Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

NCT02515630 | Completed Phase 2 Results

• 1 other identifier: GS-US-352-1672
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 13

Brief Summary

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

Conditions

Primary Myelofibrosis (PMF); Post-polycythemia Vera (Post-PV) Myelofibrosis; Postessential Thrombocythemia (Post-ET) Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Transfusion Independence Response by Week 24

  The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.

  From baseline to Week 24

Secondary Outcomes (24)

• Transfusion Response Rate by Week 24

  From baseline to Week 24

• Splenic Response Rate at Week 24

  Measured at Week 24

• Response Rate in Total Symptom Score (TSS) at Week 24

  Measured at Week 24

• Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change

  At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24

• Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin

  At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24

Study Arms (1)

Momelotinib

EXPERIMENTAL

MMB for 24 weeks (± 7 days)

Drug: MMB

Interventions

MMB DRUG

Momelotinib (MMB) tablet administered orally once daily

Also known as: GS-0387, CYT387

Momelotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (13)

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Orange, California, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

The Bronx, New York, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Related Publications (1)

• Harrison CN, Mesa R, Talpaz M, Gupta V, Gerds AT, Perkins A, Goh YT, Fox ML, McLornan D, Palmer J, Foltz L, Vannucchi A, Koschmieder S, Passamonti F, Lee SE, Ellis C, Strouse B, Gonzalez Carreras FJ, Oh ST. Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated With Momelotinib. Clin Lymphoma Myeloma Leuk. 2025 Mar;25(3):199-211. doi: 10.1016/j.clml.2024.10.001. Epub 2024 Oct 16.

  PMID: 39516087 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Pharmacokinetics parameters were removed as an analysis endpoint in the SAP due to the sparse PK samples collection. Change in circulating cytokine and inflammatory markers were limited to CRP as an analysis endpoint in the SAP.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: August 5, 2015
• Study Start: January 29, 2016
• Primary Completion: July 18, 2017
• Study Completion: August 15, 2017
• Last Updated: June 18, 2023
• Results First Posted: January 20, 2021

Record last verified: 2023-06

Locations

CA (1); US (12)