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

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ClinicalTrials.gov Identifier: NCT05123365
Recruitment Status : Active, not recruiting
First Posted : November 17, 2021
Last Update Posted : January 24, 2022
Sponsor:
Information provided by (Responsible Party):
Angela G. Fleischman, University of California, Irvine

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

Condition or disease Intervention/treatment Phase
Myeloproliferative Neoplasm MPN Essential Thrombocythemia Polycythemia Vera Myelofibrosis Drug: N-Acetylcysteine Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms
Actual Study Start Date : January 3, 2022
Estimated Primary Completion Date : November 15, 2022
Estimated Study Completion Date : November 15, 2025


Arm Intervention/treatment
Experimental: Dose Level 1 (DL1)

Patients take N-Acetylcysteince 600 mg orally twice daily.

This is the starting dose level for the study.

Drug: N-Acetylcysteine
Given PO
Other Name: N-AC

Experimental: 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.

Drug: N-Acetylcysteine
Given PO
Other Name: N-AC

Experimental: 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.

Drug: N-Acetylcysteine
Given PO
Other Name: N-AC




Primary Outcome Measures :
  1. Optimal Biological Dose (OBD) of N-Acetylcysteine [ Time Frame: 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

  2. Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05123365


Locations
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United States, California
Chao Family Comprehensive Cancer Center, University of California, Irvine
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
Investigators
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Principal Investigator: Angela Fleischman, MD, PhD Chao Family Comprehensive Cancer Center
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Responsible Party: Angela G. Fleischman, Associate Professor, University of California, Irvine
ClinicalTrials.gov Identifier: NCT05123365    
Other Study ID Numbers: UCI 20-50 [HS# 2021-6930]
2021-6930 ( Other Identifier: University of California, Irvine )
First Posted: November 17, 2021    Key Record Dates
Last Update Posted: January 24, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Angela G. Fleischman, University of California, Irvine:
MPN
Myeloproliferative Neoplasm
Essential Thrombocytemia
Polycythemia Vera
Myelofibrosis
Additional relevant MeSH terms:
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Acetylcysteine
N-monoacetylcystine
Neoplasms
Polycythemia Vera
Primary Myelofibrosis
Myeloproliferative Disorders
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes