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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00261846




Registration number
NCT00261846
Ethics application status
Date submitted
2/12/2005
Date registered
5/12/2005
Date last updated
27/07/2017

Titles & IDs
Public title
Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias
Scientific title
A Phase 1/2 Study Of Bosutinib (Ski-606) In Philadelphia Chromosome Positive Leukemias
Secondary ID [1] 0 0
B1871006, 3160A4-200-WW
Secondary ID [2] 0 0
3160A4-200
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 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
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 - Bosutinib

Experimental: SKI-606 -


Treatment: Drugs: Bosutinib
Part 1, starting dose 400 mg oral, daily dosing in the dose-escalation component.

Part 2, 500 mg oral, continuous, daily dosing.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
Part 1 Baseline up to Day 28
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [2] 0 0
Part 1 Baseline up to Day 28
Primary outcome [3] 0 0
Maximum Observed Plasma Concentration (Cmax) - Part 1
Timepoint [3] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [4] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1
Timepoint [4] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [5] 0 0
Plasma Decay Half-Life (t1/2) - Part 1
Timepoint [5] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [6] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(0-48)] - Part 1
Timepoint [6] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [7] 0 0
Area Under the Concentration-Time Curve (AUC) - Part 1
Timepoint [7] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [8] 0 0
Apparent Oral Clearance (CL/F) - Part 1
Timepoint [8] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [9] 0 0
Apparent Volume of Distribution (Vz/F) - Part 1
Timepoint [9] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1
Primary outcome [10] 0 0
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) - Part 1
Timepoint [10] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15
Primary outcome [11] 0 0
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) - Part 1
Timepoint [11] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15
Primary outcome [12] 0 0
Plasma Decay Half-Life at Steady State (t1/2,ss) - Part 1
Timepoint [12] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15
Primary outcome [13] 0 0
Area Under the Concentration-Time Curve at Steady State (AUCss) - Part 1
Timepoint [13] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15
Primary outcome [14] 0 0
Apparent Oral Clearance at Steady State (CL/F,ss) - Part 1
Timepoint [14] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15
Primary outcome [15] 0 0
Accumulation Ratio (R)
Timepoint [15] 0 0
0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 1 and Day 15
Primary outcome [16] 0 0
Percentage of Participants With MCyR at Week 24 in Chronic Phase Second-line Imatinib Resistant CML Population - Part 2
Timepoint [16] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of Participants With Major Cytogenetic Response (MCyR) - Part 1
Timepoint [1] 0 0
Weeks 12, 24, 36, 48 and the end of active treatment phase of Part 1 (Week 52)
Secondary outcome [2] 0 0
Phosphorylation Inhibition of Breakpoint Cluster Region-Abelson Kinase (Bcr-Abl) - Part 1
Timepoint [2] 0 0
Baseline, Weeks 4, 8, 12, 24, 36, 48 and the end of the active treatment phase of Part 1 (Week 52)
Secondary outcome [3] 0 0
Phosphorylation Inhibition of Crk Like (CrkL) Protein at Baseline - Part 1
Timepoint [3] 0 0
0 (pre-dose) on Day 1 (Baseline)
Secondary outcome [4] 0 0
Percent Change From Baseline in Phosphorylation Inhibition of Crk Like Protein (CrkL) at Day 1, 8 and 15 - Part 1
Timepoint [4] 0 0
6 hours post-dose on Day 1, 0 (pre-dose), 6 hours post-dose on Day 8, 15
Secondary outcome [5] 0 0
Percentage of Participants With Major Cytogenetic Response (MCyR) in Chronic Phase Second-line and Chronic Phase Third-line CML Population - Part 2
Timepoint [5] 0 0
Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 4 (CP3L) or Year 5 (CP2L)
Secondary outcome [6] 0 0
Kaplan-Meier Estimate of Retaining an Attained/Maintained Major Cytogenetic Response (MCyR) at Year 5 in Chronic Phase Second-line CML - Part 2
Timepoint [6] 0 0
From first MCyR to loss of MCyR or censoring, assessed every 12 weeks up to 2 years and then every 24 weeks thereafter up to Year 5
Secondary outcome [7] 0 0
Time to Achieve Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML for Responders Only - Part 2
Timepoint [7] 0 0
Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 5
Secondary outcome [8] 0 0
Kaplan-Meier Estimate of Maintaining Complete Hematologic Response (CHR) at Year 4 (CP3L and ADV) or Year 5 (CP2L) - Part 2
Timepoint [8] 0 0
From date of first confirmed CHR to loss of CHR or censoring, assessed at Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 4 (CP3L and ADV) or Year 5 (CP2L)
Secondary outcome [9] 0 0
Duration of Complete Hematologic Response (CHR) - Part 2
Timepoint [9] 0 0
From date of first confirmed CHR to loss of CHR or censoring, assessed at Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 4 (CP3L and ADV) or Year 5 (CP2L)
Secondary outcome [10] 0 0
Time to Achieve Complete Hematologic Response (CHR) for Responders Only - Part 2
Timepoint [10] 0 0
Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 4 (CP3L and ADV) or Year 5 (CP2L)
Secondary outcome [11] 0 0
Cumulative Incidence of Progression/Death - Part 2
Timepoint [11] 0 0
Years 1, 2, 3, 4, and 5 (CP2L only)
Secondary outcome [12] 0 0
Progression Free Survival (PFS) - Part 2
Timepoint [12] 0 0
Years 1, 2, 3, 4, and 5 (CP2L only)
Secondary outcome [13] 0 0
Kaplan-Meier Estimate of Overall Survival (OS) - Part 2
Timepoint [13] 0 0
Years 1, 2, 3, 4, and 5 (CP2L only)
Secondary outcome [14] 0 0
Overall Survival (OS) - Part 2
Timepoint [14] 0 0
Years 1, 2, 3, 4, and 5 (CP2L only)
Secondary outcome [15] 0 0
Percentage of Participants With Confirmed Complete Hematologic Response (CHR) - Part 2
Timepoint [15] 0 0
Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 4 (CP3L and ADV) or Year 5 (CP2L)
Secondary outcome [16] 0 0
Percentage of Participants With Overall Hematologic Response (OHR) by Week 48 in Advanced Leukemia Population - Part 2
Timepoint [16] 0 0
Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 1 year
Secondary outcome [17] 0 0
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Timepoint [17] 0 0
Baseline up to follow up visit (30 days after last dose of study treatment)
Secondary outcome [18] 0 0
Duration of Potentially Clinically Important (PCI) Adverse Events (AEs)
Timepoint [18] 0 0
Baseline up to follow-up visit (30 days after last dose of study treatment)
Secondary outcome [19] 0 0
Percentage of Participants With Change From Baseline in Laboratory Tests Results
Timepoint [19] 0 0
Week 1, 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter
Secondary outcome [20] 0 0
Percentage of Participants With On-treatment PCI Change From Baseline in Electrocardiogram (ECG) Findings
Timepoint [20] 0 0
Baseline, 0 (pre-dose), 2, 4, 6 hours on Day 1, 0 (pre-dose), 2, 4, 6, 20-23 hours on Day 21, and end of treatment visit
Secondary outcome [21] 0 0
Number of Participants With Change From Baseline in Findings of Chest X-ray
Timepoint [21] 0 0
Baseline, Week 8, and end of treatment
Secondary outcome [22] 0 0
Number of Participants Who Received Concomitant Medications for Management of Adverse Events (AEs)
Timepoint [22] 0 0
Baseline and Weeks 1, 2, 3, 4, 8, 12, then every 12 weeks thereafter until end of treatment, for a mean duration of 28 months
Secondary outcome [23] 0 0
Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Timepoint [23] 0 0
Baseline, Week 1, 2, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter
Secondary outcome [24] 0 0
Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs
Timepoint [24] 0 0
Screening, Baseline, and end of treatment
Secondary outcome [25] 0 0
Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs and Number of Participants With PCI Values
Timepoint [25] 0 0
Post-therapy

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
18/01/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/08/2015
Sample size
Target
Accrual to date
Final
571
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Institute of Medical and Veterinary Science - Adelaide
Recruitment hospital [3] 0 0
Department of Clinical Haematology and Bone Marrow Transplantation - Melbourne
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Queensland
Recruitment hospital [5] 0 0
Haematology and Oncology Clinics of Australia - Queensland
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3181 - Melbourne
Recruitment postcode(s) [4] 0 0
4029 - Queensland
Recruitment postcode(s) [5] 0 0
4101 - Queensland
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
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
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
Argentina
State/province [13] 0 0
Provincia de Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Ciudad Autonoma de Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Corrientes
Country [17] 0 0
Argentina
State/province [17] 0 0
Pcia de Buenos Aires
Country [18] 0 0
Austria
State/province [18] 0 0
Wels
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo/sp - Brazil
Country [20] 0 0
Brazil
State/province [20] 0 0
Sp - Brazil
Country [21] 0 0
Brazil
State/province [21] 0 0
Sp Brazil
Country [22] 0 0
Brazil
State/province [22] 0 0
Curitiba, PR
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
Manitoba
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Chile
State/province [28] 0 0
Temuco
Country [29] 0 0
China
State/province [29] 0 0
P.r China
Country [30] 0 0
China
State/province [30] 0 0
P.r. China
Country [31] 0 0
China
State/province [31] 0 0
Shanghai
Country [32] 0 0
Colombia
State/province [32] 0 0
Antioquia
Country [33] 0 0
Colombia
State/province [33] 0 0
Cundinamarca
Country [34] 0 0
Finland
State/province [34] 0 0
Helsinki
Country [35] 0 0
Germany
State/province [35] 0 0
RP
Country [36] 0 0
Germany
State/province [36] 0 0
Dresden
Country [37] 0 0
Germany
State/province [37] 0 0
Hamburg
Country [38] 0 0
Germany
State/province [38] 0 0
Magdeburg
Country [39] 0 0
Germany
State/province [39] 0 0
Mainz
Country [40] 0 0
Germany
State/province [40] 0 0
Mannheim
Country [41] 0 0
Hong Kong
State/province [41] 0 0
Chai Wan
Country [42] 0 0
Hong Kong
State/province [42] 0 0
Hong Kong
Country [43] 0 0
Hungary
State/province [43] 0 0
Budapest
Country [44] 0 0
India
State/province [44] 0 0
Tamil Nadu
Country [45] 0 0
Italy
State/province [45] 0 0
Province of Bologna
Country [46] 0 0
Italy
State/province [46] 0 0
Torino
Country [47] 0 0
Italy
State/province [47] 0 0
Bologna
Country [48] 0 0
Italy
State/province [48] 0 0
Monza
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Seoul
Country [50] 0 0
Mexico
State/province [50] 0 0
Nuevo Leon
Country [51] 0 0
Mexico
State/province [51] 0 0
Toluca Estado de Mexico
Country [52] 0 0
Netherlands
State/province [52] 0 0
Amsterdam
Country [53] 0 0
Netherlands
State/province [53] 0 0
Groningen
Country [54] 0 0
Netherlands
State/province [54] 0 0
The Netherlands
Country [55] 0 0
Norway
State/province [55] 0 0
Norge
Country [56] 0 0
Peru
State/province [56] 0 0
Lima
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Ekaterinburg
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Kirov
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Moscow
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Rostov-on Don
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Saint Petersburg
Country [62] 0 0
Singapore
State/province [62] 0 0
Singapore
Country [63] 0 0
South Africa
State/province [63] 0 0
Bloemfontein
Country [64] 0 0
South Africa
State/province [64] 0 0
Cape Town
Country [65] 0 0
South Africa
State/province [65] 0 0
Parktown
Country [66] 0 0
South Africa
State/province [66] 0 0
Soweto
Country [67] 0 0
Spain
State/province [67] 0 0
Catalonia
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Valencia
Country [70] 0 0
Sweden
State/province [70] 0 0
Uppsala
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taipei 100
Country [72] 0 0
United Kingdom
State/province [72] 0 0
North East England
Country [73] 0 0
United Kingdom
State/province [73] 0 0
London
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Newcastle Upon Tyne, North East England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00261846