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

Study Overview
=================
Brief 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.

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)

Conditions
-----------------
Chronic Myeloid Leukemia, Leukemia, Lymphoblastic, Acute, Philadelphia-Positive

Intervention / Treatment
-----------------
* Drug: XL228


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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: CML Chronic phase (CP) Accelerated phase (AP) Blast phase (BP) OR Ph+ ALL 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 The subject is at least 18 years old. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2. The subject has adequate organ function. The subject is capable of understanding and complying with the protocol and has signed the informed consent document. Sexually active subjects must use an accepted method of contraception during the course of the study. Female subjects of childbearing potential must have a negative pregnancy test at enrollment. Exclusion Criteria: The subject has received interferon, imatinib, or dasatinib within 7 days of the first dose of XL228. The subject has received an investigational agent or radiotherapy within 28 days of the first dose of XL228. 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. 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. The subject has not recovered to CTCAE v3.0 Grade ≤1 from adverse events (AEs) due to investigational drugs or other medications. The subject has known allergy or hypersensitivity to any component of the investigational drug product. 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. The subject is pregnant or breastfeeding. The subject is known to be positive for the human immunodeficiency virus (HIV). The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>once-weekly dosing | Drug: XL228<br>* 1-hour IV infusion<br>|
| Experimental: 2<br>twice-weekly dosing | Drug: XL228<br>* 1-hour IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myeloid Leukemia, Lymphocytic Leukemia, Ph+ ALL