Clinical trial NCT00101595: Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Official title: A Phase II Study of BMS-354825 in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Resistant to or Intolerant of Imatinib Mesylate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Leukemia, Lymphoblastic, Acute, Philadelphia-positive
Keywords: Lymphoid blast phase chronic myeloid leukemia
Philadelphia chromosome positive acute lymphoblastic leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-01-13
Enrollment: 96
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 as defined by hematologic responses in subjects with lymphoid blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia with primary or acquired resistance to imatinib mesylate.


Eligibility criteria: Inclusion Criteria:

* Subjects with Philadelphia chromosome positive (Ph+) (BCR/ABL+) lymphoid blast phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate.
* Subjects who are considered to have lymphoid blast phase CML if they meet at least one of the following criteria: \*30% lymphoid blasts in peripheral blood or bone marrow. \*Extramedullary infiltrates of leukemic cells (other than in spleen or liver) with peripheral blood lymphoid blast morphology.
* ECOG performance status score 0-2.
* Adequate hepatic function defined as: \*Total bilirubin less than or equal to 2.0 times the institutional upper limit of normal; \*alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the institutional upper limit of normal.
* Adequate renal function defined as: \*serum creatinine less than or equal to 1.5 times the institutional upper normal limit.
* Men and women, 18 years of age or older.
* 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. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IC/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

Exclusion Criteria:

* WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least 1 month before and for at least 3 months after completion of the study medication.
* WOCBP using a prohibited contraceptive method (not applicable).
* Women who are pregnant or breastfeeding.
* Women with a positive pregnancy test on enrollment or prior to study drug administration.
* Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication.
* 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.
* Demential 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.
* Subjects who received any of the following:

  * imatinib mesylate within 7 days;
  * interferon or cytarabine within 14 days;
  * a targeted small molecule anti-cancer agent within 14 days;
  * any other investigational or antineoplastic agent other than hydroxyurea or anagrelide within 28 days before starting treatment with BMS-354825.
* Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes.
* Subjects taking medications that irreversibly inhibit platelet function.
* Prior therapy with 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 rates
timeFrame: throughout the study
Secondary outcomes:
measure: Durability of hematologic response and time to hematologic response (major and overall)
timeFrame: throughout the study
measure: Assess cytogenetic and molecular responses
timeFrame: throughout the study
measure: Measure minor hematologic response rate in the imatinib resistant group
timeFrame: throughout the study
measure: Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene
timeFrame: throughout the study
measure: Measure the heath-related QOL using FACT-G
timeFrame: throughout the study
measure: To assess safety and tolerability of dasatinib
timeFrame: throughout the study
measure: Population PK
timeFrame: first month
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: Boston
country: United States
facility: Local Institution
state: Massachusetts
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: 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: Wien
country: Austria
facility: Local Institution
city: B-Leuven
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Yvoir
country: Belgium
facility: Local Institution
city: Campinas
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
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
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: Frankfurt/Main
country: Germany
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: Orbassano
country: Italy
facility: Local Institution
city: Roma
country: Italy
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: 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 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: Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, Rege-Cambrin G, Radich J, Hochhaus A, Apanovitch AM, Gollerkeri A, Coutre S. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007 Oct 1;110(7):2309-15. doi: 10.1182/blood-2007-02-073528. Epub 2007 May 11.
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.