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

June 14, 2023 updated by: Sierra Oncology LLC - a GSK company

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)

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
  • United States
    • Arizona
      • Phoenix, Arizona, United States
    • California
      • Los Angeles, California, United States
      • Orange, California, United States
    • Florida
      • Jacksonville, Florida, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Michigan
      • Ann Arbor, Michigan, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New York
      • Bronx, New York, United States
      • New York, New York, United States
    • North Carolina
      • Durham, North Carolina, United States
    • Ohio
      • Cleveland, Ohio, United States
    • Texas
      • Houston, Texas, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Momelotinib
MMB for 24 weeks (± 7 days)
Drug: MMB
Momelotinib (MMB) tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Transfusion Independence Response by Week 24
Time Frame: From baseline to 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Transfusion Response Rate by Week 24
Time Frame: From baseline to Week 24
The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study.
From baseline to Week 24
Splenic Response Rate at Week 24
Time Frame: Measured at Week 24
The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24.
Measured at Week 24
Response Rate in Total Symptom Score (TSS) at Week 24
Time Frame: Measured at Week 24
The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary. Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN. The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side). Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms. For this study, the TSS scale ranges from 0 to 70. The questionnaire was completed daily on an electronic diary device.
Measured at Week 24
Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change
Time Frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit. Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart. No momelotinib was administered on that day.
At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin
Time Frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
Median hepcidin at trough was assessed predose at each study visit.
At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Serum Iron
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Hemoglobin
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Reticulocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes%
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Erythropoietin
Time Frame: At Weeks 8 and 20
Percent change in erythropoietin at Weeks 8 and 20. The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 8 and 20
Change in Markers of Iron Metabolism and Anemia - Erythrocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Hematocrit
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Ferritin
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Platelets
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Leukocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 4, 8, 12, 16, 20 and 24
Change in Markers of Iron Metabolism and Anemia - Blasts
Time Frame: At Weeks 2 and 4
Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2 and 4
Change in Liver Iron Content
Time Frame: Measured at Week 24
Percent change from baseline in liver iron content assessed by MRI. The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Measured at Week 24
Change in Pharmacodynamics Biomarker - pSTAT3
Time Frame: On Day 1 and at Weeks 4 and 24
Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
On Day 1 and at Weeks 4 and 24
Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio
Time Frame: On Day 1 and at Weeks 4 and 24
Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
On Day 1 and at Weeks 4 and 24
Change in Inflammatory Markers - C-Reactive Protein (CRP)
Time Frame: At Weeks 2, 12 and 24
Percent change in C-reactive protein at Weeks 2, 12 and 24. The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
At Weeks 2, 12 and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sierra Oncology LLC - a GSK company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Gilead Study Director, Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 29, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 18, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 19, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-352-1672

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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