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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00101595
• Collaborator: (none)
• Enrollment: 96
• Locations: 60
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia; Leukemia, Lymphoblastic, Acute, Philadelphia-positive	Drug: Dasatinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2005
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Dasatinib; Tablets, Oral, 70 mg, twice daily, Until disease progression or untolerable toxicity, switch to the roll-over study or study closure; Other Names: BMS-354825 Sprycel

Outcome Measures

Primary Outcome Measures

1. Major and overall hematologic response rates [throughout the study]

Secondary Outcome Measures

1. Durability of hematologic response and time to hematologic response (major and overall) [throughout the study]

2. Assess cytogenetic and molecular responses [throughout the study]

3. Measure minor hematologic response rate in the imatinib resistant group [throughout the study]

4. Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene [throughout the study]

5. Measure the heath-related QOL using FACT-G [throughout the study]

6. To assess safety and tolerability of dasatinib [throughout the study]

7. Population PK [first month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Birmingham	Alabama	United States
2	Local Institution	Anaheim	California	United States
3	Local Institution	Los Angeles	California	United States
4	Local Institution	Stanford	California	United States
5	Local Institution	Vallejo	California	United States
6	Local Institution	Jacksonville	Florida	United States
7	Local Institution	Tampa	Florida	United States
8	Local Institution	Atlanta	Georgia	United States
9	Local Institution	Chicago	Illinois	United States
10	Local Institution	Kansas City	Kansas	United States
11	Local Institution	Boston	Massachusetts	United States
12	Local Institution	St. Louis	Missouri	United States
13	Local Institution	Hackensack	New Jersey	United States
14	Local Institution	New York	New York	United States
15	Local Institution	Portland	Oregon	United States
16	Local Institution	Pittsburgh	Pennsylvania	United States
17	Local Institution	Nashville	Tennessee	United States
18	Local Institution	Houston	Texas	United States
19	Local Institution	Buenos Aires		Argentina
20	Local Institution	Cordoba		Argentina
21	Local Institution	St. Leonards	New South Wales	Australia
22	Local Institution	Wien		Austria
23	Local Institution	B-Leuven		Belgium
24	Local Institution	Edegem		Belgium
25	Local Institution	Yvoir		Belgium
26	Local Institution	Campinas		Brazil
27	Local Institution	Sao Paulo		Brazil
28	Local Institution	Toronto	Ontario	Canada
29	Local Institution	Montreal	Quebec	Canada
30	Local Institution	Aarhus		Denmark
31	Local Institution	Helsinki		Finland
32	Local Institution	Lille		France
33	Local Institution	Lyon Cedex 03		France
34	Local Institution	Nantes		France
35	Local Institution	Paris		France
36	Local Institution	Pessac		France
37	Local Institution	Poitiers Cedex		France
38	Local Institution	Strasbourg Cedex		France
39	Local Institution	Frankfurt/Main		Germany
40	Local Institution	Hamburg		Germany
41	Local Institution	Mainz		Germany
42	Local Institution	Mannheim		Germany
43	Local Institution	Ramat-Gan		Israel
44	Local Institution	Bologna		Italy
45	Local Institution	Orbassano		Italy
46	Local Institution	Roma		Italy
47	Local Institution	Kyunggi-Do		Korea, Republic of
48	Local Institution	Seoul		Korea, Republic of
49	Local Institution	Nijmegen		Netherlands
50	Local Institution	Rotterdam		Netherlands
51	Local Institution	Trondheim		Norway
52	Local Institution	Lima		Peru
53	Local Institution	Gothenburg		Sweden
54	Local Institution	Lund		Sweden
55	Local Institution	Stockholm		Sweden
56	Local Institution	Umea		Sweden
57	Local Institution	Uppsala		Sweden
58	Local Institution	Basel		Switzerland
59	Local Institution	Glasgow	Central	United Kingdom
60	Local Institution	London	Greater London	United Kingdom

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• ClinicalTrials.gov Identifier: NCT00101595
• Other Study ID Numbers: CA180-015; NCT00110097
• First Posted: Jan 13, 2005
• Last Update Posted: Apr 14, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Lymphoid blast phase chronic myeloid leukemia; Philadelphia chromosome positive acute lymphoblastic leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Philadelphia Chromosome; Dasatinib

Study Results

No Results Posted as of Apr 14, 2011