To Assess the Safety and Tolerability of INCB000928 in Participants With Myelodysplastic Syndromes or Multiple Myeloma

Multiple Myeloma Clinical Trial

— LIMBER  

Official title:

A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04582539
• Other study ID #: INCB 00928-105
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 19, 2021
• Est. completion date: September 21, 2024

Study information

• Verified date: January 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: September 21, 2024
• Est. primary completion date: September 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Anemia
• Multiple Myeloma
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Preleukemia
• Syndrome

Intervention

Drug:
• INCB000928
INCB000928 will be administered once daily.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre Benite
France	Institut Gustave Roussy	Villejuif
Italy	L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi (Aouc)	Firenze
Italy	Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo	Pavia
Italy	Irccs Istituto Clinico Humanitas	Rozzano
United States	University of Cincinnati	Cincinnati	Ohio
United States	Barbara Ann Karmanos Cancer Hospital	Detroit	Michigan
United States	Md Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Tulane Comprehensive Cancer Center	New Orleans	Louisiana
United States	Stanford Cancer Center	Palo Alto	California
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment-related adverse events	To determine the safety and tolerability of INCB000928 administered as monotherapy in participants with MDS or MM.	Approximately up to 7 months
Secondary	Proportion of participants with anemia response (for TI patients at baseline)	Defined as an Hgb increase.	Approximately up to 7 months
Secondary	Duration of anemia response	Defined as the interval from the first onset of anemia response to the earliest date of loss of anemia response.	Approximately up to 7 months
Secondary	Proportion of participants with RBC-TI (for TD at baseline)	Defined as the absence of any RBC transfusion	Approximately up to 7 months
Secondary	Duration of RBC-TI period	Defined as duration of time for which participants are transfusion independent	Approximately up to 7 months
Secondary	Rate of RBC transfusion	Defined as the average number of RBC units	Through weeks 12 and 24
Secondary	Increase in mean Hgb	Defined as the increase from baseline in the mean Hgb	Approximately up to 7 months
Secondary	MDS Participants only : Overall Response Rate	Defined as the proportion of participants with CR or PR	Approximately up to 7 months
Secondary	MDS Participants only : Progression Free Survival	Defined as the interval from the first dose of study drug until the first documented progression or death	Approximately up to 7 months
Secondary	MDS Participants only : Leukemia Free Survival	Defined as the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause.	Approximately up to 7 months
Secondary	MM participants only : Overall Response Rate	Defined as the proportion of participants with stringent CR, CR, very good PR, and PR	Approximately up to 7 months
Secondary	MM Participants only : Progression Free Survival	Defined as the interval from the first dose of study drug until the first documented progression or death.	Approximately up to 7 months
Secondary	Cmax	Maximum plasma concentration of INCB000928	C1D1 and C1D15
Secondary	Tmax	Time to reach maximum (peak) plasma concentration of INCB000928	C1D1 and C1D15
Secondary	AUC0-t	Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.	C1D1 and C1D15
Secondary	Hepcidin levels	Effect of INCB000928 on hepcidin levels	Approximately upto 7 months
Secondary	Iron Homeostasis	Effect of INCB000928 on iron homeostasis.	Approximately upto 7 months
Secondary	Erythropoiesis	Effect of INCB000928 on erythropoiesis.	Approximately upto 7 months