INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders

Phase 1

Active, not recruiting

Conditions: Post-essential Thrombocythemia Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Anemia

Interventions: Drug: INCB000928
Drug: ruxolitinib

Registration Number: NCT04455841

Lead Sponsor: Incyte Corporation

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 84

Inclusion Criteria

Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:
1. Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on 3 separate occasions with at least 7 days between measurements (Note: RBC transfusion must be at least 2 weeks before the Hgb measurement during screening).
2. Transfusion-dependent: Participant has received at least 4 units of RBC transfusions during the 28 days immediately preceding Cycle 1 Day 1 OR has received an average of at least 4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode must have occurred in the 28 days before Cycle 1 Day 1.
ECOG performance status score of the following:
1. 0 or 1 for the dose-escalation stages.
2. 0, 1, or 2 for the dose-expansion stage.
Life expectancy is greater than 6 months
Agreement to avoid pregnancy or fathering children.
Ineligible to receive or have not responded to available therapies for anemia such as ESAs.
For TGA:
Participants previously treated with JAK inhibitors for at least 12 weeks.
Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.
For TGB:
Participants must have been on a therapeutic and stable regimen of ruxolitinib for at least 12 consecutive weeks immediately preceding the first dose of study treatment.
Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.
For TGC:
Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib treatment.
Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

Exclusion Criteria

Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
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.
Laboratory Values outside of protocol defined range at screening.

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Group A (TGA)	INCB000928	INCB000928 will be administered once daily (QD).
Treatment Group C (TGC)	INCB000928	INCB000928 will be administered in combination with ruxolitinib.
Treatment Group B (TGB)	INCB000928	INCB000928 will be administered in combination with ruxolitinib.
Treatment Group B (TGB)	ruxolitinib	INCB000928 will be administered in combination with ruxolitinib.
Treatment Group C (TGC)	ruxolitinib	INCB000928 will be administered in combination with ruxolitinib.

Primary Outcome Measures

Name	Time	Method
Number of treatment-related adverse events	Approximately up to 13 months	To determine the safety and tolerability of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC).

Secondary Outcome Measures

Name	Time	Method
Mean Change of Hemoglobin	Approximately up to 13 months	Mean change in hemoglobin levels from baseline.
TGB and TGC only - Objective Response Rate	Approximately up to 13 months	Defined as the proportion of participants with Complete Response or Partial Response.
TGB and TGC only - Leukemia Free Survival	Approximately upto 13 months	Defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause.
Tmax	Approximately up to 13 months	Time to reach maximum (peak) plasma concentration of INCB 00928-104.
Iron Homeostasis	Approximately up to 13 months	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.
AUC0-t	Approximately up to 13 months	Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Anemia Response	Approximately up to 13 months	Defined as an increase in hemoglobin.
TGB and TGC only -Splenic Volume	Approximately up to 13 months	Defined as the proportion of participants achieving a targeted reduction in spleen volume.
TGB and TGC Only - Splenic Length	Approximately Up to 13 months	Defined as the proportion of participants achieving a targeted reduction in spleen length.
Hepcidin levels	Approximately up to 13 months	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on hepcidin levels.
Erythropoesis	Approximately up to 13 months	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.
Duration of Anemia Response	Approximately up to 13 months	Duration of anemia response at baseline.
Rate of RBC transfusion	Approximately up to 13 months	Defined as the average number of RBC units.
AUC	Approximately up to 13 months	Area Under the Plasma Concentration versus Time curve of INCB 00928-104.
TGB and TGC only - Progression Free Survival	Approximately up to 13 months	Defined as the interval from the first dose of study treatment until the first documented progression or death.

Trial Locations

Locations (34): Start Midwest
🇺🇸
Grand Rapids, Michigan, United States
Emory University-Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
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
Emory University - Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Weill Cornell Medical Centers
🇺🇸
New York, New York, United States
Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
🇺🇸
Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Md Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Princess Margaret Cancer Center
🇨🇦
Toronto, Ontario, Canada
McGill University Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier D'Angers
🇫🇷
Angers Cedex 01, France
Institut Paoli Calmettes
🇫🇷
Marseille Cedex 9, France
Hospital Saint Louis
🇫🇷
Paris, France
Azienda Ospedaliera Papa Giovanni Xxiii
🇮🇹
Bergamo, Italy
S Orsolas University Hospital Seragnoli Institute of Hematology
🇮🇹
Bologna, Italy
Azienda Ospedaliero-Universitaria Careggi (Aouc)
🇮🇹
Firenze, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
🇮🇹
Orbassano, Italy
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
🇮🇹
Pavia, Italy
Ospedale Santa Maria Della Misericordia Perugia
🇮🇹
Perugia, Italy
Tokyo Medical and Dental University Hospital
🇯🇵
Bunkyo-ku, Japan
Chiba Cancer Center
🇯🇵
Chiba, Japan
Gifu Municipal Hospital
🇯🇵
Gifu, Japan
Kansai Medical University Hospital
🇯🇵
Hirakata, Japan
Kumamoto Shinto General Hospital
🇯🇵
Kumamoto, Japan
Osaka International Cancer Institute
🇯🇵
Osaka, Japan
University Hospital of Wales
🇬🇧
Cardiff, WLS, United Kingdom
United Lincolnshire Hospitals
🇬🇧
Boston, United Kingdom
Lincoln County Hospital
🇬🇧
Lincoln, United Kingdom
Royal Cornwall Hospital Truro Sunrise Centre
🇬🇧
Truro, United Kingdom

INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders

Recruitment & Eligibility

Study & Design

Trial Locations

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