Primary Myelofibrosis (PMF)Phase 1NCT03935555

Assess the Safety, Tolerability Oral PU-H71 in Subjects Taking Ruxolitinib

A Phase 1 study testing PU-H71 in people with Primary Myelofibrosis (PMF) and Post-Polycythemia Vera Myelofibrosis (Post-PV MF), run by Samus Therapeutics, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
What is being tested?: PU-H71
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 3 sitesUnited States
Study dates: 12 Aug 2019to 4 Nov 2022
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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

Who cannot join

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.

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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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

MD Anderson
Houston, Texas, 77030
Marin Cancer Care - Greenbrae (California Cancer Care A Medical Group, Inc. - Greenbrae)
Larkspur, California, 94904
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Phase 1b Study of PU-H71 for the Treatment of Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated With Ruxolitinib

Read the detailed description

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).

Conditions: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
Being tested: PU-H71
Keywords: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
Medical subject headings: Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PU-H71Drug
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome

Study groups in NCT03935555
Study group	Role	What they receive
Oral - 50mg	Experimental	PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). Receives: Drug: PU-H71
Oral -100 mg	Experimental	PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). Receives: Drug: PU-H71
Oral - 200 mg	Experimental	PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). Receives: Drug: PU-H71
Oral - 300 mg	Experimental	PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). Receives: Drug: PU-H71

What is being measured

The primary outcome is the main question the study is designed to answer.

Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including Cmax
Measured: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including Tmax
Measured: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including AUC0-t
Measured: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including AUC0-inf
Measured: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including CL
Measured: 24 weeks
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Determine the human exposure PK including t1/2
Measured: 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
Measured: 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)
Measured: 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 vital signs
Measured: 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
Measured: 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)
Measured: 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.
Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Aug 20194 Nov 2022

First posted2 May 2019
Study start12 Aug 2019
Primary completion19 Oct 2022
Study completion4 Nov 2022

Why it stopped: Samus Therapeutics company closure

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Primary Myelofibrosis (PMF)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: 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).
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03935555
Sponsor's protocol ID: PU-H71-01-003
Status last verified: Nov 2022
First submitted: 14 Mar 2019
Last updated: 17 Nov 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Flonoltinib Maleate Oral Regimens in Patients With Myelofibrosis
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A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms
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Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF)
Active, not recruitingPhase 2
Extended Access of Momelotinib in Adults With Myelofibrosis
Neoplasms, Post-polycythemia Vera Myelofibrosis (Post-PV MF)

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