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Drug Interventions

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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/24/2021.

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

Clinicaltrials.gov identifier NCT03935555

Recruitment Status Recruiting

First Posted May 2, 2019

Last update posted August 13, 2019

Study Description

Brief 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.

  • Condition or Disease:Post-Polycythemia Vera Myelofibrosis (Post-PV MF)
    Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
    Primary Myelofibrosis (PMF)
  • Intervention/Treatment: Drug: PU-H71
  • Phase: Phase 1
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).

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 24 participants
  • Allocation: Non-Randomized
  • Intervention Model: Sequential Assignment
  • Intervention 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) ()
  • Primary Purpose: Treatment
  • 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
  • Actual Study Start Date: August 2019
  • Estimated Primary Completion Date: May 2020
  • Estimated Study Completion Date: May 2020
Arms and interventions
Arm Intervention/treatment
Experimental: Oral - 200 mg
PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
Drug: PU-H71
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Experimental: Oral - 300 mg
PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
Drug: PU-H71
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Experimental: Oral - 50mg
PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
Drug: PU-H71
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Experimental: Oral -100 mg
PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
Drug: PU-H71
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Outcome Measures
  • Primary Outcome Measures: 1. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including Cmax
  • 2. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including Tmax
  • 3. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including AUC0-t
  • 4. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including AUC0-inf
  • 5. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including CL
  • 6. Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including t1/2
  • 7. Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in physical examinations
  • 8. Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in electrocardiograms (ECGs)
  • 9. Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in vital signs
  • 10. Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in clinical laboratory evaluations
  • 11. Assess treatment response of PU H71 [ Time Frame: 24 weeks ]
    Treatment response in myelofibrosis (MF) is to be evaluated using the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
  • 12. Assess treatment response of PU H71 [ Time Frame: 24 weeks ]
    Treatment response in myelofibrosis (MF) is to be evaluated using the revised European LeukemiaNet (ELN) response criteria.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Subject is willing and able to provide written informed consent before any
study-specific procedures are performed.

2. Subject is willing to comply with all study procedures and restrictions.

3. Subject is ≥18 years of age.

4. Subject has confirmed diagnosis of PMF, Post-PV MF, or Post-ET MF.

5. 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.

6. 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.

7. Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.

8. 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.

9. 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 480 ms
(corrected) in the screening or baseline ECG based on median value of ECG's obtained.

4. 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.

5. Subject has a history (or family history) of long QT syndrome.

6. Subject has coronary artery disease with an ischemic event within 6 months prior to
screening.

7. Subject has a permanent cardiac pacemaker.

8. 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.

9. Subject has significant uncontrolled medical condition within 6 months prior to
screening, as determined by the Investigator.

10. 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.

11. Subject uses systemic corticosteroids (ie, prednisone >12.5 mg/day or dexamethasone >2
mg/day) within 2 weeks prior to Cycle 1 Day 1.

12. 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.

13. 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.

14. Subject has planned or current use of herbal preparations/medications at least 7 days
prior to Cycle 1 Day 1.

15. Subject has previously received PU-H71.

16. 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.

17. Subject has uncontrolled diabetes mellitus, in the judgment of the Investigator.

18. 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.

19. 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.

20. Women who are pregnant or breastfeeding or plan to become pregnant.

Contacts and Locations
Contacts

Contact: Carol Becker 646-902-9376 beckerc@samustherapeutics.com

Locations

United States, California
Marin Cancer Care - Greenbrae (California Cancer Care A Medical Group, Inc. - Greenbrae)
Larkspur

United States, California
Ronald Reagan UCLA Medical Center
Los Angeles

United States, Texas
MD Anderson
Houston

Sponsors and Collaborators

Samus Therapeutics, Inc.

Investigators

Study Director: Hagop Youssoufian, M.D. Samus Therapeutics

More Information
  • Responsible Party: Samus Therapeutics, Inc.
  • ClinicalTrials.gov Identifier: NCT03935555 History of Changes
  • Other Study ID Numbers: PU-H71-01-003
  • First Posted: May 2, 2019 Key Record Dates
  • Last Update Posted: August 13, 2019
  • Last Verified: August 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Samus Therapeutics, Inc.: Primary Myelofibrosis (PMF)
    Post-Polycythemia Vera Myelofibrosis (Post-PV MF)
    Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
  • Additional relevant MeSH terms: Polycythemia Vera
    Primary Myelofibrosis
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential