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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00261846
First Posted: December 5, 2005
Last Update Posted: July 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  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
Chronic Myeloid Leukemia Drug: Bosutinib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study Of Bosutinib (Ski-606) In Philadelphia Chromosome Positive Leukemias

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Part 1 Baseline up to Day 28 ]
    DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).

  • Maximum Tolerated Dose (MTD) [ Time Frame: Part 1 Baseline up to Day 28 ]

    MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT. DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).

    NA = not estimable.


  • Maximum Observed Plasma Concentration (Cmax) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]
  • Plasma Decay Half-Life (t1/2) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

    NA = not estimable.


  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(0-48)] - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]
    AUC(0-48)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-48).

  • Area Under the Concentration-Time Curve (AUC) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]

    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

    NA = not estimable.


  • Apparent Oral Clearance (CL/F) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

    NA = not estimable.


  • Apparent Volume of Distribution (Vz/F) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  • Maximum Observed Plasma Concentration at Steady State (Cmax,ss) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15 ]
    Maximum plasma concentration over 24 hours at steady state (ss), on Day 15.

  • Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15 ]
    Time to reach maximum observed plasma concentration over 24 hours at steady state (ss), on Day 15.

  • Plasma Decay Half-Life at Steady State (t1/2,ss) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half-life over 24 hours at steady state (ss), on Day 15 was calculated.

  • Area Under the Concentration-Time Curve at Steady State (AUCss) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15 ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC over 24 hours at steady state (ss), on Day 15 was calculated.

  • Apparent Oral Clearance at Steady State (CL/F,ss) - Part 1 [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent oral clearence over 24 hours at steady state (ss), on Day 15 was calculated.

  • Accumulation Ratio (R) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 1 and Day 15 ]
    R=accumulation ratio (AUCss on Day 15/AUC0-24 on Day 1)

  • Percentage of Participants With MCyR at Week 24 in Chronic Phase Second-line Imatinib Resistant CML Population - Part 2 [ Time Frame: Week 24 ]
    CyR is based on the prevalence of Ph+ cells. Major cytogenetic response was categorized as either CCyR or partial CyR (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells from at least 20 metaphases from conventional bone marrow cytogenetics or less than (<) 1% positive cells from at least 200 cells analyzed from fluorescent in situ hybridization (FISH). PCyR was achieved when 1 to 35% Ph+ cells were present.


Secondary Outcome Measures:
  • Percentage of Participants With Major Cytogenetic Response (MCyR) - Part 1 [ Time Frame: Weeks 12, 24, 36, 48 and the end of active treatment phase of Part 1 (Week 52) ]
    Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0% Ph+ cells from at least 20 metaphases from conventional bone marrow cytogenetics or <1% positive cells from at least 200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present.

  • Phosphorylation Inhibition of Breakpoint Cluster Region-Abelson Kinase (Bcr-Abl) - Part 1 [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 48 and the end of the active treatment phase of Part 1 (Week 52) ]
    bcr-Abl is a protein resulting from the transcription of the Philadelphia chromosome following 9:22 chromosomal translocation, and phosphorylation inhibition of which correlates with inhibition of tumor cell growth.

  • Phosphorylation Inhibition of Crk Like (CrkL) Protein at Baseline - Part 1 [ Time Frame: 0 (pre-dose) on Day 1 (Baseline) ]
    CrkL is a protein, phosphorylation of which has been shown to correlate with CML cell growth; and conversely inhibition of their phosphorylation correlates with inhibition of tumor cell growth. Phosphorylation of CrkL was monitored in whole blood cells, as well as in the cluster of differentiation 3 (CD3+) (T cell), CD19+ (B cell) and CD34+ (blast cell) compartments by using fluorescent activated cell sorter (FACS) flow cytometry.

