Overview

Addition of Nivolumab to Anti-CD-19 CAR-T Cells in Patients With Stable/Progressive DLBCL at Lymphodepletion

Status:
Recruiting

Trial end date:
2024-10-01

Target enrollment:
0

Participant gender:
All

Summary

Progression of DLBCL is the major obstacle for the success of chimeric antigen receptor-T cell (CAR-T) with approximately 60% of the patients relapsing in the first year, and 40% within 3 months, after infusion. While patient with DLBCL in Partial Response/Complete Response at lymphodepletion have a 1-year Progression Free Survival (PFS) of 60-80%, those with Stable Disease/Progressive Disease at time of lymphodepletion have a dismal PFS of 20-30%. Trials showed that better expansion of CAR-T cells, even in patients with a progressive disease, may overcome this grave prognosis and may result in better PFS

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Tel-Aviv Sourasky Medical Center

Treatments:

Nivolumab

Criteria

Inclusion Criteria:

1. Participant must be at least 18 years of age inclusive, at the time of signing the
informed consent.

2. DLBCL treated with CAR-T targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or
lisocabtagene maraleucel)

3. PD/SD by PET-CT on the day of lymphodepletion

4. Capable of giving signed informed consent

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

6. No active CRS or ICANS at time of nivolumab administration

Exclusion Criteria:

1. Hypersensitivity to checkpoints inhibitors

2. CRS grade 3 and above or ICANS any grade on days 0-5 following CAR-T

3. AST (Aspartate transaminase) or ALT (Alanine transaminase) over 3 times the upper
limit of normal (ULN) or total bilirubin over 3 times ULN

4. Serum creatinine over 1.5 times ULN or over 1.5 times baseline

5. History of or active autoimmune disease

6. Uncontrolled seizure activity and/or clinically evident progressive encephalopathy

7. Active diarrhea (more than 4 bowel movements per day)

8. Clinically significant uncontrolled illness

9. Active infection requiring antibiotics

10. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

11. Other active malignancy

12. Females only: Pregnant or breastfeeding