Clinical trial NCT01998828: Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia
Official title: A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Polycythemia Vera
Essential Thrombocythemia
Keywords: Polycythemia
Polycythemia Vera
Essential Thrombocythemia
Thrombocytosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2013-12-02
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of either PV or ET as defined by the 2008 World Health Organization (WHO) Diagnostic Criteria
* Requires treatment for PV or ET, in the opinion of the study investigator
* Intolerant of, resistant to, or refuses current or available treatment for PV or ET
* Direct bilirubin ≤ 2.0 x upper limit of the normal range (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
* Calculated creatinine clearance (CrCl) of ≥ 45 mL/min
* Life expectancy \> 24 weeks
* Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
* Females who are nursing must agree to discontinue nursing before the first dose of study drug
* Able to comprehend and willing to sign informed consent form

Exclusion Criteria:

* Prior splenectomy
* Uncontrolled intercurrent illness, per protocol
* Known positive status for human immunodeficiency virus (HIV)
* Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
* Myeloproliferative neoplasm-directed therapy, other than aspirin, hydroxyurea, anagrelide, and/or phlebotomy, within 21 days prior to the first dose of study drug
* Anagrelide within 7 days prior to the first dose of study drug
* Presence of peripheral neuropathy ≥ Grade 2
* Unwilling or unable to take oral medication
* Prior use of a JAK1 or JAK2 inhibitor
* Use of strong CYP3A4 inducers within 1 week prior to the first dose of study drug
* QTc interval \> 450 msec, unless attributed to bundle branch block

Primary outcomes:
measure: Overall response rate
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Confirmed overall response rate
timeFrame: Up to 24 weeks
measure: Proportion of participants with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks
timeFrame: Up to 24 weeks
measure: Proportion of participants with WBC < 10 x 10^9/L that lasts at least 4 weeks
timeFrame: Up to 24 weeks
measure: Proportion of participants with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks
timeFrame: Up to 24 weeks
measure: Proportion of participants with resolution of palpable splenomegaly that lasts at least 4 weeks
timeFrame: Up to 24 weeks
measure: Proportion of participants with ≥ 10 point decrease in modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) compared to baseline that lasts at least 12 weeks
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Whittier
country: United States
state: California
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Houston
country: United States
state: Texas
city: Frankston
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: La Tronche
country: France
city: Nantes Cedex 1
country: France
city: Paris
country: France
city: Dresden
country: Germany
city: Minden
country: Germany
Study officials:
affiliation: Gilead Sciences
name: Peter Lee, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Verstovsek S, Courby S, Griesshammer M, Mesa RA, Brachmann CB, Kawashima J, Maltzman JD, Shao L, Xin Y, Huang D, Bajel A. A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia. Leuk Res. 2017 Sep;60:11-17. doi: 10.1016/j.leukres.2017.05.002. Epub 2017 May 30.