To Assess the Safety and Tolerability of INCB000928 in Participants With Myelodysplastic Syndromes or Multiple Myeloma
- Conditions
- Myelodysplastic SyndromesAnemiaMultiple Myeloma
- Interventions
- Registration Number
- NCT04582539
- 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 in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- Agreement to avoid pregnancy or fathering children.
- Participants who are transfusion-dependent or present with symptomatic anemia
For MDS participants:
- Ineligible to receive or have not responded to available therapies for anemia such as ESAs or lenalidomide.
- Not requiring cytoreductive therapy other than hydroxyurea.
- BM and peripheral blood myeloblast count < 10%.
- Histologically confirmed diagnosis of the MDS, CMML and unclassifiable MDS/MPN overlap syndromes.
For MM participants:
- Histologically confirmed diagnosis of MM.
- After failure of available standard treatments such as alkylating agents, glucocorticoids, immunomodulatory drugs (lenalidomide,pomalidomide, or thalidomide), proteasome inhibitors (bortezomib or carfilzomib), and daratumumab.
- Any prior allogeneic stem cell transplantation or a candidate for such transplantation.
- Any major surgery within 28 days before the first dose of study drug.
- Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, or antibody or hypomethylating agent to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.
- Undergoing treatment with another investigational medication or having been treated with an investigational medication within 28 days before the first dose of study drug. -Undergoing treatment with ESAs, granulocyte colony-stimulating factor or granulocyte/macrophage colony-stimulating factor, romiplostin, or eltrombopag at any time within 28 days before the first dose of study drug.
- Undergoing treatment with a strong or potent inhibitor or inducer of CYP3A4/5 within 28 days or 5 half-lives (whichever is longer) before the first dose of study drug or expected to receive such treatment during the study.
- History of clinically significant or uncontrolled cardiac disease.
- History or presence of an abnormal ECG that, in the investigator's opinion, is clinically Meaningful.
- Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
- Diagnosis of chronic liver disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description INCB000928 INCB000928 INCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.
- Primary Outcome Measures
Name Time Method Number of treatment-related adverse events Approximately up to 7 months To determine the safety and tolerability of INCB000928 administered as monotherapy in participants with MDS or MM.
- Secondary Outcome Measures
Name Time Method Rate of RBC transfusion Through weeks 12 and 24 Defined as the average number of RBC units
MDS Participants only : Overall Response Rate Approximately up to 7 months Defined as the proportion of participants with CR or PR
MM Participants only : Progression Free Survival Approximately up to 7 months Defined as the interval from the first dose of study drug until the first documented progression or death.
AUC0-t C1D1 and C1D15 Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
MM participants only : Overall Response Rate Approximately up to 7 months Defined as the proportion of participants with stringent CR, CR, very good PR, and PR
Proportion of participants with anemia response (for TI patients at baseline) Approximately up to 7 months Defined as an Hgb increase.
Duration of RBC-TI period Approximately up to 7 months Defined as duration of time for which participants are transfusion independent
Cmax C1D1 and C1D15 Maximum plasma concentration of INCB000928
Duration of anemia response Approximately up to 7 months Defined as the interval from the first onset of anemia response to the earliest date of loss of anemia response.
Increase in mean Hgb Approximately up to 7 months Defined as the increase from baseline in the mean Hgb
MDS Participants only : Leukemia Free Survival Approximately up to 7 months Defined as the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause.
Iron Homeostasis Approximately upto 7 months Effect of INCB000928 on iron homeostasis.
Erythropoiesis Approximately upto 7 months Effect of INCB000928 on erythropoiesis.
Proportion of participants with RBC-TI (for TD at baseline) Approximately up to 7 months Defined as the absence of any RBC transfusion
MDS Participants only : Progression Free Survival Approximately up to 7 months Defined as the interval from the first dose of study drug until the first documented progression or death
Tmax C1D1 and C1D15 Time to reach maximum (peak) plasma concentration of INCB000928
Hepcidin levels Approximately upto 7 months Effect of INCB000928 on hepcidin levels
Trial Locations
- Locations (15)
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Barbara Ann Karmanos Cancer Hospital
🇺🇸Detroit, Michigan, United States
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
🇮🇹Pavia, Italy
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
🇫🇷Nantes, France
Hospices Civils de Lyon Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Azienda Ospedaliero-Universitaria Careggi (Aouc)
🇮🇹Firenze, Italy
Institut Gustave Roussy
🇫🇷Villejuif, France
University of Miami
🇺🇸Miami, Florida, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
🇮🇹Bologna, Italy
Tulane Comprehensive Cancer Center
🇺🇸New Orleans, Louisiana, United States