Clinical trial NCT00101816: Dasatinib (BMS-354825) in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Official title: A Phase II Study of BMS-354825 in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Blast Crisis
Keywords: Myeloid blast phase Chronic Myeloid Leukemia (CML)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-01-14
Enrollment: 124
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 study is to see what effect an investigational drug (BMS-354825) has on subjects who are currently in the myeloid blast phase of chronic myeloid leukemia (CML) and who are either resistant to or intolerant of imatinib mesylate. Another purpose of the study is to see what side effects this drug may have on subjects.


Eligibility criteria: Inclusion Criteria:

* Subjects with myeloid blast phase chronic myeloid leukemia
* Subjects who are either resistant or intolerant of imatinib mesylate

Exclusion Criteria:

* Subjects who are eligible and willing to undergo transplantation
* Serious uncontrolled medical disorder or active infection
* Uncontrolled or significant heart problems, such as congestive heart failure, recent heart attack, etc
* Subjects receiving medications that may affect heart rhythm
* Other malignancy/cancer other than CML
* History of significant bleeding disorder unrelated to CML
* Pregnant or breastfeeding women (subjects must avoid becoming pregnant)
* Subjects received imatinib within 7 days, interferon or cytarabine within 14 days, a targeted anticancer medication within 14 days, an antineoplastic agent (other than hydroxyurea or anagrelide) within 28 days, or any other investigation medication in 28 days
* Subject is receiving medications that affect platelet function or an anticoagulant

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 Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
Secondary outcomes:
measure: Median Duration of Major Hematologic Response (MaHR)
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
measure: Median Duration of Overall Hematologic Response (OHR)
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
measure: Time to MaHR and OHR
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
measure: Number of Participants With Complete, Partial, Minor, Minimal, or No 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: Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
timeFrame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatment
measure: Number of Participants Achieving Major Molecular Response (MMR)
timeFrame: Baseline, every 12 weeks, and at time of Complete Cytogenetic Response (CCyR) for quantitative Polyermase Chain Reaction (qPCR) analysis
measure: MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
timeFrame: baseline, at time of disease progression
measure: Minimally Significant Changes 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
measure: Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
timeFrame: Continuously throughout study, from pre-treatment visit through end of study (due to death, unacceptable toxicity, treatment failure, etc) and follow-up period
measure: Pharmacokinetics (PK) of Dasatinib - 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 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h or 24 h(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 - 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 - 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: Pharmacokinetics (PK) of Dasatinib's 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's 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 h (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's 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: Denver
country: United States
facility: Local Institution
state: Colorado
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 Brunswick
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: Houston
country: United States
facility: Local Institution
state: Texas
city: Seattle
country: United States
facility: Local Institution
state: Washington
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Wien
country: Austria
facility: Local Institution
city: B-Leuven
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
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 Cedex 10
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: 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: 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: Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P, Branford S, Agarwal P, Gollerkeri A, Baccarani M. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007 Apr 15;109(8):3207-13. doi: 10.1182/blood-2006-09-046888. Epub 2006 Dec 21.
citation: Porkka K, Koskenvesa P, Lundan T, Rimpilainen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Hoglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FY. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008 Aug 15;112(4):1005-12. doi: 10.1182/blood-2008-02-140665. Epub 2008 May 13.