N-Acetylcysteine for Lymphoma

Not currently recruiting at 6 trial locations

Overseen By Alison Moskowitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Allergy to N-AC

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of combining N-Acetylcysteine (N-AC) with Yescarta, a treatment for lymphoma, a type of blood cancer. Researchers aim to find the highest dose of N-AC that causes few or mild side effects when used with Yescarta. The trial includes three groups, each receiving different doses of N-AC to determine which is most effective without causing excessive side effects. Individuals with lymphoma who are set to receive Yescarta and can perform daily activities without major difficulty may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that N-Acetylcysteine (NAC) is generally safe for use. Often taken as a supplement, NAC has been studied for various health conditions. Reviews of clinical trials indicate that NAC is safe and may even extend lifespan. It has a strong safety record and is well-tolerated by most individuals.

Studies have used NAC to support treatments like CAR T-cell therapy for cancer patients, and these studies did not report any serious safety issues. Additionally, NAC helps protect cells from damage caused by oxidative stress, an imbalance that can harm cells.

This trial tests NAC with Yescarta, a treatment for lymphoma. Since NAC is in the early stages of testing for this use, researchers are still determining the best dose and monitoring for any side effects. However, existing evidence suggests that NAC is likely to be well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about N-Acetylcysteine for treating lymphoma because it offers a novel approach by potentially enhancing the body's antioxidant defenses. Unlike traditional chemotherapy and radiation treatments, which target cancer cells more directly but can also damage healthy cells, N-Acetylcysteine works by replenishing glutathione levels, a powerful antioxidant, which might help protect healthy cells and reduce side effects. This unique mechanism could make it a valuable addition to existing lymphoma therapies by possibly improving patient outcomes and quality of life.

What evidence suggests that N-Acetylcysteine might be an effective treatment for lymphoma?

Research suggests that N-Acetylcysteine (NAC) might enhance the effects of CAR T-cell therapy in treating lymphoma. CAR T-cells are special immune cells used to fight cancer. One study showed that NAC helped these cells last longer in patients. Another study found that NAC can protect lymphoma cells from oxidative stress, a harmful condition that can damage cells. Additionally, NAC increased the lifespan of mice with a certain genetic issue and lowered their chances of developing lymphoma. This trial will explore the effects of NAC at different dose levels: participants in Cohort 1 will receive 25% of the target dose, Cohort 2 will receive 50%, and Cohort 3 will receive 100% if no dose-limiting toxicities occur at lower doses. These findings suggest that NAC could improve lymphoma treatment outcomes. ^{2 3 6 7 8}

Who Is on the Research Team?

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with lymphoma who are about to receive Yescarta (CAR T-cell therapy). They must be over 18, have a performance status that allows daily activity, and their blood counts and organ functions need to meet specific levels. People allergic to N-Acetylcysteine cannot participate.

Inclusion Criteria

I will be treated with axicabtagene ciloleucel for my lymphoma.

Patients must have adequate end organ function to be eligible for this study as defined by the following criteria: ECOG performance status 0-2, Hematologic function with ANC ≥ 1000, Hgb ≥ 8, Plt ≥ 50k unless there is disease related hematologic toxicity, Renal function with CrCr ≥ 40 ml/min or Cr ≤ 1.5 x ULN, Hepatic function with ALT/AST ≤ 2.5 x ULN, TBili ≤ 1.5 x ULN.

Exclusion Criteria

Patients with known allergy to N-AC

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-Acetylcysteine in combination with Yescarta, with dose escalation to determine the maximum tolerated dose

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetylcysteine

Trial Overview

The study is testing the safety of different doses of N-Acetylcysteine (N-AC) when given alongside Yescarta in lymphoma patients. The goal is to find the highest dose of N-AC that has few or mild side effects.

How Is the Trial Designed?

Group I: Participants with Lymphoma, Cohort 3 Experimental Treatment 1 Intervention

The third cohort in the study will be treated at 100% of that target dose level only if no DLTs are seen at lower doses.

Group II: Participants with Lymphoma, Cohort 2 Experimental Treatment 1 Intervention

The second cohort in the study will be treated at 50% of that target dose level

Group III: Participants with Lymphoma, Cohort 1 Experimental Treatment 1 Intervention

The first dose escalation cohort in the study will be treated at 25% of that target dose level

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study involving 12 hemodialysis patients, intravenous administration of 2 g of N-acetylcysteine (NAC) over 3 hours was found to be safe, with no observed side effects during the six dialysis sessions.

NAC reached a steady state concentration after the fourth infusion, indicating effective pharmacokinetics in dialysis patients, with a significant dialytic clearance of 5.52 l/h.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. Soldini, D., Zwahlen, H., Gabutti, L., et al.[2018]

N-Acetylcysteine is effective as a mucolytic agent for chronic bronchitis and as an antidote for paracetamol poisoning, with peak plasma concentrations achieved within 1 to 2 hours after oral doses of 200 to 400 mg.

While it has significant therapeutic benefits, common side effects include nausea, vomiting, and diarrhea, and it may interact with other drugs, particularly paracetamol and certain anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. Holdiness, MR.[2022]

A study of 76 patients receiving intravenous N-acetylcysteine (originally an oral preparation) showed that this method has limited adverse effects, with only 5.3% experiencing any reactions, none of which were serious.

The intravenous route provides a valuable alternative for administering N-acetylcysteine, especially in situations where oral intake is not feasible, and the deaths observed in the study were not linked to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous administration of oral N-acetylcysteine. Yip, L., Dart, RC., Hurlbut, KM.[2019]

N-acetylcysteine (NAC) effectively increases plasma cysteine and glutathione levels, particularly at a dose of 70 mg/kg, which also correlates with improved handgrip exercise performance.

Higher doses of NAC (140 mg/kg) can lead to significant gastrointestinal adverse reactions, suggesting that lower doses may be safer and still effective for enhancing thiol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. Ferreira, LF., Campbell, KS., Reid, MB.[2021]

N-acetylcysteine (NAC) has a wide range of clinical applications, including treatment for paracetamol overdose and various disorders, due to its antioxidative properties and ability to restore impaired cellular components.

NAC's unique effectiveness is likely due to its ability to reduce disulfide bonds in proteins, which alters their structure and function, although more research is needed to fully understand its mechanisms and how it interacts with cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. Samuni, Y., Goldstein, S., Dean, OM., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8719286/

The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC ...

NAC was effective from 6 months onwards, suggesting that the preventive effects of NAC are slow to develop but then progress, and are sustained with regular ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636725003914

Infusional N-Acetylcysteine Enhances CAR T Cell ...

Preliminary correlative analysis indicates that NAC substantially increased CAR-T persistence at 1 week (29.7% vs. 4.6% of all viable cells, p = 0.026) in ...

3.

cell.com

cell.com/cell-reports/fulltext/S2211-1247(23)00972-5

A MYC-controlled redox switch protects B lymphoma cells ...

We report that high MYC expression stimulates proliferation and protects B lymphoma cells from apoptosis under normal oxidative stress levels.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1568786406001200

Antioxidant N-acetyl cysteine reduces incidence and ...

We found that oral NAC administration significantly increased the lifespan of Atm deficient mice and reduced both the incidence and multiplicity of lymphoma.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9563555/

NAC, NAC, Knockin' on Heaven's door

NAC-cultured T cells were 33-fold higher than T cells cultured without NAC. NAC enhances the therapeutic outcomes for adoptive cell transfer therapy by ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC

Analysis of the data showed that NAC can decrease the decline in lung function in patients with IPF, related to the reduction in the decline in forced vital ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8211525/

N-Acetylcysteine: A Review of Clinical Usefulness (an Old ...

A meta-analysis of prospective clinical trials reviewing NAC-treated and placebo-treated groups showed NAC to be safe and prolonged the survival ...

8.

jn.nutrition.org

jn.nutrition.org/article/S0022-3166(22)09041-1/pdf

Antioxidants Suppress Lymphoma and Increase Longevity in ...

We review these findings, mainly focusing on the effect of N-acetyl cysteine, which is known as a safe and efficient drug and nutritional supplement. J. Nutr.