Myeloproliferative Neoplasms
Conditions
Keywords
Myeloproliferative Neoplasms, Myelofibrosis, Essential thrombocythemia, Polycythemia Vera
Brief summary
This study will be conducted to determine the safety, tolerability, dose-limiting toxicity (DLT)s, and maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)s of INCA036978 administered as monotherapy and in combination with a standard disease-directed therapy.
Interventions
DRUGINCA036978
INCA036978 will be administered at protocol defined dose.
A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Life expectancy \> 6 months. * Willingness to undergo a pretreatment and limited on-study BM biopsies and aspirates (as appropriate to disease). * Participants with MF, PV and ET as defined in the protocol.
Exclusion criteria
* Presence of any hematological malignancy other than MF, PV, or ET. * Malignancy within the last 3 years prior to enrollment. * Acute or chronic HBV, Active HCV or known HIV or tuberculosis infection. * Clinically significant or uncontrolled cardiac disease. * Has undergone any prior allogeneic stem-cell transplantation or such transplantation is planned in the next 6 months. * Laboratory values outside the Protocol-defined ranges. * Prior history of major bleeding or thrombosis within the last 3 months prior to study enrollment. * Presence of chronic or current active infectious disease requiring systemic treatment. * Treatment with an MPN-directed therapy (approved or investigational) within the per protocol threshold before the administration of study drug. * Prior radiation therapy within 28 days before the first dose of study treatment. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLT)s in Part 1 | Up to 28 days | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to approximately 2 years | Defined as adverse events AE (either reported for the first time or the worsening of a pre-existing event) occurring after the first dose of study drug and up to 60 days after last dose of study drug or until the start of a new disease-directed therapy, whichever occurs first. |
| Number of participants with TEAEs leading to dose modification or discontinuation | Up to approximately 2 years | Number of participants with TEAEs leading to study drug modifications (interruptions, dose reduction) or discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter: Cmax of INCA036978 | Up to approximately 2 years | Defined as maximum observed plasma concentration of INCA036978. |
| Pharmacokinetics Parameter: Tmax of INCA036978 | Up to approximately 2 years | Defined as the time to reach the maximum plasma concentration of INCA036978. |
| Pharmacokinetics Parameter: Cmax,ss of INCA036978 | Up to approximately 2 years | Defined as the maximum observed plasma concentration at steady state of INCA036978. |
| Pharmacokinetics Parameter: Cmin,ss of INCA036978 | Up to approximately 2 years | Defined as the minimum observed plasma concentration at steady state of INCA036978. |
| Pharmacokinetics Parameter: AUC(0-t) of INCA036978 | Up to approximately 2 years | Defined as the area under the concentration-time curve up to the last measurable concentration of INCA036978. |
| Pharmacokinetics Parameter: AUC 0-∞ of INCA036978 | Up to approximately 2 years | Defined as the area under the concentration-time curve from 0 to infinity of INCA036978. |
| Pharmacokinetics Parameter: CL/F of INCA036978 | Up to approximately 2 years | Defined as the apparent clearance of INCA036978. |
| Pharmacokinetics Parameter: Vz/F of INCA036978 | Up to approximately 2 years | Defined as the apparent volume of distribution of INCA036978. |
| Pharmacokinetics Parameter: t1/2 of INCA036978 | Up to approximately 2 years | Defined as the apparent terminal phase disposition half-life of INCA036978. |
| For participants with myelofibrosis (MF): Percentage of participants achieving spleen volume reduction as defined in the protocol | Week 12 and Week 24 | Defined as percentage of participants with a protocol defined spleen volume reduction. |
| For participants with MF and anemia: Anemia Response as defined in the protocol | Up to approximately 2 years | For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol. |
| For participants with polycythemia vera (PV): Peripheral blood count remission as defined by the protocol. | Up to approximately 2 years | Peripheral blood count remission as defined by the protocol. |
| For participants with essential thrombocythemia (ET): Peripheral blood count remission as defined by the protocol. | Up to approximately 2 years | Peripheral blood count remission as defined by the protocol. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed