A Safety Study of XL019 in Adults With Myelofibrosis

Sponsor

Exelixis (Industry)

Overall Status

Terminated

CT.gov ID

NCT00522574

Collaborator

(none)

100

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myeloproliferative Disorders Myelofibrosis Polycythemia Vera Thrombocythemia, Essential	Drug: XL019	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL019 Administered to Subjects With Myelofibrosis

Study Start Date :

Aug 1, 2007

Outcome Measures

Primary Outcome Measures

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. [Assessed at periodic visits]

Secondary Outcome Measures

Determine plasma pharmacokinetics, evaluate pharmacodynamic correlates, and estimate renal elimination of XL019 [Assessed at periodic visits]
Evaluate preliminary efficacy of XL019 as a single agent when administered orally [Assessed at periodic visits]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF - Division of Hematology/Oncology	San Francisco	California	United States	94143
2	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Mt. Sinai School of Medicine	New York	New York	United States	10029
5	MD Anderson Cancer Center	Houston	Texas	United States	77030