Phase 2
Completed N=41
Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Primary Myelofibrosis (PMF) · Post-polycythemia Vera (Post-PV) Myelofibrosis · Postessential Thrombocythemia (Post-ET) Myelofibrosis
Source: ClinicalTrials.gov NCT02515630 ↗
Enrolled (actual)
41
Serious AEs
34.2%
Results posted
Jan 2021
Primary outcomePrimary: Transfusion Independence Response by Week 24 — 34.1 percentage of subjects
Summary
This study will evaluate the transfusion independence response rate in transfusion-dependent adults with myelofibrosis after treatment with momelotinib (MMB).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Transfusion Independence Response by Week 24 |
34.1 | — |
| SECONDARY Transfusion Response Rate by Week 24 |
39.0 | — |
| SECONDARY Splenic Response Rate at Week 24 |
12.2 | — |
| SECONDARY Response Rate in Total Symptom Score (TSS) at Week 24 |
15.8 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change |
-1.7; 0.1; 0.0; -4.8; -11.2; -8.6 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin |
22.0; 42.4; 36.6; 19.7; 43.7; 36.5 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Serum Iron |
4.5; 5.9; 5.9; 39.8; 5.7; 13.3 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Hemoglobin |
12.8; 9.2; 9.9; 8.3; 6.3; 6.9 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity |
4.5; 2.0; 2.8; 6.7; 1.5; 2.2 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Reticulocytes |
33.6; -9.6; 2.9; 11.8; 5.5; 7.5 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% |
30.0; -16.3; -8.0; 8.2; 1.5; 4.1 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Erythropoietin |
-30.8; -8.1; -24.5; -45.0; 8.5; -4.4 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Erythrocytes |
5.2; 3.4; 3.4; 6.7; 3.6; 3.8 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Hematocrit |
8.9; 4.0; 4.5; 7.4; 0.0; 3.4 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Ferritin |
11.6; 8.8; 8.8; 19.1; 8.3; 13.6 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor |
4.0; -4.9; -4.8; -1.4; 8.8; 0.7 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation |
2.4; 13.5; 10.3; 36.4; 9.7; 10.5 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity |
0.0; -5.1; 0.0; -4.0; 0.0; -1.0 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Platelets |
21.4; -24.4; -9.5; 0.0; -29.7; -26.3 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Leukocytes |
11.6; -24.9; -14.9; 6.8; -4.7; 0.7 | — |
| SECONDARY Change in Markers of Iron Metabolism and Anemia - Blasts |
0; 3.0; 3.0; 0; 1.0; 1.0 | — |
| SECONDARY Change in Liver Iron Content |
4.7; 53.3; 22.3 | — |
| SECONDARY Change in Pharmacodynamics Biomarker - pSTAT3 |
-15.8; -13.5; -14.3; -17.1; -10.6; -12.8 | — |
| SECONDARY Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio |
-13.2; -15.5; -13.4; -9.6; -9.7; -9.7 | — |
| SECONDARY Change in Inflammatory Markers - C-Reactive Protein (CRP) |
-68.7; -53.7; -55.6; -67.8; -43.4; -48.9 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02515630). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.