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

Chronic Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00464113
• Other study ID #: XL228-001
• Status: Terminated
• Phase: Phase 1
• First received: April 18, 2007
• Last updated: August 19, 2015
• Start date: May 2007
• Est. completion date: April 2011

Study information

• Verified date: August 2015
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: April 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• XL228
1-hour IV infusion

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	UCLA School of Medicine	Los Angeles	California
United States	University of California San Francisco	San Francisco	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Georgetown University Medical Center, Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, tolerability, and maximum tolerated dose of once-weekly and/or twice-weekly 1-hour intravenous (IV) infusion of XL228		Assessed at periodic visits	Yes
Secondary	Evaluate plasma pharmacokinetics and estimate renal elimination of once-weekly and twice-weekly 1-hour IV infusion of XL228		Assessed at periodic visits	No
Secondary	Exploratory Outcomes: Evaluate hematologic and cytogenetic response and pharmacodynamic correlates of XL228 activity		Assessed at periodic visits	No