Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis

NCT ID: NCT07340138

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-29
• Study Completion Date: 2031-03-07

Brief 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).

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).

Conditions

Primary Myelofibrosis (PMF); Post-polycythemia Vera Myelofibrosis (Post-PV MF); Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pelabresib + Ruxolitinib

Eligible participants will receive pelabresib 125 mg once daily (QD) in combination with ruxolitinib at doses ranging from 5 to 25 mg twice daily (BID).

Group Type: EXPERIMENTAL

Pelabresib

Intervention Type: DRUG

125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle

Ruxolitinib

Intervention Type: DRUG

5-25 mg twice daily (BID)

Interventions

Pelabresib

125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle

Intervention Type: DRUG

Ruxolitinib

5-25 mg twice daily (BID)

Intervention Type: DRUG

Other Intervention Names

DAK539; INC424

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Central Contacts

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

+41613241111

Other Identifiers

CDAK539A11101

Identifier Type: -

Identifier Source: org_study_id