Active, not recruiting
Phase 1
Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis
Condition(s) studied
Primary Myelofibrosis (PMF)Post-polycythemia Vera Myelofibrosis (Post-PV MF)Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)
Investigational drug(s) / intervention(s)
Pelabresib: 125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle
Ruxolitinib: 5-25 mg twice daily (BID)
Study summary
This Phase 1b, multicenter, open-label study aims to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of pelabresib as add-on to ruxolitinib in Japanese patients with myelofibrosis (MF).
Eligibility
Key Inclusion Criteria:
* Participants have diagnosis of primary myelofibrosis (PMF), post-polycythemia vera MF (Post-PV MF) or post-essential thrombocythemia MF (Post-ET MF) according to the International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias 2022.
* DIPSS risk category intermediate-1, intermediate-2 or high-risk at screening.
* Participants currently treated with ruxolitinib monotherapy AND who are likely to benefit from the addition of pelabresib to ruxolitinib in the opinion of the investigator.
* Receiving ruxolitinib at a stable dose (5 to 25 mg BID) for at least 8 weeks prior to the first dose of pelabresib.
* Palpable spleen (spleen length below left costal margin \[LCM\] must be recorded) or documented splenomegaly by MRI or CT (image report must be recorded) at screening.
* Platelet count ≥ 100 × 10\^9/L in the absence of growth factor support (including thrombopoietin mimetics/agonists) or platelet transfusions 4 weeks prior to the first dose of pelabresib.
* Blasts \< 5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening.
Key Exclusion Criteria:
* Prior splenectomy at any time or splenic irradiation in the previous 6 months
* Prior hematopoietic cell transplant or participants anticipated to receive a hematopoietic cell transplant within 24 weeks from the first dose of pelabresib.
* Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase or leukemic transformation.
* History of a malignancy (other than MF, PV or ET) except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start of pelabresib, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years
* Received any approved or investigational agent for the treatment of MF except ruxolitinib within 14 days of first dose of pelabresib or within 5 half-lives of the approved or investigational agent, whichever is longer.
Other protocol-defined inclusion/exclusion criteria may apply.
Primary outcome measure(s)
- Incidence of dose-limiting toxicities (DLTs) — Up to 21 days
A dose-limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory finding that is not attributable to the underlying disease, disease progression, intercurrent illness or injury, or concomitant medications, occurring within the first 21 days of pelabresib treatment and meeting the protocol-specified criteria. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. For Japanese safety confirmation of the 125 mg QD dose, DLTs will be included in the decision-making process.
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) — Through study completion, an average of approximately 4 years
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Trial sites (3)
| Facility | City | Region | Status |
| Novartis Investigative Site |
Kamogawa |
Chiba |
|
| Novartis Investigative Site |
Sapporo |
Hokkaido |
|
| Novartis Investigative Site |
Chūō |
Yamanashi |
|
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