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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00101595




Registration number
NCT00101595
Ethics application status
Date submitted
12/01/2005
Date registered
13/01/2005
Date last updated
14/04/2011

Titles & IDs
Public title
Dasatinib (BMS-354825) in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Scientific 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
Secondary ID [1] 0 0
CA180-015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 0 0
Leukemia, Lymphoblastic, Acute, Philadelphia-positive 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Blood 0 0 0 0
Other blood disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dasatinib

Experimental: 1 -


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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major and overall hematologic response rates
Timepoint [1] 0 0
throughout the study
Secondary outcome [1] 0 0
Durability of hematologic response and time to hematologic response (major and overall)
Timepoint [1] 0 0
throughout the study
Secondary outcome [2] 0 0
Assess cytogenetic and molecular responses
Timepoint [2] 0 0
throughout the study
Secondary outcome [3] 0 0
Measure minor hematologic response rate in the imatinib resistant group
Timepoint [3] 0 0
throughout the study
Secondary outcome [4] 0 0
Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene
Timepoint [4] 0 0
throughout the study
Secondary outcome [5] 0 0
Measure the heath-related QOL using FACT-G
Timepoint [5] 0 0
throughout the study
Secondary outcome [6] 0 0
To assess safety and tolerability of dasatinib
Timepoint [6] 0 0
throughout the study
Secondary outcome [7] 0 0
Population PK
Timepoint [7] 0 0
first month

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Local Institution - St. Leonards
Recruitment postcode(s) [1] 0 0
- St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
B-Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Edegem
Country [20] 0 0
Belgium
State/province [20] 0 0
Yvoir
Country [21] 0 0
Brazil
State/province [21] 0 0
Campinas
Country [22] 0 0
Brazil
State/province [22] 0 0
Sao Paulo
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Denmark
State/province [25] 0 0
Aarhus
Country [26] 0 0
Finland
State/province [26] 0 0
Helsinki
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Lyon Cedex 03
Country [29] 0 0
France
State/province [29] 0 0
Nantes
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pessac
Country [32] 0 0
France
State/province [32] 0 0
Poitiers Cedex
Country [33] 0 0
France
State/province [33] 0 0
Strasbourg Cedex
Country [34] 0 0
Germany
State/province [34] 0 0
Frankfurt/Main
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Germany
State/province [36] 0 0
Mainz
Country [37] 0 0
Germany
State/province [37] 0 0
Mannheim
Country [38] 0 0
Israel
State/province [38] 0 0
Ramat-Gan
Country [39] 0 0
Italy
State/province [39] 0 0
Bologna
Country [40] 0 0
Italy
State/province [40] 0 0
Orbassano
Country [41] 0 0
Italy
State/province [41] 0 0
Roma
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Kyunggi-Do
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
Netherlands
State/province [44] 0 0
Nijmegen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Rotterdam
Country [46] 0 0
Norway
State/province [46] 0 0
Trondheim
Country [47] 0 0
Peru
State/province [47] 0 0
Lima
Country [48] 0 0
Sweden
State/province [48] 0 0
Gothenburg
Country [49] 0 0
Sweden
State/province [49] 0 0
Lund
Country [50] 0 0
Sweden
State/province [50] 0 0
Stockholm
Country [51] 0 0
Sweden
State/province [51] 0 0
Umea
Country [52] 0 0
Sweden
State/province [52] 0 0
Uppsala
Country [53] 0 0
Switzerland
State/province [53] 0 0
Basel
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Central
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00101595
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications