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

NCT ID: NCT05123365

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-03
• Study Completion Date: 2026-11-15

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).

Conditions

Myeloproliferative Neoplasm; MPN; Essential Thrombocythemia; Polycythemia Vera; Myelofibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level 1 (DL1)

Patients take N-Acetylcysteince 600 mg orally twice daily.

This is the starting dose level for the study.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

Given PO

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

Given PO

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.

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

Given PO

Interventions

N-Acetylcysteine

Given PO

Intervention Type: DRUG

Other Intervention Names

N-AC

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Angela G. Fleischman

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angela Fleischman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Locations

University of California, Irvine

Irvine, California, United States

Site Status: RECRUITING

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Angela Fleischman, MD, PhD

Role: CONTACT

agf@hs.uci.edu

(714) 456-8000

University of California Irvine Medical Center

Role: CONTACT

Facility Contacts

Angela G Fleischman, MD PhD

Role: primary

agf@uci.edu

(949) 999-2400

Other Identifiers

UCI 20-50

Identifier Type: OTHER

Identifier Source: secondary_id

20216930

Identifier Type: -

Identifier Source: org_study_id