Anaemia associated with myelofibrosis whether as a de novo disorder (PMF) or evolve secondarily from previous PV or ET (post–PV MF or post–ET MF). MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10074689 Term: Post polycythemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspe
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Age 18 years or older at the time of signing the ICF. 3. ECOG performance status score of the following: a. 0 or 1 for the dose-escalation stages. b. 0, 1, or 2 for the dose-expansion stage. 4. Life expectancy is greater than 6 months. 5. Agreement to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease). 6. Agreement to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. b. Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR = 12 months of amenorrhea and at least 50 years of age) are eligible. 7. Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows: a. Anemia: An Hgb value =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation. 2. Any major surgery within 28 days before the first dose of study treatment. 3. Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib for TGB only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. 4. Undergoing treatment with another investigational medication or having been treated with an investigational medication within 28 days before the first dose of study treatment. 5. Undergoing treatment with a potent/strong inhibitor or inducer of CYP3A4/5 within 28 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study. 6. Any prior radiation therapy within 28 days before the first dose of study treatment. 7. Presence of any hematological malignancy other than PMF, post-PV, or post-ET MF, as applicable. 8. Active invasive malignancy over the previous 5 years. 9. Known active disease involving the CNS. 10. History of clinically significant or uncontrolled cardiac disease, including recent (within the last 12 months) unstable angina or acute myocardial infarction, or New York Heart Association Class III or IV congestive heart failure, or clinically significant arrhythmias not controlled by medication. 11. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. 12. Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. 13. Participants with diagnosis of chronic liver disease 14. Participants with known active hepatitis A, HBV, or HCV infection or who are HIV-positive. 15. Unwillingness to be transfused with blood components including RBC packs and platelet transfusions. 16. Any condition in the investigator's judgment that would interfere with full participation in the study. 17. Active alcohol or drug addiction that would interfere with their ability to comply with the study requirements. 18. Gastroesophageal reflux disease not controlled by medication within 28 days before the first dose of study treatment. 19. Has any unresolved toxicity = Grade 2 from previous therapy except for stable chronic toxicities (= Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy. 20. Known hypersensitivity, severe reaction, or any known contraindications to the use of any of the active substances or excipients in INCB000928 or ruxolitinib as appropriate to the relevant treatment group. 21. Women who are pregnant or breastfeeding. 22. Unable to swallow and retain oral medication. 23. Current use of prohibited medication 24. Participants with laboratory values at screening as defined. 25. Participants undergoing treatment with ESAs, G-CSF or GM-CSF, romiplostin, or eltrombopag at any time within 4 weeks before the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB).;Secondary Objective: To determine the efficacy of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB). To evaluate the PK of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib TGB). To evaluate the effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB) on hepcidin level, iron homeostasis, and erythropoiesis.;Primary end point(s): • Frequency and severity of AEs and SAEs, including changes in vital signs, ECGs, physical examinations, and clinical blood and urine laboratory parameters. • Identification of the DLTs, MTD, and RDE.;Timepoint(s) of evaluation of this end point: Safety and endpoint assessments will be performed throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Anemia response, defined as follows: - An Hgb increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period (84 days with each assessment meeting this requirement) during the first 24 weeks of treatment if TI at baseline OR - Achieving TI for any "rolling" 12-week period (absence of any RBC transfusion over any 84-day period) during the first 24 weeks of treatment if TD at baseline. • Duration of anemia response, defined as follows: - The interval from the first onset of anemia response to the earliest date of loss of anemia response that persists for at least 4 weeks or death from any cause (for the TI participants at baseline) OR - Duration of RBC-TI period for participants achieving RBC-TI for at least 12 consecutive weeks during the first 24 weeks of treatment (for the TD participants at baseline). • Mean change from baseline in the Hgb value over 12-week treatment periods. • Rate of RBC transfusion through Weeks 24 and 48, defined as the average number of RBC units per participant-month during the treatment period.;Timepoint(s) of evaluation of this end point: Endpoint assessments will be performed throughout the study. | — |
Countries
France, Italy, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed