Clinical trial NCT05123365: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myeloproliferative Neoplasm
MPN
Essential Thrombocythemia
Polycythemia Vera
Myelofibrosis
Keywords: MPN
Myeloproliferative Neoplasm
Essential Thrombocytemia
Polycythemia Vera
Myelofibrosis
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
First posted: 2021-11-17
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Optimal Biological Dose (OBD) of N-Acetylcysteine
timeFrame: 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.
measure: Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)
timeFrame: 7 days prior to beginning treatment until end of treatment, average of 9 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center, University of California, Irvine
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Angela Fleischman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: