure: Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
timeFrame: 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).
measure: Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation
timeFrame: 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).
measure: Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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.
measure: 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])
timeFrame: 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.
measure: Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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.
measure: Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)
timeFrame: 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.
measure: Population PK of Dasatinib
timeFrame: Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution
state: Alabama
city: Anaheim
country: United States
facility: Local Institution
state: California
city: Los Angeles
country: United States
facility: Local Institution
state: California
city: Stanford
country: United States
facility: Local Institution
state: California
city: Vallejo
country: United States
facility: Local Institution
state: California
city: Jacksonville
country: United States
facility: Local Institution
state: Florida
city: Tampa
country: United States
facility: Local Institution
state: Florida
city: Atlanta
country: United States
facility: Local Institution
state: Georgia
city: Chicago
country: United States
facility: Local Institution
state: Illinois
city: Kansas City
country: United States
facility: Local Institution
state: Kansas
city: Baltimore
country: United States
facility: Local Institution
state: Maryland
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution
state: Michigan
city: St. Louis
country: United States
facility: Local Institution
state: Missouri
city: Hackensack
country: United States
facility: Local Institution
state: New Jersey
city: New York
country: United States
facility: Local Institution
state: New York
city: Portland
country: United States
facility: Local Institution
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution
state: Tennessee
city: Dallas
country: United States
facility: Local Institution
state: Texas
city: Houston
country: United States
facility: Local Institution
state: Texas
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: St. Leonards
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: East Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Wien
country: Australia
facility: Local Institution
city: B-Leuven
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Campinas
country: Brazil
facility: Local Institution
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Aarhus
country: Denmark
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: LIlle
country: France
facility: Local Institution
city: Lyon Cedex 03
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Poitiers Cedex
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Ramat-Gan
country: Israel
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Orbassano
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Jeollanam-Do
country: Korea, Republic of
facility: Local Institution
city: Kyunggi-Do
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Nijmegen
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Gothenburg
country: Sweden
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Umea
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Basel
country: Switzerland
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Central
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Guilhot F, Apperley J, Kim DW, Bullorsky EO, Baccarani M, Roboz GJ, Amadori S, de Souza CA, Lipton JH, Hochhaus A, Heim D, Larson RA, Branford S, Muller MC, Agarwal P, Gollerkeri A, Talpaz M. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007 May 15;109(10):4143-50. doi: 10.1182/blood-2006-09-046839. Epub 2007 Jan 30.
citation: Apperley JF, Cortes JE, Kim DW, Roy L, Roboz GJ, Rosti G, Bullorsky EO, Abruzzese E, Hochhaus A, Heim D, de Souza CA, Larson RA, Lipton JH, Khoury HJ, Kim HJ, Sillaber C, Hughes TP, Erben P, Van Tornout J, Stone RM. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol. 2009 Jul 20;27(21):3472-9. doi: 10.1200/JCO.2007.14.3339. Epub 2009 Jun 1.