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

University of California Irvine (UCI)

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: N-Acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT05123365

UCI 20-50 (Other Identifier)

20216930

Details and patient eligibility

About

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

Full 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).

Enrollment: 27 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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27 participants in 3 patient groups

Dose Level 1 (DL1)

Experimental group

Description:

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

Treatment:

Drug: N-Acetylcysteine

Dose Level 2 (DL2)

Experimental group

Description:

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

Treatment:

Drug: N-Acetylcysteine

Dose Level 3 (DL3)

Experimental group

Description:

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

Treatment:

Drug: N-Acetylcysteine