An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib

ID#: NCT04485260

Age: 18 - 99 years

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: January 28, 2021

End Date: October 01, 2024

Contact Information:
John Mei
Summary: This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.

Inclusion Criteria:

- Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO)

- Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to study entry

- Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT

- Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0

- ECOG performance status of 0 to 2

Exclusion Criteria:

- Patients who are positive for TP53 mutations

- Documented disease progression or clinical deterioration any time while on ruxolitinib treatment

- Patients who have had a documented spleen response to ruxolitinib.

- Prior splenectomy

- Prior MDM2 inhibitor therapy or p53-directed therapy