This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 administered as monotherapy or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia. This study will consist of 2 parts: dose escalation and expansion.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
INCB000928 will be administered at protocol defined dose.
Ruxolitinib will be administered at protocol defined dose.
City of Hope National Medical Center
Duarte, California, United States
City of Hope Orange County
Irvine, California, United States
Usc Norris Comprehensive Cancer Center
Los Angeles, California, United States
Stanford Cancer Center
Palo Alto, California, United States
Prebys Cancer Center
San Diego, California, United States
Number of treatment-related adverse events
To determine the safety and tolerability of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC).
Time frame: Approximately up to 13 months
Anemia Response
Defined as an increase in hemoglobin.
Time frame: Approximately up to 13 months
Duration of Anemia Response
Duration of anemia response at baseline.
Time frame: Approximately up to 13 months
Mean Change of Hemoglobin
Mean change in hemoglobin levels from baseline.
Time frame: Approximately up to 13 months
Rate of RBC transfusion
Defined as the average number of RBC units.
Time frame: Approximately up to 13 months
TGB and TGC only -Splenic Volume
Defined as the proportion of participants achieving a targeted reduction in spleen volume.
Time frame: Approximately up to 13 months
TGB and TGC Only - Splenic Length
Defined as the proportion of participants achieving a targeted reduction in spleen length.
Time frame: Approximately Up to 13 months
TGB and TGC only - Objective Response Rate
Defined as the proportion of participants with Complete Response or Partial Response.
Time frame: Approximately up to 13 months
TGB and TGC only - Progression Free Survival
Defined as the interval from the first dose of study treatment until the first documented progression or death.
Time frame: Approximately up to 13 months
TGB and TGC only - Leukemia Free Survival
Defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause.
Time frame: Approximately upto 13 months
AUC
Area Under the Plasma Concentration versus Time curve of INCB 00928-104.
Time frame: Approximately up to 13 months
Tmax
Time to reach maximum (peak) plasma concentration of INCB 00928-104.
Time frame: Approximately up to 13 months
AUC0-t
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Time frame: Approximately up to 13 months
Hepcidin levels
Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on hepcidin levels.
Time frame: Approximately up to 13 months
Iron Homeostasis
Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on iron homeostasis parameters such as TSI, ferritin, transferrin, TSAT, TIBC, UIBC, and serum NTBI.
Time frame: Approximately up to 13 months
Erythropoesis
Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on erythropoiesis parameters such as RC, NRBC, MCV, MCH, Hgb, Hct, RBC count, MCHC, and RDW.
Time frame: Approximately up to 13 months
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Emory University - Winship Cancer Institute
Atlanta, Georgia, United States
Emory University-Winship Cancer Institute
Atlanta, Georgia, United States
Start Midwest
Grand Rapids, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Weill Cornell Medical Centers
New York, New York, United States
...and 24 more locations