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

Primary Purpose

Myeloproliferative Neoplasm, MPN, Essential Thrombocythemia

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

N-Acetylcysteine

About this trial

This is an interventional treatment trial for Myeloproliferative Neoplasm focused on measuring MPN, Myeloproliferative Neoplasm, Essential Thrombocytemia, Polycythemia Vera, Myelofibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Chao Family Comprehensive Cancer Center, University of California, Irvine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose Level 1 (DL1)

Dose Level 2 (DL2)

Dose Level 3 (DL3)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT05123365

First Posted

November 5, 2021

Last Updated

January 6, 2023

Sponsor

University of California, Irvine

1. Study Identification

Unique Protocol Identification Number

NCT05123365

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 3, 2022 (Actual)

Primary Completion Date

July 31, 2024 (Anticipated)

Study Completion Date

November 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Irvine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose Level 1 (DL1)

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 2 (DL2)

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 3 (DL3)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

N-Acetylcysteine

Other Intervention Name(s)

N-AC

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Optimal Biological Dose (OBD) of N-Acetylcysteine

Description

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.

Title

Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)

Description

Time Frame

7 days prior to beginning treatment until end of treatment, average of 9 weeks.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Angela Fleischman, MD, PhD

Organizational Affiliation

Chao Family Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chao Family Comprehensive Cancer Center, University of California, Irvine

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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