Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

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

Protein Kinase Inhibitors

Enzyme Inhibitors

Momelotinib (MMB) tablet administered orally once daily

Gilead Study Director

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

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

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)

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.

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.

The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI 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.

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.

Median hepcidin at trough was assessed predose at each study visit.

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Sierra Oncology LLC - a GSK company

All adverse events summarized were treatment-emergent, defined as any adverse event with an onset date on or after the momelotinib start date and no later than 30 days after permanent discontinuation of momelotinib or any adverse event leading to premature discontinuation of momelotinib.

Subjects received oral MMB at a starting dose of 200 mg once daily for 24 weeks (± 7 days) on study.

Momelotinib (MMB)

Subjects who became transfusion independent by Week 24

Transfusion Independence Responders

Subjects who did not become transfusion independent by Week 24

Transfusion Independence Non-Responders

Total

Age, Continuous

Sex: Female, Male

Black

White

Not Permitted

Other

Race/Ethnicity, Customized

Spleen Volume

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.

Total Symptom Score

RBC Units Transfused within 8 weeks prior to Enrollment

Hepcidin

Serum iron

Hemoglobin

Total iron binding capacity

Reticulocytes

Reticulocytes/erythrocytes

Erythropoietin

Erythrocytes

Hematocrit

Ferritin

Soluble transferrin receptor

Transferrin saturation

Unsaturated iron binding capacity

Platelets

Leukocytes

Blasts

Liver Iron Content

%pSTAT Stimulated CD3+/4+ T cell

%pSTAT %tSTAT Stimulated CD3+/4+ T cell Ratio

C-Reactive Protein

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.

GSK Response Center

Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 6 subjects discontinued prior to Week 12 and could not be evaluated over the minimum period required for assessment of the endpoint (12 weeks).

Transfusion Independence Response by Week 24

Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 3 subjects discontinued prior to Week 8 and could not be evaluated over the minimum period required for assessment of the endpoint (8 weeks).

Transfusion Response Rate by Week 24

Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that spleen volume at Week 24 was not available for 15 subjects.

Splenic Response Rate at Week 24

There were 3 subjects with missing TSS at baseline who were excluded from the analysis. Note that of the 38 subjects evaluated, 17 were missing Week 24 TSS assessments.

Spots Global Cancer Trial Database for Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial