Clinical trial NCT04455841: INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders
Official title: A Phase 1/2 Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Anemia
Post-essential Thrombocythemia Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Keywords: anemia
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-07-02
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of treatment-related adverse events
timeFrame: Approximately up to 13 months
Secondary outcomes:
measure: Anemia Response
timeFrame: Approximately up to 13 months
measure: Duration of Anemia Response
timeFrame: Approximately up to 13 months
measure: Mean Change of Hemoglobin
timeFrame: Approximately up to 13 months
measure: Rate of RBC transfusion
timeFrame: Approximately up to 13 months
measure: TGB and TGC only -Splenic Volume
timeFrame: Approximately up to 13 months
measure: TGB and TGC Only - Splenic Length
timeFrame: Approximately Up to 13 months
measure: TGB and TGC only - Objective Response Rate
timeFrame: Approximately up to 13 months
measure: TGB and TGC only - Progression Free Survival
timeFrame: Approximately up to 13 months
measure: TGB and TGC only - Leukemia Free Survival
timeFrame: Approximately upto 13 months
measure: AUC
timeFrame: Approximately up to 13 months
measure: Tmax
timeFrame: Approximately up to 13 months
measure: AUC0-t
timeFrame: Approximately up to 13 months
measure: Hepcidin levels
timeFrame: Approximately up to 13 months
measure: Iron Homeostasis
timeFrame: Approximately up to 13 months
measure: Erythropoesis
timeFrame: Approximately up to 13 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Irvine
country: United States
facility: City of Hope Orange County
state: California
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: San Diego
country: United States
facility: Prebys Cancer Center
state: California
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University-Winship Cancer Institute
state: Georgia
city: Grand Rapids
country: United States
facility: Start Midwest
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical Centers
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: McGill University Jewish General Hospital
state: Quebec
city: Angers Cedex 01
country: France
facility: Centre Hospitalier D'Angers
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Hospital Saint Louis
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: S Orsolas University Hospital Seragnoli Institute of Hematology
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi (Aouc)
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
city: Pavia
country: Italy
facility: Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
city: Perugia
country: Italy
facility: Ospedale Santa Maria Della Misericordia Perugia
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Gifu
country: Japan
facility: Gifu Municipal Hospital
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto Shinto General Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: WLS
city: Boston
country: United Kingdom
facility: United Lincolnshire Hospitals
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital Truro Sunrise Centre
Study officials:
affiliation: Incyte Corporation
name: Amanda McBride, MD
role: STUDY_DIRECTOR
References: