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

NCT05123365 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 20216930UCI 20-50
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Study Arms (3)

Dose Level 1 (DL1)

EXPERIMENTAL

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

Drug: N-Acetylcysteine

Dose Level 2 (DL2)

EXPERIMENTAL

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

Dose Level 3 (DL3)

EXPERIMENTAL

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

Interventions

N-Acetylcysteine DRUG

Given PO

Also known as: N-AC

Dose Level 1 (DL1); Dose Level 2 (DL2); Dose Level 3 (DL3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (2)

University of California, Irvine

Irvine, California, 92617, United States

RECRUITING

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Myeloproliferative Disorders; Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Angela Fleischman, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Fleischman, MD, PhD

CONTACT

(714) 456-8000; agf@hs.uci.edu

University of California Irvine Medical Center

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: November 17, 2021
• Study Start: January 3, 2022
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (2)