  • Percent Change From Baseline in Phosphorylation Inhibition of Crk Like Protein (CrkL) at Day 1, 8 and 15 - Part 1 [ Time Frame: 6 hours post-dose on Day 1, 0 (pre-dose), 6 hours post-dose on Day 8, 15 ]

    CrkL is a protein, phosphorylation of which has been shown to correlate with CML cell growth; and conversely inhibition of their phosphorylation correlates with inhibition of tumor cell growth. Phosphorylation of CrkL was monitored in whole blood cells, as well as in the CD3+ (T cell), CD19+ (B cell) and CD34+ (blast cell) compartments by using FACS flow cytometry.

    NA = not estimable.


  • Percentage of Participants With Major Cytogenetic Response (MCyR) in Chronic Phase Second-line and Chronic Phase Third-line CML Population - Part 2 [ Time Frame: 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) ]
    CyR is based on the prevalence of Ph+ cells. MCyR was categorized as either CCyR or PCyR. CCyR was achieved when there was 0% Ph+ cells from at least 20 metaphases from conventional bone marrow cytogenetics or <1% positive cells from at least 200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present.

  • Kaplan-Meier Estimate of Retaining an Attained/Maintained Major Cytogenetic Response (MCyR) at Year 5 in Chronic Phase Second-line CML - Part 2 [ Time Frame: 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 ]
    MCyR was categorized as either CCyR or PCyR. CCyR was achieved when there was 0% Ph+ cells from at least 20 metaphases from conventional bone marrow cytogenetics or <1% positive cells from at least 200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. The Kaplan-Meier probability of retaining an attained/maintained MCyR at Year 5 is reported. Median durations were not reached as of the minimum follow-up. Duration of response in weeks =(date of confirmed loss of first attained response or last valid cytogenetic assessment for those censored - date of first attained response)/7.

  • Time to Achieve Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML for Responders Only - Part 2 [ Time Frame: Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter up to Year 5 ]

    MCyR was categorized as either CCyR or PCyR. CCyR was achieved when there was 0% Ph+ cells from at least 20 metaphases from conventional bone marrow cytogenetics or <1% positive cells from at least 200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. Time to MCyR was the interval from the date of first dose of study medication until the first date of achieving a given response.

    Time to response in weeks equals (=) (event date minus (-) first dose date plus (+) 1)divided (/)7, where the event date is the non-missing date of the first attained response for responders only.


  • Kaplan-Meier Estimate of Maintaining Complete Hematologic Response (CHR) at Year 4 (CP3L and ADV) or Year 5 (CP2L) - Part 2 [ Time Frame: 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) ]

    Hematologic response: if participants met all of the following criteria of CHR: White Blood Cells equal to or less than (≤) institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count greater than or equal to (≥) 1.0×10^9 per liter (/L) , platelets ≥100×10^9/L & <450×10^9/L, <20% basophils in blood & no extramedually involvement (including hepato- or splenomegaly), ≤5% BM blasts (ADV only & applicable to CP if BM aspirate was performed). The duration of CHR was defined as the interval from the first date of response until the first date of confirmed loss of response. Duration of response in weeks =(date of confirmed loss of attained response or last valid hematologic assessment for those censored - date of first confirmed response)/7. The Kaplan-Meier estimate of maintaining CHR at the end of minimum follow-up is presented (CP2L: Year 5; CP3L & ADV: Year 4). NA = not estimable.

    NA = not estimable.


  • Duration of Complete Hematologic Response (CHR) - Part 2 [ Time Frame: 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) ]

    Hematologic response: if participants met all of the following criteria of CHR: White Blood Cells equal to or less than (≤) institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes less than (<)5% in blood, absolute neutrophil count greater than or equal to (≥) 1.0×10^9 per liter (/L) , platelets <450×10^9/L, platelets ≥100×10^9/L, <20% basophils in blood and no extramedually involvement (including hepato- or splenomegaly), ≤5% BM blasts (required for ADV only and applicable to CP if BM aspirate was performed). The duration of CHR was defined as the interval from the first date of response until the first date of confirmed loss of response. Duration of response in weeks =(date of confirmed loss of attained response or last valid hematologic assessment for those censored - date of first confirmed response)/7.

    NA = not estimable.


