This is a multicenter, Phase 1b study with dose escalation and expansion cohorts designed to assess the safety, tolerability, PK, and preliminary efficacy of PU-H71 in subjects with PMF, Post-PV MF, Post-ET MF, taking stable doses of ruxolitinib.
The study will employ a standard 3+3 dose escalation design to determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), with additional subjects treated in a dose expansion cohort. The time period for collecting dose limiting toxicities (DLTs) is 1 cycle (21 days).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Marin Cancer Care - Greenbrae (California Cancer Care A Medical Group, Inc. - Greenbrae)
Larkspur, California, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
MD Anderson
Houston, Texas, United States
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including Cmax
Time frame: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including Tmax
Time frame: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including AUC0-t
Time frame: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including AUC0-inf
Time frame: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including CL
Time frame: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including t1/2
Time frame: 24 weeks
Assess Safety and Tolerability of PU-H71
Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in physical examinations
Time frame: 24 weeks
Assess Safety and Tolerability of PU-H71
Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in electrocardiograms (ECGs)
Time frame: 24 weeks
Assess Safety and Tolerability of PU-H71
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Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in vital signs
Time frame: 24 weeks
Assess Safety and Tolerability of PU-H71
Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in clinical laboratory evaluations
Time frame: 24 weeks
Assess treatment response of PU H71
Treatment response in myelofibrosis (MF) is to be evaluated using the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Time frame: 24 weeks
Assess treatment response of PU H71
Treatment response in myelofibrosis (MF) is to be evaluated using the revised European LeukemiaNet (ELN) response criteria.
Time frame: 24 weeks