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

NCT05385263 | Unknown Phase 2

• 1 other identifier: 0804-21
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response at 1 months after CAR-T infusion

  Complete or partial remission rate assessed by PET-CT (Positron Emission Tomography ) at 1 month after combination therapy with nivolumab and CAR-T.

  One month post CAR-T infusion

Secondary Outcomes (5)

• Overall survival at 1 year after CAR-T infusion and nivolumab

  One year post CAR-T infusion

• Duration of response

  One year post CAR-T infusion

• Cytokine release syndrome

  One year post CAR-T infusion

• Neurotoxicity

  One year post CAR-T infusion

• Hemophagocytic lymphohistiocytosis (HLH)

  One year post CAR-T infusion

Study Arms (1)

NIVOLUMAB

EXPERIMENTAL

All patients enrolled will be given nivolumab ( 3mg/kg IV) on day +5 Patients with CAR-T expansion\<100 cells/microL on day +7 will be given 1 additional dose of nivolumab (3mg/kg IV) on day +19 (two weeks after first dose of nivolumab).

Drug: Nivolumab Injection [Opdivo]

Interventions

Nivolumab Injection [Opdivo] DRUG

Nivolumab ( 3mg/kg IV) on day +5. If CAR-T expansion\<100 cells/microL on day +7 one additional dose of nivolumab (3mg/kg IV) will be given on day +19

NIVOLUMAB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
• DLBCL treated with CAR-T targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel)
• PD/SD by PET-CT on the day of lymphodepletion
• Capable of giving signed informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• No active CRS or ICANS at time of nivolumab administration

You may not qualify if:

• Hypersensitivity to checkpoints inhibitors
• CRS grade 3 and above or ICANS any grade on days 0-5 following CAR-T
• AST (Aspartate transaminase) or ALT (Alanine transaminase) over 3 times the upper limit of normal (ULN) or total bilirubin over 3 times ULN
• Serum creatinine over 1.5 times ULN or over 1.5 times baseline
• History of or active autoimmune disease
• Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
• Active diarrhea (more than 4 bowel movements per day)
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Other active malignancy
• Females only: Pregnant or breastfeeding

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

Study Sites (1)

Tel-Aviv Sourasky Medicak center / BMT Unit

Tel Aviv, 6423906, Israel

RECRUITING

Related Publications (1)

• Ram R, Amit O, Perry C, Herishanu Y, Avivi I, Sarid N, Apel A, Preis M, Aviv A, Shapira S, Shragai T, Joffe E, Shargian L, Herzog-Tsarfati K, Eylati N, Acria L, Fridberg G, Gold R, Glait-Santar C, Kay S, Gal-Rabinovich K, Rosenberg D, Setter-Marco N, Beyar-Katz O. Addition of Nivolumab Tailored by Expansion of CAR-T Cells in Patients with Stable/Progressive Large B Cell Lymphoma at Lymphodepletion-A Phase 2, Prospective Interventional Study. Transplant Cell Ther. 2024 Dec;30(12):1178-1188. doi: 10.1016/j.jtct.2024.09.024. Epub 2024 Oct 11.

  PMID: 39396632 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ron Ram, Prof.

  Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ron Ram, Prof

CONTACT

972-3-6947830; ronr@tlvmc.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: All patients enrolled to this study with DLBCL in SD/PD at time of lymphodepletion will be given nivolumab ( 3mg/kg IV) on day +5 Patients with CAR-T expansion\<100 cells/microL on day +7 will be given 1 additional dose of nivolumab (3mg/kg IV) on day +19 (two weeks after first dose of nivolumab).

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: May 23, 2022
• Study Start: May 11, 2022
• Primary Completion: April 1, 2024
• Study Completion: October 1, 2024
• Last Updated: May 26, 2022

Record last verified: 2022-04

Locations

IL (1)