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

Primary Purpose

Myeloproliferative Neoplasm, MPN, Essential Thrombocythemia

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
N-Acetylcysteine
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloproliferative Neoplasm focused on measuring MPN, Myeloproliferative Neoplasm, Essential Thrombocytemia, Polycythemia Vera, Myelofibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Chao Family Comprehensive Cancer Center, University of California, Irvine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Level 1 (DL1)

Dose Level 2 (DL2)

Dose Level 3 (DL3)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Optimal Biological Dose (OBD) of N-Acetylcysteine
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
Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)
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.

Secondary Outcome Measures

Full Information

First Posted
November 5, 2021
Last Updated
January 6, 2023
Sponsor
University of California, Irvine
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1. Study Identification

Unique Protocol Identification Number
NCT05123365
Brief Title
An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms
Official Title
An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 3, 2022 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
November 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloproliferative Neoplasm, MPN, Essential Thrombocythemia, Polycythemia Vera, Myelofibrosis
Keywords
MPN, Myeloproliferative Neoplasm, Essential Thrombocytemia, Polycythemia Vera, Myelofibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1 (DL1)
Arm Type
Experimental
Arm Description
Patients take N-Acetylcysteince 600 mg orally twice daily. This is the starting dose level for the study.
Arm Title
Dose Level 2 (DL2)
Arm Type
Experimental
Arm Description
Patients take N-Acetylcysteince 1200 mg orally twice daily. If DL1 is well tolerated, the next cohort will progress to this dose level.
Arm Title
Dose Level 3 (DL3)
Arm Type
Experimental
Arm Description
Patients take N-Acetylcysteince 1800 mg orally twice daily. If DL2 is well tolerated, the next cohort will progress to this dose level.
Intervention Type
Drug
Intervention Name(s)
N-Acetylcysteine
Other Intervention Name(s)
N-AC
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Optimal Biological Dose (OBD) of N-Acetylcysteine
Description
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
Time Frame
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.
Title
Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)
Description
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.
Time Frame
7 days prior to beginning treatment until end of treatment, average of 9 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 Serum creatinine clearance less than 50 ml/min (calculated with Cockroft-Gault formula). 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. Platelets < 100 × 10^9/L Hgb < 10 g/dL ANC < 0.75 × 10^9/L Known history of allergic reaction to N-AC.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Fleischman, MD, PhD
Organizational Affiliation
Chao Family Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chao Family Comprehensive Cancer Center, University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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