Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Chronic Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00101595
• Other study ID #: CA180-015
• Status: Completed
• Phase: Phase 2
• First received: January 12, 2005
• Last updated: April 7, 2011
• Start date: January 2005
• Est. completion date: December 2007

Study information

• Verified date: April 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00110097

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Blast Crisis
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoblastic, Acute, Philadelphia-positive
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Dasatinib
Tablets, Oral, 70 mg, twice daily, Until disease progression or untolerable toxicity, switch to the roll-over study or study closure

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Cordoba
Australia	Local Institution	St. Leonards	New South Wales
Austria	Local Institution	Wien
Belgium	Local Institution	B-Leuven
Belgium	Local Institution	Edegem
Belgium	Local Institution	Yvoir
Brazil	Local Institution	Campinas
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Toronto	Ontario
Denmark	Local Institution	Aarhus
Finland	Local Institution	Helsinki
France	Local Institution	Lille
France	Local Institution	Lyon Cedex 03
France	Local Institution	Nantes
France	Local Institution	Paris
France	Local Institution	Pessac
France	Local Institution	Poitiers Cedex
France	Local Institution	Strasbourg Cedex
Germany	Local Institution	Frankfurt/Main
Germany	Local Institution	Hamburg
Germany	Local Institution	Mainz
Germany	Local Institution	Mannheim
Israel	Local Institution	Ramat-Gan
Italy	Local Institution	Bologna
Italy	Local Institution	Orbassano
Italy	Local Institution	Roma
Korea, Republic of	Local Institution	Kyunggi-Do
Korea, Republic of	Local Institution	Seoul
Netherlands	Local Institution	Nijmegen
Netherlands	Local Institution	Rotterdam
Norway	Local Institution	Trondheim
Peru	Local Institution	Lima
Sweden	Local Institution	Gothenburg
Sweden	Local Institution	Lund
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Umea
Sweden	Local Institution	Uppsala
Switzerland	Local Institution	Basel
United Kingdom	Local Institution	Glasgow	Central
United Kingdom	Local Institution	London	Greater London
United States	Local Institution	Anaheim	California
United States	Local Institution	Atlanta	Georgia
United States	Local Institution	Birmingham	Alabama
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Hackensack	New Jersey
United States	Local Institution	Houston	Texas
United States	Local Institution	Jacksonville	Florida
United States	Local Institution	Kansas City	Kansas
United States	Local Institution	Los Angeles	California
United States	Local Institution	Nashville	Tennessee
United States	Local Institution	New York	New York
United States	Local Institution	Pittsburgh	Pennsylvania
United States	Local Institution	Portland	Oregon
United States	Local Institution	St. Louis	Missouri
United States	Local Institution	Stanford	California
United States	Local Institution	Tampa	Florida
United States	Local Institution	Vallejo	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Peru,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (3)

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. Epub 2006 Dec 21. — View 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. Epub 2007 May 11. — View Citation

Porkka K, Koskenvesa P, Lundán T, Rimpiläinen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Höglund 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major and overall hematologic response rates		throughout the study	No
Secondary	Durability of hematologic response and time to hematologic response (major and overall)		throughout the study	No
Secondary	Assess cytogenetic and molecular responses		throughout the study	No
Secondary	Measure minor hematologic response rate in the imatinib resistant group		throughout the study	No
Secondary	Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene		throughout the study	No
Secondary	Measure the heath-related QOL using FACT-G		throughout the study	No
Secondary	To assess safety and tolerability of dasatinib		throughout the study	Yes
Secondary	Population PK		first month	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm