CD19 positive

P2, N=50, Not yet recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

P1, N=55, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to slow enrollment and end of funding

Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

This study demonstrates a novel high-content and high-throughput screen can identify drugs to enhance CAR T cell activity. This and other high-content technologies will pave the way to develop clinical trials implementing rational drug plus CAR T cell combinatorial therapies. Importantly, the technique could also be repurposed for an array of basic and translational research applications where drugs are needed to modulate cell surface protein expression.

Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

P2, N=2, Active, not recruiting, University of Maryland, Baltimore | Trial completion date: Nov 2024 --> Aug 2027

P1, N=19, Recruiting, University Health Network, Toronto | Trial completion date: Nov 2025 --> May 2026 | Trial primary completion date: Nov 2024 --> Mar 2025

P1/2, N=0, Withdrawn, Zhujiang Hospital | N=70 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=30, Recruiting, Chinese PLA General Hospital | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=80, Not yet recruiting, Juventas Cell Therapy Ltd. | Initiation date: Oct 2023 --> Aug 2024

P2, N=60, Recruiting, Juventas Cell Therapy Ltd. | Trial primary completion date: Dec 2023 --> Jun 2024

P1/2, N=36, Recruiting, AO GENERIUM | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Feb 2025

P1, N=56, Active, not recruiting, Crystal Mackall, MD | Recruiting --> Active, not recruiting

© RSNA, 2024 Supplemental material is available for this article. See also the editorial by Bulte in this issue

P1, N=60, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jan 2026 --> Jun 2027 | Trial primary completion date: Jan 2025 --> Jun 2026

P1, N=44, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Mar 2025

P1, N=37, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.

P1, N=10, Recruiting, Institute of Hematology and Blood Transfusion, Czech Republic | Trial completion date: Jun 2028 --> Jun 2025 | Trial primary completion date: Jun 2027 --> Dec 2024

P1/2, N=90, Recruiting, Tanja Andrea Gruber | Not yet recruiting --> Recruiting

In summary, our work provides insights into the seminal use and behavior of CAR-macrophages which are derived from various sources of stem cells, while introducing a unique technology for CAR-macrophage manufacturing, all dedicated to the clinical translation of CAR-macrophages within the field of anticancer immunotherapies.

Here, we express an anti-CD19 εTRuC in primary γδ T cells that were expanded using zoledronate (Zol) or concanavalin A. We show that the resulting εTRuC γδ T cells were reprogrammed to better recognize CD19-positive B cell tumors and-in case of the Zol-expanded cells-a CD19-expressing colon adenocarcinoma-derived cell line in vitro...Finally, addition of vitamin C promoted the recovery of larger γδ T cell numbers after lentiviral transduction, as used for the expression of the εTRuC. In conclusion, the generation and use of γδ εTRuC T cells might be a new approach for cancer immunotherapy.

Tocilizumab and steroids are the major interventions for controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)...The combination of ruxolitinib and steroids effectively controlled severe CRS without impeding CAR-T cell expansion...Switching targets and eliminating residual CD7+ CAR-T cells in the blood are key points for patients who relapse after CD7+ CAR-T cell therapy. CAR-T cell therapies for AML have not been investigated in a large-scale cohort, except for CD19-positive AML with the AML1-ETO fusion gene.

P1, N=24, Recruiting, Chongqing Precision Biotech Co., Ltd

P1, N=116, Recruiting, AstraZeneca | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

P2, N=2, Active, not recruiting, University of Maryland, Baltimore | Trial completion date: Nov 2025 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Jun 2024

P1, N=36, Recruiting, C. Babis Andreadis | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

P2, N=104, Completed, Juno Therapeutics, a Subsidiary of Celgene | Active, not recruiting --> Completed | N=41 --> 104

P2, N=28, Not yet recruiting, Peking University People's Hospital; Fosun Kite Biotechnology Co., Ltd

P1, N=29, Recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University | Not yet recruiting --> Recruiting

P1, N=19, Completed, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Recruiting --> Completed | Trial completion date: Aug 2022 --> Nov 2023 | Trial primary completion date: Aug 2022 --> Nov 2023

