Myeloproliferative Neoplasms
Conditions
Keywords
Myeloproliferative Neoplasms, Ruxolitinib, Myelofibrosis, Essential thrombocythemia, CALR mutation
Brief summary
This study is being conducted to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a monotherapy or in combination with ruxolitinib in participants with myeloproliferative neoplasms.
Interventions
DRUGINCA033989
INCA033989 will be administered at protocol defined dose.
DRUGRuxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Sponsors
Incyte Corporation
Study design
Allocation
NON_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 regular on-study BM biopsies and aspirates (as appropriate to disease). * Existing documentation from a qualified local laboratory of CALR exon-9 mutation. * Participants with MF and ET as defined in the protocol.
Exclusion criteria
* Presence of any hematological malignancy other than ET, PMF, or post-ET MF. * Active invasive malignancy over the previous 2 years. * Active HBV/HCV, HIV. * History of clinically significant or uncontrolled cardiac disease. * Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned. * Laboratory values outside the Protocol-defined ranges. * Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment. * Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment. * Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. * For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | 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 3 years and 60 days | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib |
| Number of participants with TEAEs leading to dose modification or discontinuation | Up to 3 years and 60 days | Number of participants with TEAEs leading to dose modification or discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF | Up to 3 years and 60 days | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. |
| Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol | Up to 3 years and 60 days | Defined as percentage of participants with a protocol defined Spleen Volume Reduction. |
| Participants with MF with symptomatic anemia: Anemia Response | Up to 3 years and 60 days | 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. |
| Participants With ET: Response Rate | Up to 3 years and 60 days | Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug. |
| Participants With ET: Mean change from baseline of total symptom score (TSS) | Up to 3 years and 60 days | Mean change of TSS from baseline. |
| Mean change in disease-related allele burden | Up to 3 years and 60 days | Mean change in disease-related allele burden. |
| Pharmacokinetics Parameter: Cmax of INCA33989 | Up to 3 years and 60 days | Defined as maximum observed plasma concentration of INCA33989. |
| Pharmacokinetics Parameter: Tmax of INCA033989 | Up to 3 years and 60 days | Defined as the time to reach the maximum plasma concentration of INCA33989. |
| Pharmacokinetics Parameter: Cmin of INCA33989 | Up to 3 years and 60 days | Defined as the minimum observed plasma concentration of INCA33989. |
| Pharmacokinetics Parameter: AUC(0-t) of INCA33989 | Up to 3 years and 60 days | Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989. |
| Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 | Up to 3 years and 60 days | Defined as the area under the concentration-time curve from 0 to infinity of INCA33989. |
| Pharmacokinetics Parameter: CL/F of INCA33989 | Up to 3 years and 60 days | Defined as the apparent oral dose clearance of INCA33989. |
| Pharmacokinetics Parameter: Vz/F of INCA33989 | Up to 3 years and 60 days | Defined as the apparent oral dose volume of distribution of INCA33989. |
| Pharmacokinetics Parameter: t1/2 of INCA33989 | Up to 3 years and 60 days | Defined as the apparent terminal phase disposition half-life of INCA33989. |
Countries
Australia, Canada, Denmark, France, Germany, Italy, Japan, Spain, United Kingdom
Contacts
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed