Essential Thrombocythemia, MPN, Myelofibrosis, Myeloproliferative Neoplasm, Polycythemia Vera
Conditions
Keywords
MPN, Myeloproliferative Neoplasm, Essential Thrombocytemia, Polycythemia Vera, Myelofibrosis
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).
Interventions
DRUGN-Acetylcysteine
Given PO
Sponsors
University of California, Irvine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optimal Biological Dose (OBD) of N-Acetylcysteine | 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. | 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 |
| Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS) | 7 days prior to beginning treatment until end of treatment, average of 9 weeks. | 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. |
Countries
United States
Contacts
CONTACTAngela Fleischman, MD, PhD
CONTACTUniversity of California Irvine Medical Center
PRINCIPAL_INVESTIGATORAngela Fleischman, MD, PhD
Chao Family Comprehensive Cancer Center
Outcome results
None listed