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

NCT00811070 | Completed Phase 2 Results DMC

• 2 other identifiers: 3160A4-2203B1871007
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Chronic Myelogenous Leukemia

Keywords

CML. Chronic myelocytic leukemia. Philadelphia Chromosome. Japanese. SKI-606. Bosutinib. Imatinib resistant. Imatinib intolerant

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-Limiting Toxicity (DLT) - Part 1

  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.

  Baseline up to Day 28 (Part 1 )

• Maximum Tolerated Dose (MTD) - Part 1

  MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT.

  Baseline up to Day 28 (Part 1 )

• Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Second-line Cohort - Part 2

  Cytogenetic response (CyR) is based on the prevalence of Philadelphia chromosome 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 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.

  Week 24

Secondary Outcomes (21)

• Maximum Observed Plasma Concentration (Cmax) - Part 1

  Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

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

  Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

• Plasma Decay Half-Life (t1/2) - Part 1

  Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1

• Area Under the Concentration-Time Curve (AUC) - Part 1

  Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

• Apparent Oral Clearance (CL/F) - Part 1

  Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

Study Arms (1)

1

EXPERIMENTAL

Drug: SKI-606 (Bosutinib)

Interventions

SKI-606 (Bosutinib) DRUG

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.

1

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (23)

Kumamoto University Hospital

Kumamoto, Kumamoto, 860-8556, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Toyohashi Municipal Hospital

Aichi, 441-8570, Japan

Location

Japanese Red Cross Nagoya First Hospital

Aichi, 453-8511, Japan

Location

Aichi Cancer Center

Aichi, 464-8681, Japan

Location

Akita University Hospital

Akita, 010-8543, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Harasanshin Hospital

Fukuoka, 812-0033, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, 650-0047, Japan

Location

Hospital of Hyogo College of Medicine

Hyōgo, 663-8501, Japan

Location

Kanazawa University Hospital

Ishikawa, 920-8641, Japan

Location

Tokai University Hospital

Kanagawa, 259-1193, Japan

Location

University Hospital,Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Kinki University School of Medicine

Osaka, 589-8511, Japan

Location

Saga University Hospital

Saga, 846-8501, Japan

Location

Hamamatsu Medical Univ. HP Faculty of Medicine

Shizuoka, 431-3192, Japan

Location

Tokyo Metropolitan Cancer&Infectious disease Ctr Komagome Hp

Tokyo, 113-8677, Japan

Location

Japanese Red Cross Medical Center

Tokyo, 150-8935, Japan

Location

Jikei University Hospital Daisan

Tokyo, 201-8601, Japan

Location

Related Publications (3)

• Takahashi N, Cortes JE, Sakaida E, Ishizawa K, Ono T, Doki N, Matsumura I, Garcia-Gutierrez V, Rosti G, Ono C, Ohkura M, Tanetsugu Y, Viqueira A, Brummendorf TH. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol. 2022 Jun;115(6):838-851. doi: 10.1007/s12185-022-03314-y. Epub 2022 Mar 2.

  PMID: 35235189 DERIVED

• Takahashi N, Nakaseko C, Kobayashi Y, Miyamura K, Ono C, Koide Y, Fujii Y, Ohnishi K. Long-term treatment with bosutinib in a phase 1/2 study in Japanese chronic myeloid leukemia patients resistant/intolerant to prior tyrosine kinase inhibitor treatment. Int J Hematol. 2017 Sep;106(3):398-410. doi: 10.1007/s12185-017-2239-8. Epub 2017 Apr 13.

  PMID: 28409328 DERIVED

• Nakaseko C, Takahashi N, Ishizawa K, Kobayashi Y, Ohashi K, Nakagawa Y, Yamamoto K, Miyamura K, Taniwaki M, Okada M, Kawaguchi T, Shibata A, Fujii Y, Ono C, Ohnishi K. A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia. Int J Hematol. 2015 Feb;101(2):154-64. doi: 10.1007/s12185-014-1722-8. Epub 2014 Dec 25.

  PMID: 25540064 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2008
• First Posted: December 18, 2008
• Study Start: December 1, 2007
• Primary Completion: March 1, 2013
• Study Completion: June 1, 2015
• Last Updated: June 28, 2016
• Results First Posted: June 4, 2014

Record last verified: 2016-05

Locations

JP (23)