Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias - Full Text View

Sponsor:	Pfizer
Information provided by (Responsible Party):	Pfizer
ClinicalTrials.gov Identifier:	NCT00261846

Purpose

This is an open-label, continuous daily dosing, two-part safety and efficacy study of SKI-606 (bosutinib) in Philadelphia chromosome positive leukemias (Ph+). Part 1 is a dose-escalation study in chronic phase Chronic Myelogenous Leukemia (CML) subjects to establish the maximum tolerated dose (MTD) in this subject population. Part 2 has begun after the completion of Part 1 and after a dose has been established for the compound in chronic phase subjects. Part 2 is a study of the the efficacy of 500mg daily oral SKI-606 (bosutinib) in patients with all phases of Ph+ CML and Ph+ Acute Lymphocytic Leukemia (ALL). The protocol will test the hypotheses that oral daily dosing of bosutinib at 500 mg will attain (1) Major Cytogenetic Response (MCyR) in chronic phase CML patients and (2) Overall Hematological Response (OHR) in advanced leukemia patients. Each phase of the disease will be evaluated as a separate cohort.

Condition	Intervention	Phase
Leukemia, Myeloid, Philadelphia Positive	Drug: Bosutinib	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1/2 Study Of SKI-606 In Philadelphia Chromosome Positive Leukemias

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome tetrasomy 18p

MedlinePlus related topics: Chronic Myeloid Leukemia Leukemia

Drug Information available for: Bosutinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Define the maximum tolerated dose (MTD) in patients with chronic myelogenous leukemia (CML) in chronic phase resistant or refractory to imatinib [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Major cytogenetic response (MCyR) rate for chronic phase CML patients [ Time Frame: Every 3 months until Year 2, every 6 months thereafter, until treatment failure ] [ Designated as safety issue: No ]
Overall hematological response (OHR) rate in advanced leukemia patients [ Time Frame: Monthly to Month 3, every 3 months until Year 2, every 6 months thereafter, until treatment failure ] [ Designated as safety issue: No ]
Population Pharmacokinetics [ Time Frame: Day 1 pre-dose, Hours 2, 4, 6; Day 21 pre-dose, hours 2, 4, 6 and 20-23; Pre-dose Days 84, 168, 252 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assess the safety of SKI-606 (bosutinib) during prolonged oral exposure in a leukemic population [ Time Frame: Day 1 to Treatment Failure ] [ Designated as safety issue: Yes ]

Enrollment:	573
Study Start Date:	January 2006
Estimated Study Completion Date:	April 2013
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: SKI-606	Drug: Bosutinib Part 1, starting dose 400 mg oral, daily dosing in the dose-escalation component. Part 2, 500 mg oral, continuous, daily dosing. Other Name: SKI-606

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ph+ CML or Ph+ ALL who are primarily refractory to full-dose imatinib (600 mg), have disease progression/relapse while on full-dose imatinib, or are intolerant of any dose of imatinib.
At least 3 months post stem cell transplantation
Able to take daily oral capsules/tablets reliably

Exclusion Criteria:

Subjects with Philadelphia chromosome, and bcr-abl negative CML
Overt leptomeningeal leukemia
Subjects without evidence of leukemia in bone marrow (extramedullary disease only)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00261846

Show 82 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011 Oct 27;118(17):4567-76. Epub 2011 Aug 24.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00261846 History of Changes
Other Study ID Numbers:	3160A4-200, B1871006, 3160A4-200-WW
Study First Received:	December 2, 2005
Last Updated:	January 12, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Leukemia
tyrosine kinase inhibitor
philadelphia chromosome

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms

Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012