Clinical trial NCT00522574: A Safety Study of XL019 in Adults With Myelofibrosis
Official title: A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL019 Administered to Subjects With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Myeloproliferative Disorders
Myelofibrosis
Polycythemia Vera
Thrombocythemia, Essential
Keywords: Myeloproliferative Disorders
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2007-08-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of XL019 in adults with myelofibrosis. XL019 is a selective inhibitor of the cytoplasmic tyrosine kinase JAK2. JAK2 is activated by cytokine and growth factor receptors and phosphorylates members of the STAT family of inducible transcription factors. Activation of the JAK/STAT pathway promotes cell growth and survival, and is a common feature of human tumors. JAK2 is activated by mutation in the majority of patients with myelofibrosis, polycythemia vera and essential thrombocytosis and appears to drive the inappropriate growth of blood cells in these conditions.


Eligibility criteria: Inclusion Criteria:

* The subject has primary myelofibrosis (PMF), post-polycythemia vera MF, or post-essential thrombocythemia MF and requires therapy, including subjects who have received prior MF-directed therapy and relapsed or subjects with refractory disease; or if newly diagnosed, then with intermediate or high risk according to the Lille scoring system.
* The subject is unwilling to undergo or is not a candidate for peripheral stem cell/bone marrow transplant.
* The subject is ≥18 years old.
* The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* The subject has adequate organ function.
* The subject has the capability of understanding the informed consent document and has signed the informed consent document.
* Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.
* Female subjects of childbearing potential must have a negative pregnancy test at screening.
* The subject has had no diagnosis of malignancy or evidence of other malignancy for 2 years prior to screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix).

Exclusion Criteria:

* The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within 3 months, or cardiac arrhythmias.
* The subject is pregnant or breastfeeding.
* The subject is known to be positive for the human immunodeficiency virus (HIV).
* The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Primary outcomes:
measure: To evaluate the safety, tolerability, maximum tolerated dose, and dose-limiting toxicities of XL019 as a single agent when orally administered in subjects with PMF, post-PV MF, or post-ET MF.
timeFrame: Assessed at periodic visits
Secondary outcomes:
measure: Determine plasma pharmacokinetics, evaluate pharmacodynamic correlates, and estimate renal elimination of XL019
timeFrame: Assessed at periodic visits
measure: Evaluate preliminary efficacy of XL019 as a single agent when administered orally
timeFrame: Assessed at periodic visits
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF - Division of Hematology/Oncology
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: