Accelerated Phase MPNPhase 2AP-MPNNCT05612633
A Study of Zelavespib (PU-H71) in Subjects With AP-MPN or BP-MPN
A Phase 2 study testing zelavespib in people with Accelerated Phase MPN and Blast Phase MPN, run by Samus Therapeutics, Inc..
Trial summary
This is a multicenter, Phase 2 Simon 2-Stage study designed to assess the safety, tolerability, PK, and efficacy of oral zelavespib (PU-H71) administered daily in adults with accelerated phase (10% to 19% blasts in peripheral or bone marrow) myeloproliferative neoplasm, with or without ongoing concomitant treatment… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Accelerated Phase MPN, Blast Phase MPN
- What is being tested?
- zelavespib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Jun 2022to 23 Feb 2024
- Phase
- Phase 2
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Able to provide signed informed consent and willing to comply with the requirements and restrictions listed in the informed consent form and in this protocol
- Aged ≥ 18 years
- Confirmed diagnosis of accelerated phase (10% to 19% blasts in peripheral blood or bone marrow) MPN arising on the background of previous PMF, PV, or ET
- Patients taking ruxolitinib must have been taking it for at least 3 months, with a stable dose at least 1 month before Cycle 1 Day 1
- Eastern Cooperative Oncology Group (ECOG) performance status of 1 to 2
- Acceptable organ function at screening, defined by the following criteria:
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- absolute neutrophil count (ANC) ≥ 500/µL
- platelet count ≥ 50,000/µL
- alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2 × the upper limit of normal (ULN )
- total serum bilirubin ≤ 1.5 × ULN
- creatinine clearance > 25 mL/min/1.73 m2 based on the Cockcroft-Gault equation
- Women of childbearing potential (defined as premenopausal or within 2 years of the onset of menopause, and not surgically sterile) must meet both the following criteria:
- negative urine or serum pregnancy test at screening and within 72 hours before the first dose of zelavespib
- agree to use one of the following acceptable method of highly effective contraception for the duration of the study and for 13 weeks after the final dose of study treatment
- Men must agree to the following requirements:
- men who are sexually active with women of childbearing potential must agree to the following requirements for the duration of their participation in the study and for 13 weeks after the final dose of study treatment: i. if the method of contraception is abstinence from penile vaginal intercourse as a usual and preferred lifestyle (abstinent on a long-term and persistent basis), men must agree to remain abstinent ii. if having penile vaginal intercourse with a nonpregnant, non-breastfeeding woman of childbearing potential, men must use a male condom, and their female partner must use a highly effective contraceptive method with a failure rate < 1% per year iii. men with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration iv. men must refrain from donating sperm
Who cannot join
- Known active liver disease, including viral hepatitis or cirrhosis
- Known or suspected infection with human immunodeficiency virus (HIV) or other active infection requiring acute or chronic treatment with systemic antibiotics (conditions requiring topical antibiotics are not exclusionary)
- Positive for HIV 1 or 2, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies at screening
- Previous treatment with a hypomethylating agent
- Corrected QT interval using Fridericia's formula (QTcF) > 480 ms at screening or baseline ECG based on the median value of ECGs
- Personal or family history of long QT syndrome or taking any medication within 1 week or 5 half-lives (whichever is longer) before Cycle 1 Day 1 that carries a risk of Torsades de Pointes
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- Left ventricular ejection fraction ≤ 50% or below the institution's lower limit of normal (whichever is lower) by echocardiogram or multigated acquisition (MUGA) scan
- Coronary artery disease with an ischemic event within 6 months before screening
- History of a second primary malignancy within 6 months before screening that requires treatment with systemic antineoplastic agents, except for the following, if appropriately treated and considered cured: Stage 1 endometrial cancer, surgically treated cervical or prostate carcinoma, and nonmelanoma skin cancer Note: Subjects who are receiving adjuvant or preventive therapy for indolent cancers may be eligible, and the investigator should discuss with the medical monitor.
- Any significant uncontrolled medical condition, as determined by the investigator, within 6 months before screening
- Planned use of antineoplastic agents (chemotherapy or cytotoxic drugs), immunotherapy, experimental therapy, or biologic therapy for treatment of MPN, with the exception of ruxolitinib
- Use of systemic corticosteroids (ie, prednisone > 20 mg/day or equivalent within 2 weeks before Cycle 1 Day 1
- Planned or current use of strong cytochrome P450 (CYP)3A4/5, CYP2D6, or CYP2C19 inhibitors or inducers within 1 week or 5 half-lives (whichever is longer, for a maximum of 4 weeks) before Cycle 1 Day 1
- Planned or current use of herbal preparations/medications within 7 days before Cycle 1 Day 1
- Previous exposure to zelavespib (PU-H71)
- Uncontrolled diabetes mellitus, in the opinion of the investigator
- Any other condition or laboratory abnormality or receiving any other treatment that, in the opinion of the investigator, may increase the risk associated with study participation or that may interfere with interpretation of the study results
- Active ocular condition (eg, ocular inflammatory disease that, in the opinion of the investigator, may worsen during the course of the study, or a history or anticipation of major ocular surgery (eg, cataract extraction or other intraocular surgery) during the study
- Currently pregnant or breastfeeding, or planning to become pregnant
- History of gastrointestinal surgery or current gastrointestinal condition that could affect the absorption of oral medication
About this study
Official title: A Phase 2 Open-label Study of Zelavespib (PU-H71) in Subjects With Accelerated Phase Myeloproliferative Neoplasm (AP MPN) or Blast Phase Myeloproliferative Neoplasm
This is a multicenter, Phase 2 Simon 2-Stage study designed to assess the safety, tolerability, PK, and efficacy of oral zelavespib (PU-H71) administered daily in adults with accelerated phase (10% to 19% blasts in peripheral or bone marrow) myeloproliferative neoplasm, with or without ongoing concomitant treatment with ruxolitinib.
Read the detailed description
Oral zelavespib 1501050 mg will be administered once daily (QD), in the morning ≥ 1 hour before eating breakfast, for each day of a 21-day cycle, for 6 cycles. Subjects who derive clinical benefit may continue treatment until disease progression, unacceptable toxicity, death, or study termination.
In Stage 1, up to 2317 subjects will be enrolled and will complete 6 cycles of treatment. If fewer than 2 subjects achieve <CR?/PR?/CBR?/PBR?> in Stage 1, the trial will be stopped for futility. If 2 or more subjects achieve <CR?/PR?/CBR?/PBR?>a response , an additional 33 subjects will be enrolled, enrollment will begin in Stage 2 for a total of 56 subjects. . If fewer than 2 subjects achieve a response in Stage 1, the trial will be stopped for futility.
In Cycle 1, subjects will attend 3 clinic visits (Day 1, Day 8, and Day 15) and will be contacted by phone by the site at approximately Day 4 . In subsequent cycles, subjects will attend a clinic visit on Day 1 onlyand will be contacted by phone on Days 8 and 15 so the site staff can inquire about changes in concomitant medications and potential AEs. On days of clinic visits, subjects will arrive at the clinic without eating anything in the morning or taking the study drug. Predose biological samples will be collected for safety laboratory tests and other clinical assessments, and subjects will undergo physical examinations and ECGs. Subjects will receive the study drug at the clinic and at least 1 hour after dosing, breakfast will be provided. On some clinic days, subjects may be required to remain in the clinic for up to 8 hours for additional ECGs and collection of samples for PK testing.
Each subject will participate in the study for approximately 6.5 months , which includes a 28-day screening period, 6 cycles of treatment, and a final follow-up visit 30 days after the final dose of study treatment.
- Conditions
- Accelerated Phase MPN, Blast Phase MPN
- Being tested
- zelavespib
- Keywords
- myeloproliferative neoplasm
- Medical subject headings
- Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zelavespibDrug
Oral zelavespib 100 mg will be administered once daily
| Study group | Role | What they receive |
|---|---|---|
| Oral zelavespib 100 mg | Other | Oral zelavespib 100 mg will be administered once daily Receives: Drug: zelavespib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the MTD and safety of PU-H71 in subjects with AP-MPN and BP-MPN
Assess the safety profile by measuring Incidence and severity of adverse events (AEs), changes in physical examinations, electrocardiograms (ECGs), vital signs, and clinical laboratory evaluations
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2022
- Study start15 Jun 2022 (estimated)
- Primary completion15 Dec 2023 (estimated)
- Study completion23 Feb 2024 (estimated)
Why it stopped: Samus Therapeutics Closure
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Accelerated Phase MPNStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- In Stage 1, up to 2317 subjects will be enrolled and will complete 6 cycles of treatment. If fewer than 2 subjects achieve \<CR?/PR?/CBR?/PBR?\> in Stage 1, the trial will be stopped for futility. If 2 or more subjects achieve \<CR?/PR?/CBR?/PBR?\>a response , an additional 33 subjects will be enrolled, enrollment will begin in Stage 2 for a total of 56 subjects.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05612633
- Sponsor's protocol ID
- PU-H71-OS-0204
- Acronym
- AP-MPN
- Status last verified
- Nov 2022
- First submitted
- 4 Oct 2021
- Last updated
- 10 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-label Study of Zelavespib (PU-H71) in Subjects With Accelerated Phase Myeloproliferative Neoplasm (AP MPN) or Blast Phase Myeloproliferative Neoplasm
- ClinicalTrials.gov ID
- NCT05612633
- Acronym / sponsor ID
- AP-MPN / PU-H71-OS-0204
- Conditions
- Accelerated Phase MPN, Blast Phase MPN
- Keywords
- myeloproliferative neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Samus Therapeutics Closure
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Samus Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jun 2022 (estimated)
- Primary completion
- 15 Dec 2023 (estimated)
- Study completion
- 23 Feb 2024 (estimated)
- First posted
- 10 Nov 2022 (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 2 Simon 2-Stage study designed to assess the safety, tolerability, PK, and efficacy of oral zelavespib (PU-H71) administered daily in adults with accelerated phase (10% to 19% blasts in peripheral or bone marrow) myeloproliferative neoplasm, with or without ongoing concomitant treatment with ruxolitinib.
