Clinical trial NCT00101660: Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib
Official title: A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Philadelphia-Positive Myeloid Leukemia
Keywords: Chronic phase Philadelphia chromosome chronic myeloid leukemia (Ph+CML)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-01-13
Enrollment: 387
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 assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.


Eligibility criteria: Inclusion Criteria:

* Age of 18 years and older.
* Chronic myeloid leukemia (CML)
* Previous treatment with imatinib at a dose of \>600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
* CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
* Intolerance to imatinib at any dose
* Adequate organ function
* Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.

Exclusion Criteria:

* Woman who are pregnant or breastfeeding
* Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above
* Previous diagnosis of accelerated phase or blast crisis CML.
* Participants who are eligible and willing to undergo transplantation during the screening period
* Uncontrolled or significant cardiovascular disease
* Use of imatinib within 7 days.
* Use of interferon or cytarabine within 14 days
* Use of a targeted small-molecule anticancer agent within 14 days
* Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
* Prior therapy with dasatinib.

Primary outcomes:
measure: Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)
timeFrame: 2 years
Secondary outcomes:
measure: Number of Imatinib-intolerant Participants With MCyR
timeFrame: Baseline to 2 years
measure: Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months
timeFrame: 12 and 24 Months
measure: Median Time From First Dosing Date to Date of MCyR
timeFrame: Baseline (within 4 weeks of Day 1) and every 12 weeks
measure: Number of Participants With Complete Hematologic Response (CHR)
timeFrame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
measure: Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months
timeFrame: 12 and 24 months
measure: Median Time From First Dosing Until CHR
timeFrame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
measure: Number of Participants With Major Molecular Response (MMR)
timeFrame: Baseline to 2 years
measure: Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
timeFrame: Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.
measure: Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE
timeFrame: Continuously, from baseline through 2 years
measure: Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE
timeFrame: Continuously, from baseline through 2 years
measure: Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
timeFrame: Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Local Institution
state: California
city: Loma Linda
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: Hartford
country: United States
facility: Local Institution
state: Connecticut
city: Washington
country: United States
facility: Local Institution
state: District of Columbia
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: Indianapolis
country: United States
facility: Local Institution
state: Indiana
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: Kansas City
country: United States
facility: Local Institution
state: Missouri
city: St. Louis
country: United States
facility: Local Institution
state: Missouri
city: Omaha
country: United States
facility: Local Institution
state: Nebraska
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: Philadelphia
country: United States
facility: Local Institution
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution
state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution
state: South Carolina
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: San Antonio
country: United States
facility: Local Institution
state: Texas
city: Tyler
country: United States
facility: Local Institution
state: Texas
city: Spokane
country: United States
facility: Local Institution
state: Washington
city: St. Leonards
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: East Mebourne
country: Australia
facility: Local Institution
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Wein
country: Austria
facility: Local Institution
city: B-Leuven
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Yvoir
country: Belgium
facility: Local Institution
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
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 Cedex
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: Leipzig
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Co Galway
country: Ireland
facility: Local Institution
state: Galway
city: Dublin
country: Ireland
facility: Local Institution
city: Ramat-Gan
country: Israel
facility: Local Institution
city: Bari
country: Italy
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Milano
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: Kyunggi-Do
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: Singapore
country: Singapore
facility: Local Institution
city: Parktown
country: South Africa
facility: Local Institution
state: Gauteng
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Gothenburg
country: Sweden
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Stockholm
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 Instituion
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: Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007 Mar 15;109(6):2303-9. doi: 10.1182/blood-2006-09-047266. Epub 2006 Nov 30.
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.