A Safety Study of XL019 in Adults With Myelofibrosis

Myelofibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00522574
• Other study ID #: XL019-001
• Status: Terminated
• Phase: Phase 1
• First received: August 27, 2007
• Last updated: April 4, 2011
• Start date: August 2007

Study information

• Verified date: April 2011
• 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Myelofibrosis
• Myeloproliferative Disorders
• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• XL019
gelatin capsules supplied in 5-mg, 25-mg, and 100-mg strengths

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mt. Sinai School of Medicine	New York	New York
United States	UCSF - Division of Hematology/Oncology	San Francisco	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Determine plasma pharmacokinetics, evaluate pharmacodynamic correlates, and estimate renal elimination of XL019		Assessed at periodic visits	No
Secondary	Evaluate preliminary efficacy of XL019 as a single agent when administered orally		Assessed at periodic visits	No