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

Primary Purpose

Chronic Myeloid Leukemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Bosutinib

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Leukemia, tyrosine kinase inhibitor, philadelphia chromosome, Myeloid, Philadelphia Positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

City of Hope National Medical Center
HealthONE Presbyterian
Rocky Mountain Cancer Centers
Georgetown University Hospital
Emory Clinic
Emory University Hospital
Winship Cancer Institute
Oncology Specialists, S.C.
Indiana Blood and Marrow Transplantation
LSU Health Sciences Center
University Of Maryland Medical Center
University Of Maryland
Roswell Park Cancer Institute
Hudson Valley Hematology and Oncology Associates
Westchester Oncology Hematology Group, P.C.
Westchester Oncology Hematology, Group, P.C.
New York Presbyterian Hospital
New York Presbyterian Hospital
University of Rochester Cancer Center Pharmacy
University of Rochester Medical Center Strong Memorial Hospital - James P. Wilmot Cancer Center
University of Rochester Medical Center
University of Rochester-James P. Wilmot Cancer Center
University of Rochester
Westchester Medical Center
Penn State Milton S Hershey Medical Center
MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center
The University of Texas
Virginia Commonwealth University
Hospital Italiano de la Plata
Hospital Britanico
Academia Nacional de Medicina-Instituto de Investigaciones Hematologicas
Instituto Medico Especializado Alexander Fleming
Clinica del Sol
Centro Medico S.A.
Hospital Jose Ramon Vidal
Hospital universitario austral
Royal Adelaide Hospital
Institute of Medical and Veterinary Science
Department of Clinical Haematology and Bone Marrow Transplantation
Royal Brisbane and Women's Hospital
Haematology and Oncology Clinics of Australia
Klinikum Kreuzschwestern Wels
Hospital Brigadeiro da Secretaria de Estado da Saude de Sao Paulo
Centro de Estudos da Disciplina dr Hematologia da Faculdade de Medicine do ABC
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
Hospital de Clinicas - Universidade Federal do Parana
Cross Cancer Institute
BC Cancer Agency - Cancer Centre for the Southern Interior
CancerCare Manitoba
University Health Network Princess Margaret Hospital
Sir Mortimer B. Davis, Jewish General Hospital
Instituto Clinico Oncologico del Sur
The First Hospital affiliated to the Medical School of Zhejiang University
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
The Department of Hematology, The Chinese PLA General Hospital
The Hematology Hospital of Chinese Academy of Medical Sciences
The Department of Hematology, Ruijin Hospital Affiliated to School of Medicine of Shanghai Jiaotong
Hospital Pablo Tobon Uribe
Fundacion Santa Fe de Bogota
Biomedicum Helsinki
Universitaet Mainz
University Hospital Carl Gustav Carus
Universitaetsklinikum Hamburg - Eppendorf
Universitaetsklinikum Hamburg-Eppendorf
Universitaetsklinikum Magdeburg A. oe. R.
III Medizinische Klinik und Poliklinik
Klinikum der Johann Gutenberg Universitaet Mainz
Universitaet Mainz Iii. Medizinische Klinik Abteilung Fuer Haematologie
Universitaetsklinikum Mainz
III. Medizinische Klinik
Pamela Youde Nethersole Eastern Hosp.
Queen Mary Hospital
Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo
Christian Medical College
University of Bologna
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
AOU-S.Orsola-Malpighi - Universita degli Studi di Bologna
Azienda Ospedaliera San Gerardo
The Catholic University of Korea, Seoul St. Mary Hospital
Dept. of Hematology
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Centro Oncologico Estatal ISSEMYM
VU University Medical Center
University Medical Center Groningen
UMCG - Pharmacy
Universitair Medisch Centrum Groningen
VUMC
Avd. for blodsykdommer
Hospital Nacional Edgardo Rebagliati Martins
State Healthcare Institution, Sverdlovsk Regional Clinical Hospital
Kirov Research Institute of Hematology and Blood transfusion of Roszdrav Hematology clinic
Hematological Research Centre of RAMS
Moscow regional Clinical Research Institute named after M.F Vladimirsky
Rostov State Medical University of Roszdrav
Saint Petersburg State Medical University Hematology Department
Singapore General Hospital
University of the Free State
University of Cape Town
Johannesburg Hospital
Clinical Haematology Unit
Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
Hospital Universitari Clinic de Barcelona
Hospital Universitario La Princesa
Hospital Clinico Universitario de Valencia (CHUV)
Akademiska University Hospital
National Taiwan University Hospital - Section of Hematology-Oncology
Northern Centre for Cancer Care - The Newcastle Upon Tyne Hospitals - NHS Foundation Trust
School of Clinical and Laboratory Sciences
Hammersmith Hospital
Clinical Research Facility

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SKI-606

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicity (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).

Maximum Tolerated Dose (MTD)

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 to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1

Plasma Decay Half-Life (t1/2) - Part 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

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

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

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

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

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 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

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

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

Accumulation Ratio (R)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Percentage of Participants With Confirmed Complete Hematologic Response (CHR) - Part 2

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

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)

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)

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

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

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

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)

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)

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

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

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.

Full Information

NCT ID

NCT00261846

First Posted

December 2, 2005

Last Updated

June 28, 2017

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00261846

Brief Title

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

Official Title

A Phase 1/2 Study Of Bosutinib (Ski-606) In Philadelphia Chromosome Positive Leukemias

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

January 18, 2006 (Actual)

Primary Completion Date

September 25, 2009 (Actual)

Study Completion Date

August 6, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloid Leukemia

Keywords

Leukemia, tyrosine kinase inhibitor, philadelphia chromosome, Myeloid, Philadelphia Positive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

571 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SKI-606

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Bosutinib

Other Intervention Name(s)

SKI-606

Intervention Description

Part 1, starting dose 400 mg oral, daily dosing in the dose-escalation component. Part 2, 500 mg oral, continuous, daily dosing.

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicity (DLT)

Description

Time Frame

Part 1 Baseline up to Day 28

Title

Maximum Tolerated Dose (MTD)

Description

Time Frame

Part 1 Baseline up to Day 28

Title

Maximum Observed Plasma Concentration (Cmax) - Part 1

Time Frame