Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Pelabresib, Ruxolitinib.
- Who it may be relevant to
- Registry conditions: Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF), Post-essential Thrombocythemia Myelofibrosis (Post-ET MF). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Japan
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1b Study of Pelabresib (DAK539) add-on to Stable Dose of Ruxolitinib in Japanese Adult Patients With Myelofibrosis
Overview
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).
Detailed description
This study consists of three periods: screening, treatment, and follow-up. After a screening period of up to 28 days, between three and nine eligible and evaluable participants will be enrolled to receive pelabresib in addition to a stable dose of ruxolitinib.
The follow-up phase includes a 30-day safety follow-up and a long-term follow-up. Pelabresib will be administered until one of the following occurs: disease progression, unacceptable toxicity, death, participant decision, or investigator decision.
After discontinuation of pelabresib, safety assessments will continue with a safety follow-up visit 30 days after the last dose of pelabresib. Participants will then be contacted for long-term follow-up approximately every 12 weeks after the end of treatment (EOT) for at least three years from the first dose of pelabresib and for at least two years following the last dose of pelabresib, whichever is longer. Long-term follow-up will continue until death, withdrawal from the study, loss to follow-up, or completion of the follow-up period, whichever occurs first.
Safety follow-up and long-term follow-up visits will include assessment for leukemic transformation, which will be conducted throughout the study and for up to two years after treatment. The study will continue until all participants complete long-term follow-up or until access to pelabresib is ensured through a post-trial access program or reimbursement of pelabresib in Japan becomes available.
Japanese safety confirmation will be determined according to the decision rule. The starting dose is 125 milligrams once daily (QD), and no dose escalation or de-escalation for safety confirmation is planned in this study. Initially, three participants will receive 125 milligrams QD of pelabresib as an add-on to ruxolitinib. The dose-limiting toxicity (DLT) evaluation period for Japanese safety confirmation is 21 days (one cycle).
Interventions
- Drug Pelabresib
125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle - Drug Ruxolitinib
5-25 mg twice daily (BID)
Primary outcome measures
- Incidence of dose-limiting toxicities (DLTs) [Time frame: Up to 21 days]
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Time frame: Through study completion, an average of approximately 4 years]
Secondary outcome measures (6)
- Plasma concentration time profiles of pelabresib [Time frame: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Area Under the plasma concentration-time Curve (AUC) of pelabresib [Time frame: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Maximum observed plasma Concentration (Cmax) of pelabresib [Time frame: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Time to Maximum observed plasma Concentration (Tmax) of pelabresib [Time frame: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Absolute change from baseline and percentage change from baseline in spleen volume over time (Week 24 and 48), as measured by MRI (or CT scan). [Time frame: Baseline, Week 24, Week 48]
- Absolute change from baseline and percentage change from baseline in Total Symptom Score (TSS) over time (until Week 48), as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 [Time frame: Baseline and up to Week 48]
Eligibility criteria
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.
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Japan · 7 centers
- Novartis Investigative Site — Kamogawa
- Novartis Investigative Site — Sapporo
- Novartis Investigative Site — Kamakura
- Novartis Investigative Site — Kurashiki
- Novartis Investigative Site — Bunkyo Ku
- Novartis Investigative Site — Chūō
- Novartis Investigative Site — Kumamoto
Identifiers
NCT: NCT07340138 · CDAK539A11101