Clinical trial NCT02515630: Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Official title: A Phase 2, Open-label, Translational Biology Study of Momelotinib in Transfusion-Dependent Subjects With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Myelofibrosis (PMF)
Post-polycythemia Vera (Post-PV) Myelofibrosis
Postessential Thrombocythemia (Post-ET) Myelofibrosis
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2015-08-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the transfusion independence response rate in transfusion-dependent adults with myelofibrosis after treatment with momelotinib (MMB).


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of PMF or Post PV/ET-MF
* Requires myelofibrosis therapy, in the opinion of the investigator
* High risk OR intermediate-2 risk defined by dynamic international prognostic scoring system (DIPSS) OR intermediate-1 risk defined by DIPSS and associated with symptomatic splenomegaly and/or hepatomegaly
* Transfusion dependent at baseline, defined as ≥ 4 U red blood cell (RBC) transfusion in the 8 weeks prior to first dose of MMB
* Acceptable organ function as evidenced by the following:

  * Platelet Count ≥ 50 x 10\^9/L
  * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN) or AST or ALT ≤ 5 x ULN if liver is involved by disease process as judged by the investigator
  * Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance of ≥ 60 mL/min
  * Direct bilirubin ≤ 2.0 x ULN
* Life expectancy of \> 24 weeks
* Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
* Lactating females must agree to discontinue nursing before MMB administration
* Able to understand and willing to sign the informed consent form

Key Exclusion Criteria:

* Prior splenectomy
* Splenic irradiation within 3 months prior to the first dose of MMB
* Prior treatment with MMB
* Known positive status of human immunodeficiency virus (HIV)
* Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
* Use of strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks prior to the first dose of MMB
* Uncontrolled intercurrent illness per protocol
* Treatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMB
* Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
* Unwilling or unable to undergo a MRI per requirements in the study protocol
* Unwilling to consent to genomics sampling

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Transfusion Independence Response by Week 24
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Transfusion Response Rate by Week 24
timeFrame: From baseline to Week 24
measure: Splenic Response Rate at Week 24
timeFrame: Measured at Week 24
measure: Response Rate in Total Symptom Score (TSS) at Week 24
timeFrame: Measured at Week 24
measure: Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change
timeFrame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin
timeFrame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Serum Iron
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Hemoglobin
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Reticulocytes
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes%
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Erythropoietin
timeFrame: At Weeks 8 and 20
measure: Change in Markers of Iron Metabolism and Anemia - Erythrocytes
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Hematocrit
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Ferritin
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Platelets
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Leukocytes
timeFrame: At Weeks 2, 4, 8, 12, 16, 20 and 24
measure: Change in Markers of Iron Metabolism and Anemia - Blasts
timeFrame: At Weeks 2 and 4
measure: Change in Liver Iron Content
timeFrame: Measured at Week 24
measure: Change in Pharmacodynamics Biomarker - pSTAT3
timeFrame: On Day 1 and at Weeks 4 and 24
measure: Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio
timeFrame: On Day 1 and at Weeks 4 and 24
measure: Change in Inflammatory Markers - C-Reactive Protein (CRP)
timeFrame: At Weeks 2, 12 and 24
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Toronto
country: Canada
state: Ontario
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: