Assess the Safety, Tolerability Oral PU-H71 in Subjects Taking Ruxolitinib
Hematopoietic Malignancies
Leukemia
Unknown Primary
18 Years and older, Male and Female
PU-H71-01-003 (primary)
NCI-2019-03010
Summary
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.
Objectives
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).
Eligibility
- Subject is willing and able to provide written informed consent before any study-specific procedures are performed.
- Subject is willing to comply with all study procedures and restrictions.
- Subject is =18 years of age.
- Subject has confirmed diagnosis of PMF, Post-PV MF, or Post-ET MF.
- Subject has been receiving ruxolitinib therapy meeting the following criteria:
- Receiving ruxolitinib >3 months prior to enrollment.
- Stable dose for 8 weeks before starting therapy with PU-H71.
- Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of: • Persistent or worsening disease-related symptoms, including but not limited to fatigue, pruritus, night sweats, early satiety, and other symptoms as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) score of >12 points. AND • Documented splenomegaly of at least 5 cm below the costal margin as measured on inspiration by physical examination.
- Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
- Acceptable pre-study organ function during screening defined as:
- Absolute neutrophil count (ANC) =1000/µL.
- Platelet count =50,000/µL.
- Alanine aminotransferase or aspartate aminotransferase =2×upper limit of normal.
- Direct serum bilirubin = 1.5×upper limit of normal.
- Creatinine clearance >50 mL/min/1.73 m2 based on the Cockcroft Gault equation.
- If female and of childbearing potential (premenopausal and not surgically sterile), the subject:
- Must have a negative serum or urine pregnancy test at screening. The serum pregnancy test must be obtained prior to the first administration of PU-H71 (=72 hours prior to dosing) in all premenopausal women and women <2 years after the onset of menopause.
- Must agree to use an acceptable method of effective contraception for the duration of the study and for 13 weeks after receiving the last dose of study treatment.
- If male, the subject agrees to:
- Use an acceptable method of effective contraception for the duration of the study and for 13 weeks after receiving study treatment.
- Agrees to abstain from sperm donation for the duration of the study and for 13 weeks after receiving the last dose of study treatment
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