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.
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
- Are there results?
- None posted in the registry
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.
Show all 24Show fewer
- 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.
Show all 20Show fewer
- 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
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
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 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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Samus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Silverman, M.D., Study director, Samus Therapeutics
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
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03935555
- Acronym / sponsor ID
- PU-H71-01-003
- Conditions
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
- Keywords
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Samus Therapeutics company closure
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Samus Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Aug 2019 (actual)
- Primary completion
- 19 Oct 2022 (actual)
- Study completion
- 4 Nov 2022 (actual)
- First posted
- 2 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- 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).
| Arm | Type | Receives |
|---|---|---|
| Oral - 50mg | Experimental | Drug: PU-H71PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). |
| Oral -100 mg | Experimental | Drug: PU-H71PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). |
| Oral - 200 mg | Experimental | Drug: PU-H71PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). |
| Oral - 300 mg | Experimental | Drug: PU-H71PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PU-H71PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome | Drug | Oral - 200 mg, Oral - 300 mg, Oral - 50mg, Oral -100 mg |
Primary outcome
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including Cmax
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including Tmax
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including AUC0-t
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including AUC0-inf
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including CL
Assess Safety, Tolerability and Pharmacokinetics of PU-H71
Time frame: 24 weeks
Determine the human exposure PK including t1/2
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
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)
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
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
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)
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.
Results and safety
The study was stopped early (reason given: Samus Therapeutics company closure). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2022.
- Individual participant dataSharing planned: No
Related trials for Primary Myelofibrosis (PMF)
RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)
Not yet recruitingPhase 1
Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT
High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation
Not yet recruiting
Peri-Transplant Gecacitinib in Patients With Myelofibrosis Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Myelofibrosis, Primary Myelofibrosis (PMF)
RecruitingPhase 1
A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms
Polycythemia Vera (PV), Myelofibrosis (MF)
Active, not recruitingPhase 2
Extended Access of Momelotinib in Adults With Myelofibrosis
Primary Myelofibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Silverman, M.D. study director
Samus Therapeutics
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Samus Therapeutics company closure). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess Safety, Tolerability and Pharmacokinetics of PU-H71 (time frame: 24 weeks). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2022.