PU-H71-01-003: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated with Ruxolitinib

PU-H71-01-003: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated with Ruxolitinib

Gender
Minimum Age
Maximum Age
Adults
Physicians
Winton, Elliott
Phases
I
Drugs
PU-H71-01-003 (1594)
Disease Sites
Leukemia, other
Locations
Winship Cancer Institute of Emory University
NCT ID
NCT03935555
Protocol Number
PU-H71-01-003
Contact
If interested in learning more about this clinical trial, please contact winshipcto@emory.edu or (404) 778-1868.

Title

PU-H71-01-003: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated with Ruxolitinib

Summary

Primary Objectives:

-To determine the safety and tolerability, including dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of PU-H71 in combination with ruxolitinib (dose escalation).

  • To confirm the safety profile and RP2D of PU-H71 in a dose expansion cohort (dose expansion).

-To determine the pharmacokinetics (PK) of PU-H71 under the conditions of this study.

Secondary Objectives:

-To assess treatment response using the 2013 revised International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) and European Leukemia Net (ELN).

Exploratory Objectives:

To conduct a correlative assessment of molecular, cytogenic and other biomarkers of disease activity and/or drug effect.

Detail

Primary Objectives:

-To determine the safety and tolerability, including dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of PU-H71 in combination with ruxolitinib (dose escalation).

  • To confirm the safety profile and RP2D of PU-H71 in a dose expansion cohort (dose expansion).

-To determine the pharmacokinetics (PK) of PU-H71 under the conditions of this study.

Secondary Objectives:

-To assess treatment response using the 2013 revised International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) and European Leukemia Net (ELN).

Exploratory Objectives:

To conduct a correlative assessment of molecular, cytogenic and other biomarkers of disease activity and/or drug effect.

Eligibility

Exclusion Criteria:

Subject has known active liver disease, including viral hepatitis or cirrhosis. Subject has known or suspected human immunodeficiency virus (HIV) or other active infections requiring acute or chronic treatment with systemic antibiotics. Conditions requiring topical antibiotics are acceptable. Subject has a QT interval corrected using Fridericia's formula (QTcF) >480 ms (corrected) in the screening or baseline ECG based on median value of ECG's obtained. Subject has left ventricular ejection fraction (LVEF) ≤50%, or below institution's lower limit of normal (whichever is lower), by echocardiogram or multigated acquisition (MUGA) scan. Subject has a history (or family history) of long QT syndrome. Subject has coronary artery disease with an ischemic event within 6 months prior to screening. Subject has a permanent cardiac pacemaker. Subject has history of a second primary malignancy within the past 2 years, except for the following (if appropriately treated and considered cured): Stage I endometrial, surgically treated cervical or prostate carcinoma, and non-melanoma skin cancer. Subject has significant uncontrolled medical condition within 6 months prior to screening, as determined by the Investigator. Subject has planned use of antineoplastic agents (chemotherapy or cytotoxic drugs), immunotherapy, experimental therapy, or biologic therapy for treatment of MPN with the exception of ruxolitinib. Subject uses systemic corticosteroids (ie, prednisone >12.5 mg/day or dexamethasone >2 mg/day) within 2 weeks prior to Cycle 1 Day 1. Subject has planned or current use of strong CYP3A4/5, CYP2D6, or CYP2C19 inhibitors or inducers within 1 week or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1. Subject has planned or current use of medications that carry a risk for Torsades de Pointes within 1 week or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1. Subject has planned or current use of herbal preparations/medications at least 7 days prior to Cycle 1 Day 1. Subject has previously received PU-H71. Subject has concurrent participation in any interventional studies (except PU-H71-Positive Emission Tomography (PET) Scan Studies) within 14 days or 5 half-lives (whichever duration is longer) of Cycle 1 Day 1. Subject has uncontrolled diabetes mellitus, in the judgment of the Investigator. Subject has any other condition or laboratory abnormality or receives any other treatment(s) that may increase the risk associated with study participation or may interfere with the interpretation of study results in the judgment of the Investigator. Subject has an active ocular condition that in the opinion of the Investigator, may alter visual acuity during the course of the study (ie, ocular inflammatory disease, etc.) or a history or anticipation of major ocular surgery (including cataract extraction, intraocular surgery, etc.) during the study. Women who are pregnant or breastfeeding or plan to become pregnant.