Detailed description
Oral zelavespib 1501050 mg will be administered once daily (QD), in the morning ≥ 1 hour before eating breakfast, for each day of a 21-day cycle, for 6 cycles. Subjects who derive clinical benefit may continue treatment until disease progression, unacceptable toxicity, death, or study termination.
In Stage 1, up to 2317 subjects will be enrolled and will complete 6 cycles of treatment. If fewer than 2 subjects achieve <CR?/PR?/CBR?/PBR?> in Stage 1, the trial will be stopped for futility. If 2 or more subjects achieve <CR?/PR?/CBR?/PBR?>a response , an additional 33 subjects will be enrolled, enrollment will begin in Stage 2 for a total of 56 subjects. . If fewer than 2 subjects achieve a response in Stage 1, the trial will be stopped for futility.
In Cycle 1, subjects will attend 3 clinic visits (Day 1, Day 8, and Day 15) and will be contacted by phone by the site at approximately Day 4 . In subsequent cycles, subjects will attend a clinic visit on Day 1 onlyand will be contacted by phone on Days 8 and 15 so the site staff can inquire about changes in concomitant medications and potential AEs. On days of clinic visits, subjects will arrive at the clinic without eating anything in the morning or taking the study drug. Predose biological samples will be collected for safety laboratory tests and other clinical assessments, and subjects will undergo physical examinations and ECGs. Subjects will receive the study drug at the clinic and at least 1 hour after dosing, breakfast will be provided. On some clinic days, subjects may be required to remain in the clinic for up to 8 hours for additional ECGs and collection of samples for PK testing.
Each subject will participate in the study for approximately 6.5 months , which includes a 28-day screening period, 6 cycles of treatment, and a final follow-up visit 30 days after the final dose of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- In Stage 1, up to 2317 subjects will be enrolled and will complete 6 cycles of treatment. If fewer than 2 subjects achieve <CR?/PR?/CBR?/PBR?> in Stage 1, the trial will be stopped for futility. If 2 or more subjects achieve <CR?/PR?/CBR?/PBR?>a response , an additional 33 subjects will be enrolled, enrollment will begin in Stage 2 for a total of 56 subjects.
| Arm | Type | Receives |
|---|---|---|
| Oral zelavespib 100 mg | Other | Drug: zelavespibOral zelavespib 100 mg will be administered once daily |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Able to provide signed informed consent and willing to comply with the requirements and restrictions listed in the informed consent form and in this protocol
- Aged ≥ 18 years
- Confirmed diagnosis of accelerated phase (10% to 19% blasts in peripheral blood or bone marrow) MPN arising on the background of previous PMF, PV, or ET
- Patients taking ruxolitinib must have been taking it for at least 3 months, with a stable dose at least 1 month before Cycle 1 Day 1
- Eastern Cooperative Oncology Group (ECOG) performance status of 1 to 2
Key exclusion criteria (20 listed)
- Known active liver disease, including viral hepatitis or cirrhosis
- Known or suspected infection with human immunodeficiency virus (HIV) or other active infection requiring acute or chronic treatment with systemic antibiotics (conditions requiring topical antibiotics are not exclusionary)
- Positive for HIV 1 or 2, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies at screening
- Previous treatment with a hypomethylating agent
- Corrected QT interval using Fridericia's formula (QTcF) > 480 ms at screening or baseline ECG based on the median value of ECGs
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 |
|---|---|---|
| zelavespibOral zelavespib 100 mg will be administered once daily | Drug | Oral zelavespib 100 mg |
Primary outcome
Determine the MTD and safety of PU-H71 in subjects with AP-MPN and BP-MPN
Time frame: up to 6 months
Assess the safety profile by measuring Incidence and severity of adverse events (AEs), changes in physical examinations, electrocardiograms (ECGs), vital signs, and clinical laboratory evaluations
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2022.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zelavespib in people with Accelerated Phase MPN and Blast Phase MPN, run by Samus Therapeutics, Inc..
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 16 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: withdrawn, as of the sponsor's last update on 10 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Determine the MTD and safety of PU-H71 in subjects with AP-MPN and BP-MPN (time frame: up to 6 months). 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 10 Nov 2022.