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

Myelofibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05123365
• Other study ID #: 20216930
• Secondary ID: UCI 20-50
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 3, 2022
• Est. completion date: November 15, 2026

Study information

• Verified date: January 2024
• Source: University of California, Irvine
• Contact: Angela Fleischman, MD, PhD
• Phone: (714) 456-8000
• Email: agf[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: November 15, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Essential Thrombocythemia
• MPN
• Myelofibrosis
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• N-Acetylcysteine
Given PO

Locations

Country	Name	City	State
United States	University of California, Irvine	Irvine	California
United States	Chao Family Comprehensive Cancer Center, University of California, Irvine	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Irvine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Primary	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.	7 days prior to beginning treatment until end of treatment, average of 9 weeks.