Polycythemia Vera, Essential Thrombocythemia
Conditions
Keywords
Polycythemia, Polycythemia Vera, Essential Thrombocythemia, Thrombocytosis, Myeloproliferative Disorders, Bone Marrow Diseases, Hematologic Diseases, Blood Coagulation Disorders, Blood Platelet Disorders, Hemorrhagic Disorders
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.
Interventions
DRUGMomelotinib
Momelotinib tablet administered orally once daily
Sponsors
Sierra Oncology LLC - a GSK company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | Up to 24 weeks | For the PV Cohort, overall response rate (ORR) is defined as the proportion of participants with all of the following at some point during the treatment period: * Hematocrit \< 45% in the absence of phlebotomy that lasts at least 4 weeks * White blood cell (WBC) count \< 10 x 10\^9/L that lasts at least 4 weeks * Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks * Resolution of palpable splenomegaly that lasts at least 4 weeks For the ET Cohort, overall response rate is defined as the proportion of participants with all of the following at some point during the treatment period: * WBC count \< 10 x 10\^9/L that lasts at least 4 weeks * Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks * Resolution of palpable splenomegaly that lasts at least 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks | Up to 24 weeks | — |
| Proportion of participants with WBC < 10 x 10^9/L that lasts at least 4 weeks | Up to 24 weeks | — |
| Confirmed overall response rate | Up to 24 weeks | Confirmed overall response rate is defined as the proportion of participants who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks. |
| Proportion of participants with resolution of palpable splenomegaly that lasts at least 4 weeks | Up to 24 weeks | — |
| 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 | Up to 24 weeks | — |
| Proportion of participants with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks | Up to 24 weeks | — |
Countries
Australia, Canada, France, Germany, United States
Outcome results
None listed