  • Time to Achieve Complete Hematologic Response (CHR) for Responders Only - Part 2 [ Time Frame: 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) ]
    The time to CHR was measured from the date of first dosing to the first date of response. Time to response in weeks = (event date - first dose date plus 1)/7, where the event date is the non-missing date of the first attained response for responders only.

  • Cumulative Incidence of Progression/Death - Part 2 [ Time Frame: Years 1, 2, 3, 4, and 5 (CP2L only) ]

    The cumulative incidence of on-treatment progression or death adjusting for the competing risk of treatment discontinuation without the event. Disease progression was determined by the investigator as the reason for treatment discontinuation and death was due to any cause within 30 days of last dose. Duration in months = (date of PD/death or last valid cytogenetic/hematologic assessment if censored - first dose date)/30.4. 95% confidence intervals were calculated using Gray's method.

    NA = not estimable. One year = 12 months.


  • Progression Free Survival (PFS) - Part 2 [ Time Frame: Years 1, 2, 3, 4, and 5 (CP2L only) ]

    PFS was based on Kaplan-Meier method. Disease progression was determined by the investigator as the reason for treatment discontinuation and death was due to any cause within 30 days of last dose. Duration in months = (date of PD/death or last valid cytogenetic/hematologic assessment if censored - first dose date)/30.4.

    NA = not estimable. One year = 12 months


  • Kaplan-Meier Estimate of Overall Survival (OS) - Part 2 [ Time Frame: Years 1, 2, 3, 4, and 5 (CP2L only) ]

    OS was based on Kaplan-Meier method. Survival was defined as the time period from the date of first dose of bosutinib to the date of death or date of last contact for those censored.

    NA = not estimable. One year = 12 months.


  • Overall Survival (OS) - Part 2 [ Time Frame: Years 1, 2, 3, 4, and 5 (CP2L only) ]

    OS was based on Kaplan-Meier method. Survival was defined as the time period from the date of first dose of bosutinib to the date of death or date of last contact for those censored.

    NA = not estimable. One year = 12 months.


  • Percentage of Participants With Confirmed Complete Hematologic Response (CHR) - Part 2 [ Time Frame: 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) ]
    Hematologic response: if participants met all of the following criteria of CHR: White Blood Cells ≤ institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count ≥ 1.0×10^9/L , platelets <450×10^9/L, platelets ≥100×10^9/L, <20% basophils in blood and no extramedually involvement (including hepato- or splenomegaly), ≤5% BM blasts (required for ADV only and applicable to CP if BM aspirate was performed).

  • Percentage of Participants With Overall Hematologic Response (OHR) by Week 48 in Advanced Leukemia Population - Part 2 [ Time Frame: 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 ]
    OHR included CHR, no evidence of leukemia (≤5% bone marrow blasts, no peripheral blood blasts or promyelocytes, <5% myelocytes + metamyelocytes in blood, white blood cells ≤ institutional upper limit of normal, 450x10^9/L > platelets > 20x10^9/L, absolute neutrophil count ≥0.5x10^9/L, <20% basophils in blood, no extramedullary involvement [including liver or spleen]), minor hematologic response (acute lymphoblastic leukemia [ALL] patients only, defined as <15% blasts in marrow & blood, <30% blasts + promyelocytes in marrow & blood, <20% basophils in peripheral blood & no extramedullary disease other than spleen & liver) or return to chronic phase (AP/BP participants, defined as <15% blasts in both peripheral blood &bone marrow, <30% blasts + promyelocytes in both peripheral blood & bone marrow, <20% basophils in both peripheral blood & bone marrow, no extramedullary Involvement other than liver or spleen). Participants had to meet at least 1 criterion.

  • Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to follow up visit (30 days after last dose of study treatment) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Duration of Potentially Clinically Important (PCI) Adverse Events (AEs) [ Time Frame: Baseline up to follow-up visit (30 days after last dose of study treatment) ]

    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. The event did not necessarily have a causal relationship with the treatment. PCI AEs included anemia, alanine aminotranferase (ALT), aspartate aminotransferase (AST), cardiac, diarrhea, edema, effusion, gastrointestinal, hemorrhage, hypersensitivity, hypertension, infection, liver, myelosuppression, nausea, neutropenia, rash, renal, thrombocytopenia, vomiting, and vascular events. Duration of AE was calculated as (stop date minus start date) plus 1 for non-missing and non-partial dates.

