Study of XL228 in Subjects With Chronic Myeloid Leukemia or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia

A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL228 Administered Intravenously to Subjects With Chronic Myeloid Leukemia (CML) or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia (Ph+ ALL)

The purpose of this study is to determine the safest dose of the BCR-ABL inhibitor XL228, how often it should be taken, and how well people with leukemia tolerate XL228.

Study Overview

• Status: Terminated
• Conditions: Chronic Myeloid Leukemia; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
• Intervention / Treatment: Drug: XL228

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1678
      • UCLA School of Medicine
    • San Francisco, California, United States, 94143-1270
      • University of California San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center, Lombardi Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject has a confirmed pathologic diagnosis as evidenced by the presence of the BCR-Abl translocation [t(9;22)] by fluorescence in situ hybridization (FISH), cytogenetics, or quantitative polymerase chain reaction (QPCR) of one of the following:

   1. CML

      • Chronic phase (CP)
      • Accelerated phase (AP)
      • Blast phase (BP) OR
   2. Ph+ ALL

2. The subject has one of the following:

   • Known T315I Abl mutation
   • Known resistance to or intolerance of imatinib and dasatinib
   • At least one prior anti-leukemia therapy, including, but not limited to, interferon, imatinib, or dasatinib
3. The subject is at least 18 years old.
4. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. The subject has adequate organ function.
6. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
7. Sexually active subjects must use an accepted method of contraception during the course of the study.
8. Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

1. The subject has received interferon, imatinib, or dasatinib within 7 days of the first dose of XL228.
2. The subject has received an investigational agent or radiotherapy within 28 days of the first dose of XL228.
3. The subject has received immunosuppressive therapy (eg, cyclosporine, steroids, tacrolimus for graft-versus-host disease [GVHD]) within 28 days prior to the first dose of XL228.
4. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 from toxicities related to peripheral stem cell or bone marrow transplant.
5. The subject has not recovered to CTCAE v3.0 Grade ≤1 from adverse events (AEs) due to investigational drugs or other medications.
6. The subject has known allergy or hypersensitivity to any component of the investigational drug product.
7. The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. The subject is pregnant or breastfeeding.
9. The subject is known to be positive for the human immunodeficiency virus (HIV).
10. The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; once-weekly dosing	Drug: XL228; 1-hour IV infusion
Experimental: 2; twice-weekly dosing	Drug: XL228; 1-hour IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety, tolerability, and maximum tolerated dose of once-weekly and/or twice-weekly 1-hour intravenous (IV) infusion of XL228	Assessed at periodic visits

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate plasma pharmacokinetics and estimate renal elimination of once-weekly and twice-weekly 1-hour IV infusion of XL228	Assessed at periodic visits
Exploratory Outcomes: Evaluate hematologic and cytogenetic response and pharmacodynamic correlates of XL228 activity	Assessed at periodic visits

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: April 18, 2007
• First Submitted That Met QC Criteria: April 18, 2007
• First Posted (Estimate): April 20, 2007

Study Record Updates

• Last Update Posted (Estimate): August 21, 2015
• Last Update Submitted That Met QC Criteria: August 19, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Lymphocytic Leukemia; Myeloid Leukemia; Ph+ ALL
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
• Other Study ID Numbers: XL228-001