NCT04381741: CICPD

CD19 CAR-T Expressing IL7 and CCL19 Combined With PD1 mAb for Relapsed or Refractory Diffuse Large B Cell Lymphoma

Status unknown Phase 1 Last updated 6 February 2023

What this trial tests

Phase 1 trial testing CD19-7×19 CAR-T plus PD1 monoclonal antibody in Diffuse Large B-cell Lymphoma in 24 participants. Status unknown.

Timeline

18 June 2020

Primary endpoint
1 September 2023

1 September 2023

Quick facts

Lead sponsor	Second Affiliated Hospital, School of Medicine, Zhejiang University
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	18 June 2020
Primary completion	1 September 2023
Estimated completion	1 September 2023
Sites	1 location across China

Drugs / interventions tested

• CD19-7×19 CAR-T plus PD1 monoclonal antibody — full drug profile →

Conditions studied

• Diffuse Large B-cell Lymphoma — all drugs for Diffuse Large B-cell Lymphoma →

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Who can join

Adults 18 to 75, any sex, with Diffuse Large B-cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for 35% of lymphoma. Chimeric antigen receptor T cell (CAR-T) therapy is a new method to treat DLBCL. KTE-C19, published in the New England Medical Journal in December 2017, was used to treat relapsed and refractory B-cell lymphoma. One year of treatment for 111 patients, the total response rate was 82%, and the complete remission rate was 54%. However, a large number of clinical studies have shown that about 20% of patients with B-ALL and 50% of patients with B-NHL cannot achieve complete remission (CR) after CD19-CAR-T treatment. Targeting tumor microenvironment is an important new method to overcome the drug resistance of CAR-T cells. In this study, IL-7 and CCL19 were connected on the basis of traditional second generation CD19 CAR-T cells to construct novel fourth generation CAR-T cells, which can promote the infiltration, accumulation and survival of CAR-T cells in lymphoma tissue, and further enhance the anti-tumor effect of traditional CAR-T cells. At the same time, combined with four generations of CAR-T cells and PD1 monoclonal antibody, PD1 / PDL1 signal pathway was blocked, anti-tumor effect of CAR-T was improved, and immune response and long-term remission rate of DLBCL were improved.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Exploring treatment options in cancer: Tumor treatment strategies.
   Liu B, Zhou H, Tan L, Siu KTH, et al · · 2024 · cited 536× · PMID 39013849 · DOI 10.1038/s41392-024-01856-7
2. Recent advances in CAR-T cell engineering.
   Huang R, Li X, He Y, Zhu W, et al · · 2020 · cited 274× · PMID 32616000 · DOI 10.1186/s13045-020-00910-5
3. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
4. Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies.
   Ruella M, Korell F, Porazzi P, Maus MV. · · 2023 · cited 123× · PMID 37907724 · DOI 10.1038/s41573-023-00807-1
5. CAR T-Cell Therapy in Hematological Malignancies.
   Haslauer T, Greil R, Zaborsky N, Geisberger R. · · 2021 · cited 115× · PMID 34445701 · DOI 10.3390/ijms22168996
6. Engineered Cytokine Signaling to Improve CAR T Cell Effector Function.
   Bell M, Gottschalk S. · · 2021 · cited 108× · PMID 34177932 · DOI 10.3389/fimmu.2021.684642
7. Next generations of CAR-T cells - new therapeutic opportunities in hematology?
   Tomasik J, Jasiński M, Basak GW. · · 2022 · cited 98× · PMID 36389658 · DOI 10.3389/fimmu.2022.1034707
8. The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy.
   Wang C, Kong L, Kim S, Lee S, et al · · 2022 · cited 78× · PMID 36142322 · DOI 10.3390/ijms231810412