SG299 is a CD8-targeted fusosome; a self-inactivating (SIN) lentiviral vector (LVV) pseudotyped with a CD8-targeted fusogen, which carries a transgene encoding a CD19-directed chimeric antigen receptor (CAR)...Finally, an assessment of donor-to-donor variability across five PBMC donors using a single lot of fusosome showed donor-specific variations in tumor control as measured by BLI but demonstrated a consistent protection from morbidity and mortality. Collectively, these studies demonstrate preclinical efficacy of our CD8/CD19CAR candidate, lot consistency and verify our ability to generate CD19-directed CAR T cells in vivo using a specifically targeted platform.

B-ALL pt received Dasatinib, Inotuzumab and CNS prophylaxis. Preparative conditioning regimen for these 4 patients were: Fludarabine-Cyclophosphamide (n=1), with Rituximab (n=2) and Rituximab with Nivolumab (n=1)... Reinfusion of varnimcabtagene autoleucel (IMN-003A) is feasible, safe and well tolerated. Preparative conditioning regimen for reinfusion needs personalization guided by CAR persistence, disease biology (CD20, PDL1 expression) and haematological reserve. After reinfusion, prolonged B cell aplasia was observed with 100% ORR at D+28 in evaluable pts.

(B) Cytotoxicity of MET-CAR against OCI-LY3 which is positive for MET but negative for CD19. E: T ratio is 10: 1.

Lymphodepletion consisted of cyclophosphamide 60mg/kg on day -6 and Fludarabine 25mg/m2/day on days -5 to -3...Two cases of CRS required no intervention, while the remaining cases received tocilizumab (n=4), steroids (n=2), and/or anakinra (n1)... As of 7/1/2023, a total of 13 patients were enrolled in Group A (NHL), and two patients were enrolled in Group B (B-ALL). Three patients in Group A withdrew consent or were withdrawn at the investigator's discretion due to new comorbid conditions before cell collection. Additionally, three patients were unable to receive CAR-T cell infusions due to disease progression, including two with Burkitt lymphoma.

Pts received lymphodepletion (LD) with cyclophosphamide 300 mg/m2/d and fludarabine 30 mg/m2/d for 3 days...Prior CD19 CAR T-cell product type was lisocabtagene maraleucel, n=4 (50%); axicabtagene ciloleucel, n= 3 (37%); or tisagenlecleucel, n=1...CONCLUSIONIn LBCL pts with disease relapse or progression after a first CD19 CAR T-cell therapy, we observed low response rates and lack of durable responses after treatment with the fully human scFv-bearing product JCAR021, prompting early study termination. Lower CAR T-cell expansion during manufacturing in CAR-exposed pts suggest pre-existing T-cell dysfunction as a potential mechanism of failure.

Similar results were obtained by combining Talazoparib and different PARP inhibitors with the alkylating agent cisplatin, indicating a class effect. Importantly, PBMC-derived T cells from healthy donors did not show any sign of DNA damage accumulation upon exposure to Lonca, Talazoparib and the combination. These data provide the rationale for future therapeutic strategies based on selective induction of DNA damage in neoplastic B cells in combination with DDR inhibition in aggressive MYC-positive B cell lymphoma.

Here, we present 6 patients with CD19-positive MPAL that are successfully treated with blinatumomab in combination with venetoclax and/or azacytidine in front line setting...The patient with BCR: : ABL1 received blinatumomab in combination with olverembatinib. Intrathecal (IT) chemotherapy with cytarabine and methotrexate was administered to central nervous system (CNS) as prophylaxis treatment... The results provide preliminary evidence of effective and safe treatment with blinatumomab and venetoclax combination as first-line therapy in MPAL resulting in the achievement of normal bone marrow function with less toxicity than using conventional chemotherapy.

P1, N=71, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=10, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Feb 2024 --> Dec 2025 | Trial primary completion date: Aug 2023 --> Dec 2024

P1, N=14, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

P1/2, N=51, Recruiting, MorphoSys AG | Phase classification: P1b/2 --> P1/2 | Trial completion date: Feb 2027 --> Oct 2027 | Trial primary completion date: May 2024 --> Nov 2024