N-Acetylcysteine for Lymphoma

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

9 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of N-AC when given in combination with Yescarta to people with lymphoma. This study will test different doses of N-AC to find the highest dose that causes few or mild side effects in participants.

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 N-Acetylcysteine generally safe for humans?

N-Acetylcysteine (NAC) has been used safely for many years to treat various conditions, including as an antidote for acetaminophen poisoning and to help with lung issues. Common side effects include nausea, vomiting, and diarrhea, but serious side effects are rare. ^{1 2 3 4 5}

Research Team

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Intravenous administration of oral N-acetylcysteine. [2019]