A Study of N-Acetylcysteine (N-AC)in People Receiving CAR T-cell Therapy for Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase I Study of N-Acetylcysteine to Optimize Metabolic Tumor Microenvironment in CD19 CAR T-cell Therapy in Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: N-Acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be 18 years of age or older Patients who will receive axicabtagene ciloleucel for treatment of 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Lymphoma, Cohort 1<br>The first dose escalation cohort in the study will be treated at 25% of that target dose level | Drug: N-Acetylcysteine<br>* N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.<br>* Other names: N-AC;|
| Experimental: Participants with Lymphoma, Cohort 2<br>The second cohort in the study will be treated at 50% of that target dose level | Drug: N-Acetylcysteine<br>* N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.<br>* Other names: N-AC;|
| Experimental: Participants with Lymphoma, Cohort 3<br>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. | Drug: N-Acetylcysteine<br>* N-AC infusion will begin the day before CAR T cell infusion and continuously infused over 24-hours for 14 days or until time of discharge whichever is earlier. Interruptions of N-AC infusion for medical reasons are permissible. The dose for patients <45kg will be adjusted to weight based dosing.<br>* Other names: N-AC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of N-AC | This is a phase 1 dose escalation and expansion study to determine the maximum tolerated dose and recommended phase 2 dose of NAC given in conjunction with axicabtagene ciloleucel. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-AC, N-Acetylcysteine, Lymphoma, CD19 CAR T-cell Therapy, 21-386, Memorial Sloan Kettering Cancer Center