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

This study has been terminated.
(Sponsor decision)
Sponsor:
Information provided by:
Exelixis
ClinicalTrials.gov Identifier:
NCT00464113
First received: April 18, 2007
Last updated: April 4, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Chronic Myeloid Leukemia
Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
Drug: XL228
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Safety, tolerability, and maximum tolerated dose of once-weekly and/or twice-weekly 1-hour intravenous (IV) infusion of XL228 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate plasma pharmacokinetics and estimate renal elimination of once-weekly and twice-weekly 1-hour IV infusion of XL228 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
  • Exploratory Outcomes: Evaluate hematologic and cytogenetic response and pharmacodynamic correlates of XL228 activity [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: May 2007
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
once-weekly dosing
Drug: XL228
1-hour IV infusion
Experimental: 2
twice-weekly dosing
Drug: XL228
1-hour IV infusion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464113

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

No publications provided

Responsible Party: Paul Woodard, MD/Director, Clinical Research, Exelixis, Inc.
ClinicalTrials.gov Identifier: NCT00464113     History of Changes
Other Study ID Numbers: XL228-001
Study First Received: April 18, 2007
Last Updated: April 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
Myeloid Leukemia
Lymphocytic Leukemia
Ph+ ALL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Abnormal Karyotype
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014