Essential Thrombocythemia
Conditions
Keywords
calreticulin (CALR), mutCALR
Brief summary
This study is being conducted to evaluate INCA033989 versus best available therapy in participants with essential thrombocythemia and a CALR mutation previously treated with cytoreductive therapy.
Interventions
DRUGINCA033989
Administered intravenous (IV) in accordance with the protocol-defined requirements.
Best Available Therapy (BAT) will be selected by the investigator.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of high-risk ET. * Presence of mutCALR. * Prior treatment with at least 1 cytoreductive therapy.
Exclusion criteria
* Presence of any hematologic malignancy other than ET. * Major bleeding or thrombosis within the last 3 months prior to study enrollment. * Any prior allogenic or autologous stem-cell transplantation. * Unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities (Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy. * Prior nonhematologic malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease for more than 2 years before screening. Adequately treated carcinoma in situ without current evidence of disease. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable clinicohematologic response (DCR) | Week 24 | Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction from baseline in calreticulin exon 9 frameshift mutation(s) (mutCLAR) variant allele frequency (VAF) | Week 24 | Reduction in mutCALR VAF as defined in the protocol. |
| Durable clinicohematologic response (DCR) | Week 48 | Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol. |
| Durable partial clinicohematologic response (DPR) | Week 24 | Improvement of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol. |
| Longest duration of complete hematologic response (CHR) | Up to Week 48 | Longest time from documented CHR until the loss of CHR as defined in the protocol. |
| Number of Participants with Treatment Emergent Adverse Events (TEAE) | Up to Week 48 and 60 days after last dose | Defined as any adverse event occurring after the first dose of study drug until up to 60 days after the last dose of study drug. |
| TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment | Up to Week 48 and 60 days after last dose | TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment. |
| Number of participants with a reduction in mutCALR VAF | Week 24 and Week 48 | Number of participants with a reduction in mutCALR VAF as defined in the protocol. |
| Molecular response | Week 24 and Week 48 | Overall reduction in mutCALR VAF as defined in the protocol. |
| Change from baseline in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom score (TSS) | Up to Week 48 | Defined as the proportion of participants who achieve a protocol defined reduction in TSS. |
| Change from baseline in Brief Fatigue Inventory (BFI) fatigue score | Up to Week 48 | The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue. |
| Patient Global Impression of Change (PGIC) score | Up to Week 48 | The PGIC is based on a 7-point scale and the participant will rate each question from the start of treatment as 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Netherlands, Norway, Poland, South Korea, Spain, Switzerland, 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