    NA = not estimable.


  • Percentage of Participants With Change From Baseline in Laboratory Tests Results [ Time Frame: Week 1, 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter ]
    Laboratory assessments included urinalysis, complete blood count (CBC), prothrombin time/partial prothromboplastin time (PT/PPT), international normalized ratio (INR), blood chemistry and serum pregnancy test (β-HCG). Parameters of special interest included liver function tests and those related to myelosuppression. Potentially clinically important (PCI) laboratory values were defined as National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher. Maximum CTCAE grade, and only participants who shifted to Grade 3/4 on-treatment, are reported.

  • Percentage of Participants With On-treatment PCI Change From Baseline in Electrocardiogram (ECG) Findings [ Time Frame: 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 ]
    Criteria for PCI changes in ECG (12-lead) were defined as: no sinus rhythm; PR interval >=220 msec and increase of >=20 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett formula (QTcB) >500 msec or increase of >60 msec; heart rate <=45 beats per minute (bpm) or >=120 bpm or decrease/increase of >=15 bpm.

  • Number of Participants With Change From Baseline in Findings of Chest X-ray [ Time Frame: Baseline, Week 8, and end of treatment ]
    Number of participants whose chest X-ray results changed (worsened or improved) from the Baseline.

  • Number of Participants Who Received Concomitant Medications for Management of Adverse Events (AEs) [ Time Frame: 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 ]
    Number of participants taking any non-study medications which were administered from Study Day 1 to 30 days after last dose of study treatment as a management of an AE are reported.

  • Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS) [ Time Frame: Baseline, Week 1, 2, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks thereafter ]
    ECOG-PS measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction;1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work;2=ambulatory (>50% of waking hrs), capable of all self care, unable to carry out any work activities;3=capable of only limited self care, confined to bed/chair >50% of waking hrs;4=completely disabled, cannot carry on any self care, totally confined to bed/chair;5=dead.

  • Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs [ Time Frame: Screening, Baseline, and end of treatment ]
    Percentage of participants with PCI physical examinations and vital signs is reported during therapy and at post therapy. Criteria for PCI change in vital signs: heart rate value of <40 beats per min and value >150 beats per min, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, respiratory rate (Resp) of <10 or >50 breaths/min and criteria for PCI change in physical examination: >=10% increase or decrease of body weight in kilogram (kg).

  • Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs and Number of Participants With PCI Values [ Time Frame: Post-therapy ]
    Percentage of participants with PCI physical examinations and vital signs is reported during therapy and at post therapy. Criteria for PCI change in vital signs: heart rate value of <40 beats per min and value >150 beats per min, SBP of <80 or >210 mmHg, DBP of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, Resp of <10 or >50 breaths/min and criteria for PCI change in physical examination: >=10% increase or decrease of body weight in kg. No Ph+ ALL participants were analyzed post-therapy (N=0). Part 1 safety data were originally presented in 2011 and are included as cumulative data in the Part 2 final safety results.


Enrollment: 571
Actual Study Start Date: January 18, 2006
Study Completion Date: August 6, 2015
Primary Completion Date: September 25, 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00261846


  Hide Study Locations
Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Colorado
HealthONE Presbyterian
Denver, Colorado, United States, 80218
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, District of Columbia
Georgetown University Hospital
Washington, D.C., District of Columbia, United States, 20007
United States, Georgia
Emory Clinic
Atlanta, Georgia, United States, 30322
Emory University Hospital
Atlanta, Georgia, United States, 30322
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
Oncology Specialists, S.C.
Niles, Illinois, United States, 60714
United States, Indiana
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, United States, 46237
United States, Louisiana
LSU Health Sciences Center
Shreveport, Louisiana, United States, 71103
United States, Maryland
University Of Maryland Medical Center
Baltimore, Maryland, United States, 21201
University Of Maryland
Baltimore, Maryland, United States, 21201
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Hudson Valley Hematology and Oncology Associates
Hawthorne, New York, United States, 10532
Westchester Oncology Hematology Group, P.C.
Hawthorne, New York, United States, 10532
Westchester Oncology Hematology, Group, P.C.
Hawthorne, New York, United States, 10532
New York Presbyterian Hospital
New York, New York, United States, 10021
New York Presbyterian Hospital
New York, New York, United States, 10065
University of Rochester Cancer Center Pharmacy
Rochester, New York, United States, 14642
University of Rochester Medical Center Strong Memorial Hospital - James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
University of Rochester Medical Center
Rochester, New York, United States, 14642
University of Rochester-James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
University of Rochester
Rochester, New York, United States, 14642
Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
The University of Texas
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0157
Argentina
Hospital Italiano de la Plata
La Plata, Provincia de Buenos Aires, Argentina, 1900
Hospital Britanico
Buenos Aires, Argentina, 1280
Academia Nacional de Medicina-Instituto de Investigaciones Hematologicas
Buenos Aires, Argentina, 1425
Instituto Medico Especializado Alexander Fleming
Buenos Aires, Argentina, 1426
Clinica del Sol
Ciudad Autonoma de Buenos Aires, Argentina, C1425DQI
Centro Medico S.A.
Corrientes, Argentina, 3400
Hospital Jose Ramon Vidal
Corrientes, Argentina, 3400
Hospital universitario austral
Pcia de Buenos Aires, Argentina, B1629ODT
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia
Institute of Medical and Veterinary Science
Adelaide, Australia, SA 5000
Department of Clinical Haematology and Bone Marrow Transplantation
Melbourne, Australia, 3181
Royal Brisbane and Women's Hospital
Queensland, Australia, 4029
Haematology and Oncology Clinics of Australia
Queensland, Australia, 4101
Austria
Klinikum Kreuzschwestern Wels
Wels, Austria, 4600
Brazil
Hospital Brigadeiro da Secretaria de Estado da Saude de Sao Paulo
Jardim Paulista, Sao Paulo/sp - Brazil, Brazil, CEP: 01401-901
Centro de Estudos da Disciplina dr Hematologia da Faculdade de Medicine do ABC
Santo Andre, Sp - Brazil, Brazil, CEP 09060-650
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
Sao Paulo, Sp Brazil, Brazil, 05403-000
Hospital de Clinicas - Universidade Federal do Parana
Curitiba, PR, Brazil, CEP: 80060-900
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G1Z2
Canada, British Columbia
BC Cancer Agency - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
University Health Network Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Sir Mortimer B. Davis, Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Chile
Instituto Clinico Oncologico del Sur
Temuco, Chile
China, P.r China
The First Hospital affiliated to the Medical School of Zhejiang University
Zhejiang, P.r China, China, 310003
China, P.r. China
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
Beijing, P.r. China, China, 100730
The Department of Hematology, The Chinese PLA General Hospital
Beijing, P.r. China, China, 100853
The Hematology Hospital of Chinese Academy of Medical Sciences
Tianjin, P.r. China, China, 300020
China
The Department of Hematology, Ruijin Hospital Affiliated to School of Medicine of Shanghai Jiaotong
Shanghai, China, 200025
Colombia
Hospital Pablo Tobon Uribe
Medellin, Antioquia, Colombia, 4459000
Fundacion Santa Fe de Bogota
Bogota, Cundinamarca, Colombia
Finland
Biomedicum Helsinki
Helsinki, Finland, FIN-00029 HUS
Germany
Universitaet Mainz
Mainz, RP, Germany, 55101
University Hospital Carl Gustav Carus
Dresden, Germany, 01307
Universitaetsklinikum Hamburg - Eppendorf
Hamburg, Germany, 20246
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitaetsklinikum Magdeburg A. oe. R.
Magdeburg, Germany, 39120
III Medizinische Klinik und Poliklinik
Mainz, Germany, 55101
Klinikum der Johann Gutenberg Universitaet Mainz
Mainz, Germany, 55131
Universitaet Mainz Iii. Medizinische Klinik Abteilung Fuer Haematologie
Mainz, Germany, D-55101
Universitaetsklinikum Mainz
Mainz, Germany
III. Medizinische Klinik
Mannheim, Germany, 68169
Hong Kong
Pamela Youde Nethersole Eastern Hosp.
Chai Wan, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Hungary
Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo
Budapest, Hungary, 1096
India
Christian Medical College
Vellore, Tamil Nadu, India, 632 004
Italy
University of Bologna
Bologna, Province of Bologna, Italy, 40138
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
Orbassano, Torino, Italy, 10043
AOU-S.Orsola-Malpighi - Universita degli Studi di Bologna
Bologna, Italy, 40138
Azienda Ospedaliera San Gerardo
Monza, Italy, 20900
Korea, Republic of
The Catholic University of Korea, Seoul St. Mary Hospital
Seoul, Korea, Republic of, 137-701
Dept. of Hematology
Seoul, Korea, Republic of, 138736
Mexico
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Nuevo Leon, Mexico, 64460
Centro Oncologico Estatal ISSEMYM
Toluca Estado de Mexico, Mexico, CP50180
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
UMCG - Pharmacy
Groningen, Netherlands, 9713 AP
Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9713 GZ
VUMC
The Netherlands, Netherlands
Norway
Avd. for blodsykdommer
Trondheim, Norge, Norway, 7006
Peru
Hospital Nacional Edgardo Rebagliati Martins
Lima, Peru, 11
Russian Federation
State Healthcare Institution, Sverdlovsk Regional Clinical Hospital
Ekaterinburg, Russian Federation, 620102
Kirov Research Institute of Hematology and Blood transfusion of Roszdrav Hematology clinic
Kirov, Russian Federation, 610027
Hematological Research Centre of RAMS
Moscow, Russian Federation, 125167
Moscow regional Clinical Research Institute named after M.F Vladimirsky
Moscow, Russian Federation, 129110
Rostov State Medical University of Roszdrav
Rostov-on Don, Russian Federation, 344022
Saint Petersburg State Medical University Hematology Department
Saint Petersburg, Russian Federation, 197022
Singapore
Singapore General Hospital
Singapore, Singapore, 169608
South Africa
University of the Free State
Bloemfontein, South Africa, 9301
University of Cape Town
Cape Town, South Africa, 7925
Johannesburg Hospital
Parktown, South Africa, 2193
Clinical Haematology Unit
Soweto, South Africa, 2013
Spain
Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
Barcelona, Catalonia, Spain, 08036
Hospital Universitari Clinic de Barcelona
Barcelona, Catalonia, Spain, 08036
Hospital Universitario La Princesa
Madrid, Spain, 28006
Hospital Clinico Universitario de Valencia (CHUV)
Valencia, Spain, 46010
Sweden
Akademiska University Hospital
Uppsala, Sweden, 75185
Taiwan
National Taiwan University Hospital - Section of Hematology-Oncology
Taipei 100, Taiwan, 10018
United Kingdom
Northern Centre for Cancer Care - The Newcastle Upon Tyne Hospitals - NHS Foundation Trust
Newcastle Upon Tyne, North East England, United Kingdom, NE7 7DN
School of Clinical and Laboratory Sciences
University upon Tyne, North East England, United Kingdom, NE1 7RU
Hammersmith Hospital
London, United Kingdom, W12 0HS
Clinical Research Facility
Newcastle Upon Tyne, North East England, United Kingdom, NE1 4LP
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

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

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00261846     History of Changes
Other Study ID Numbers: 3160A4-200
B1871006, 3160A4-200-WW
2005-004230-40 ( EudraCT Number )
B1871006 ( Other Identifier: Alias Study Number )
First Submitted: December 2, 2005
First Posted: December 5, 2005
Results First Submitted: October 4, 2012
Results First Posted: March 12, 2013
Last Update Posted: July 27, 2017
Last Verified: June 2017

Keywords provided by Pfizer:
Leukemia
tyrosine kinase inhibitor
philadelphia chromosome
Myeloid
Philadelphia Positive

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes