An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms

Sponsor
University of California, Irvine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT05123365
Collaborator
(none)
27
Enrollment
1
Location
3
Arms
46.4
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase I/II study evaluating the optimal dose of N-acetylcysteine (N-AC) in patients with myeloproliferative neoplasms (MPN).

Detailed Description

This is a phase I/II open-label clinical trial determining the optimal biological dose (OBD) of N-acetylcysteine in subjects with myeloproliferative neoplasms. These are subjects who have a diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
27 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms
Actual Study Start Date :
Jan 3, 2022
Anticipated Primary Completion Date :
Nov 15, 2022
Anticipated Study Completion Date :
Nov 15, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Level 1 (DL1)

Patients take N-Acetylcysteince 600 mg orally twice daily. This is the starting dose level for the study.

Drug: N-Acetylcysteine
Given PO
Other Names:
  • N-AC
  • Experimental: Dose Level 2 (DL2)

    Patients take N-Acetylcysteince 1200 mg orally twice daily. If DL1 is well tolerated, the next cohort will progress to this dose level.

    Drug: N-Acetylcysteine
    Given PO
    Other Names:
  • N-AC
  • Experimental: Dose Level 3 (DL3)

    Patients take N-Acetylcysteince 1800 mg orally twice daily. If DL2 is well tolerated, the next cohort will progress to this dose level.

    Drug: N-Acetylcysteine
    Given PO
    Other Names:
  • N-AC
  • Outcome Measures

    Primary Outcome Measures

    1. Optimal Biological Dose (OBD) of N-Acetylcysteine [From the start date of treatment until 7 days after completion of treatment or removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, up to 8 weeks.]

      Determination of the optimal biological dose (OBD) will be utilized to evaluate the safety and tolerability of N-AC as a treatment for patients with MPN. Optimal biological dose is defined as the therapeutic dose that possesses the highest efficacy probability while inducing acceptable toxicity

    2. Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS) [7 days prior to beginning treatment until end of treatment, average of 9 weeks.]

      MPN-SAF Total symptom score (MPN-TSS) is a validated tool to objectively measure the burden of symptoms associated with MPN. Baseline TSS will be defined as the average of the daily TSS of 7 consecutive days immediately prior to beginning N-AC. The end of study MPN-TSS will be defined as the average of the daily TSS of 7 consecutive days during week 8.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • ≥18 years of age

    • Have a diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) according to the 2016 WHO criteria

    • Has not taken interferon-alpha or a JAK inhibitor (such as ruxolitinib or fedratinib) for treatment of MPN in the past 28 days before enrollment.

    • May continue on current MPN treatment, including aspirin, hydroxyurea, or anagrelide. Therapeutic phlebotomies should continue per the patient's usual regimen.

    • Has not taken N-Acetylcysteine (N-AC) or preparations containing N-AC in the past 28 days before enrollment.

    • Baseline MPN-TSS score of ≥ 10 at the time of enrollment.

    • Peripheral blast count <10% during Screening.

    • Free of other active or metastatic malignancies other than localized skin cancer.

    • Amenable to blood draws and symptom assessments.

    • Agree to the use of contraceptives. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, should both use an effective contraception method during the study and continue to use contraception for 60 days after the last dose of study drug.

    Exclusion Criteria:
    • Eastern Cooperative Oncology Group (ECOG) questionnaire score of ≥3

    • Currently pregnant or planning on being pregnant within the study period.

    • Currently breastfeeding.

    • Known uncontrolled active viral or bacterial infection.

    • Significant impairment of major organ function defined as

    1. Serum creatinine clearance less than 50 ml/min (calculated with Cockroft-Gault formula).

    2. Bilirubin more than 1.5 mg/dl except for Gilbert's disease. ALT or AST more than 2X upper normal limit or has radiologic evidence of liver cirrhosis.

    3. Platelets < 100 × 10^9/L

    4. Hgb < 10 g/dL

    5. ANC < 0.75 × 10^9/L

    • Known history of allergic reaction to N-AC.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Chao Family Comprehensive Cancer Center, University of California, IrvineOrangeCaliforniaUnited States92868

    Sponsors and Collaborators

    • University of California, Irvine

    Investigators

    • Principal Investigator: Angela Fleischman, MD, PhD, Chao Family Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Angela G. Fleischman, Associate Professor, University of California, Irvine
    ClinicalTrials.gov Identifier:
    NCT05123365
    Other Study ID Numbers:
    • UCI 20-50 [HS# 2021-6930]
    • 2021-6930
    First Posted:
    Nov 17, 2021
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Angela G. Fleischman, Associate Professor, University of California, Irvine
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 24, 2022