A Study of Zelavespib (PU-H71) in Subjects With AP-MPN or BP-MPN

NCT05612633 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: PU-H71-OS-0204
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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 with ruxolitinib.

Conditions

Accelerated Phase MPN; Blast Phase MPN

Keywords

myeloproliferative neoplasm

Outcome Measures

Primary Outcomes (1)

• 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

  up to 6 months

Study Arms (1)

Oral zelavespib 100 mg

OTHER

Oral zelavespib 100 mg will be administered once daily

Drug: zelavespib

Interventions

zelavespib DRUG

Oral zelavespib 100 mg will be administered once daily

Oral zelavespib 100 mg

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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:

You may not qualify if:

• Known active liver disease, including viral hepatitis or cirrhosis
• 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
• 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

Sponsors & Collaborators

• Samus Therapeutics, Inc.: lead

MeSH Terms

Conditions

Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: November 10, 2022
• Study Start: June 15, 2022
• Primary Completion: December 15, 2023
• Study Completion: February 23, 2024
• Last Updated: November 10, 2022

Record last verified: 2022-11