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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05081479

Collaborator

(none)

Enrollment

Location

Arms

34.4

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: N-Acetylcysteine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 8, 2021

Anticipated Primary Completion Date :

Oct 21, 2024

Anticipated Study Completion Date :

Oct 21, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants with Lymphoma, Cohort 1 The first dose escalation cohort in the study will be treated at 25% of that target dose level	Drug: N-Acetylcysteine 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. Other Names: N-AC
Experimental: Participants with Lymphoma, Cohort 2 The second cohort in the study will be treated at 50% of that target dose level	Drug: N-Acetylcysteine 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. Other Names: N-AC
Experimental: Participants with Lymphoma, Cohort 3 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 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. Other Names: N-AC

Arm

Intervention/Treatment

Experimental: Participants with Lymphoma, Cohort 1

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

Drug: N-Acetylcysteine

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.

Other Names:

N-AC

Experimental: Participants with Lymphoma, Cohort 2

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

Drug: N-Acetylcysteine

Other Names:

N-AC

Experimental: Participants with Lymphoma, Cohort 3

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

Other Names:

N-AC

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of N-AC [Up to 1 year]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.