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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00811070
First received: December 17, 2008
Last updated: February 9, 2014
Last verified: February 2014
  Purpose

This is a two-part safety and efficacy study of SKI-606 in subjects who have Philadelphia chromosome positive leukemias (CML). Part 1 will be a dose-escalation study, in which an escalating dose of SKI-606 (Bosutinib), up to 600 mg, will be studied in subjects with imatinib resistant/refractory or imatinib intolerant chronic phase CML. Part 2 will evaluate the safety and efficacy of the maximum tolerated dose (MTD) of SKI-606 (Bosutinib)identified in Part 1 of the study.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: SKI-606 (Bosutinib)
Phase 1
Phase 2

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 (Bosutinib) Administered As A Single Agent In Japanese Subjects With Philadelphia Chromosome Positive Leukemias

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Part 1: Safety confirmation of establishment of Maximum tolerated dose. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Part 1: Evaluate the overall Pharmacokinetics parameters in this population. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Part 2: Determine the rate of attaining Major Cytogenetic Response. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 1: Determine the rate of Major Cytogenetic Response. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part 2: Estimate the time to and duration of Major Cytogenetic Response. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part 2: Estimate the time to and duration of Complete Hematologic Response. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part 2: Overall survival. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part 2: Progression free survival rates. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Part 2: Estimate the time to and duration of Overall Hematologic Response. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: December 2007
Estimated Study Completion Date: September 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: SKI-606 (Bosutinib)

Formulation: 100 mg Capsule for Part 1, 100 mg tablet for Part1 and Part 2.

SKI-606 (Bosutinib) will be taken by mouth with water and food as continuous once-daily dosing.


  Eligibility

Ages Eligible for Study:   20 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cytogenetic or Polymerase Chain Reaction based diagnosis of Chronic phase of Philadelphia Chromosome Positive Chronic Myelogenous Leukemia:

(Part 1), any phase of Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Part 2), whose disease is resistant/refractory to full-dose imatinib (400 mg for chronic phase subjects/600 mg for advanced leukemia subjects), or are intolerant of any dose of imatinib.

  • Adequate duration of prior imatinib therapy.
  • No prior exposure to Src, Abl, or Src/Abl kinase inhibitors other than imatinib.
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1 for chronic phase subjects, and 0, 1 or 2 for Advanced Stage subjects.
  • At least 7 days since any anti-proliferative treatment (including intrathecal chemotherapy) before the first dose of SKI-606, (except hydroxyurea).
  • Recovered to National Cancer Institute grade 0-1, or to baseline, from any toxicities of prior anti-tumor treatment, other than alopecia or thrombocytopenia due to active prior treatment (intolerant subjects).
  • At least 3 months post allogeneic stem cell transplantation before the first dose of SKI-606.
  • Able to take daily oral capsules reliably.
  • Absolute neutrophil count greater than 1,000/mL (Part 1)
  • Adequate hepatic, and renal function.
  • Documented normal INR if not on oral anticoagulant therapy, or, if on oral anticoagulant therapy consistent target INR less than 3.
  • Age should be greater than 20 years and less than 75 years (Part 1), greater than 20 years (Part 2), including women of childbearing potential.
  • Willingness of male and female subjects, who are not surgically sterile or postmenopausal, must agree and commit to the use of reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of SKI-606.

Exclusion Criteria:

  • Subjects with Philadelphia chromosome negative Chronic Myelogenous Leukemia.
  • Overt leptomeningeal leukemia. Subjects must be free of CNS involvement according to the symptoms for a minimum of 2 months before the first dose of SKI-606. Subjects with CNS symptoms must have a diagnostic lumbar puncture prior to study enrollment.
  • Subjects with extramedullary disease only.
  • Ongoing requirement for warfarin or other oral anticoagulant therapy (Part 1).
  • Ongoing requirement for hydroxyurea (Part 1).
  • Graft Versus Host Disease. a. no previous Graft Versus Host Disease allowed (Part 1). b. no treated or untreated Graft Versus Host Disease within 60 days of first dose (Part 2).
  • Major surgery within 14 days or radiotherapy within 7 days before the first dose of SKI-606 (recovery from any previous surgery should be complete before day 1).
  • Ongoing clinical requirement for administration of a strong inhibitor or inducer of CYP-3A4 (Part 1).
  • History of clinically significant or uncontrolled cardiac disease including: a. history of a clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) b. diagnosed or suspected congenital or acquired prolonged QT syndrome c. history of prolonged QTc d. unexplained syncope e. history of or active congestive heart failure f. myocardial infarction within 12 months. g. Uncontrolled angina or hypertension within 3 months.
  • Baseline QTcF greater than 0.45 sec (average of triplicate readings).
  • Concomitant use of or need for medications known to prolong the QT interval.
  • Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval.
  • Recent (within 14 days before the first dose of SKI-606) or ongoing clinically significant gastrointestinal disorder.
  • Pregnant or breastfeeding women.
  • Evidence of serious active infection, or significant medical or psychiatric illness.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00811070

Locations
Japan
Pfizer Investigational Site
Sendai-city, Miyagi, Japan
Pfizer Investigational Site
Chuo-ku, Tokyo, Japan
Pfizer Investigational Site
Aichi, Japan
Pfizer Investigational Site
Akita, Japan
Pfizer Investigational Site
Chiba, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Hyogo, Japan
Pfizer Investigational Site
Ishikawa, Japan
Pfizer Investigational Site
Kanagawa, Japan
Pfizer Investigational Site
Kumamoto, Japan
Pfizer Investigational Site
Kyoto, Japan
Pfizer Investigational Site
Okayama, Japan
Pfizer Investigational Site
Osaka, Japan
Pfizer Investigational Site
Saga, Japan
Pfizer Investigational Site
Shizuoka, Japan
Pfizer Investigational Site
Tokyo, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00811070     History of Changes
Other Study ID Numbers: 3160A4-2203, B1871007
Study First Received: December 17, 2008
Last Updated: February 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
CML. Chronic myelocytic leukemia. Philadelphia Chromosome. Japanese. SKI-606. Bosutinib. Imatinib resistant. Imatinib intolerant

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 April 15, 2014