Rituxan (rituximab)

P2/3, N=210, Not yet recruiting, University of Birmingham | Trial completion date: Oct 2032 --> May 2033 | Initiation date: Oct 2023 --> May 2024 | Trial primary completion date: Oct 2030 --> May 2031

P=N/A, N=10000, Recruiting, Seoul National University Hospital | Trial completion date: Jun 2025 --> Jun 2030 | Trial primary completion date: Dec 2024 --> Dec 2029

P3, N=1152, Completed, Universität des Saarlandes | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jan 2024 | Trial primary completion date: May 2025 --> Jan 2024

P2, N=33, Completed, Peking Union Medical College Hospital | Recruiting --> Completed | Trial completion date: Aug 2023 --> Mar 2024 | Trial primary completion date: Aug 2022 --> Mar 2024

P3, N=250, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion.

P1, N=50, Suspended, University of Washington | Recruiting --> Suspended

P1/2, N=113, Active, not recruiting, Acerta Pharma BV | Phase classification: P1 --> P1/2

P2/3, N=260, Recruiting, Merck Sharp & Dohme LLC | N=420 --> 260 | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.

Historically, B and T cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab or ofatumumab...In the treatment of cancer, chimeric antigen receptor (CAR) T cell therapy and T cell engagers (TCE) that recruit T cells to induce B cell cytotoxicity have delivered promising results for anti-CD19 CAR T cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab or epcoritamab. Limited evidence suggests that anti-CD19 CAR T cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B-T cell collaboration toward overcoming rituximab-resistant AID.

P3, N=612, Recruiting, Epizyme, Inc. | Trial completion date: Mar 2029 --> Apr 2032 | Trial primary completion date: Mar 2026 --> Sep 2029

P2, N=40, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting

Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival...Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

In 2019, several randomized, placebo-controlled trials were completed that demonstrated the remarkable efficacy of eculizumab (anti-C5 complement inhibitor), inebilizumab (anti-CD19 B-cell-depleting agent), and satralizumab (anti-interleukin-6 receptor), leading to the Food and Drug Administration (FDA) approval of specific treatments for AQP4-IgG+NMOSD for the first time. Most recently, ravulizumab (anti-C5 complement inhibitor) was also shown to be highly efficacious in an open-label, external-controlled trial...Observational studies showed that tocilizumab was associated with a decrease in relapses, whereas rituximab seemed to have less robust effectiveness in MOGAD compared to AQP4-IgG+NMOSD. Herein, we review the evidence on the efficacy and safety of each monoclonal antibody therapy used in AQP4-IgG+NMOSD and MOGAD, including special considerations in children and women of childbearing potential.

P2/3, N=422, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

P3, N=344, Recruiting, Ascentage Pharma Group Inc. | Not yet recruiting --> Recruiting

The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). An increase of <50% in acMMAE/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit-risk profile support the use of polatuzumab vedotin 1.8 mg/kg once every 3 weeks with R-CHP for six cycles in patients with previously untreated DLBCL.

P1, N=112, Recruiting, Guangzhou Lupeng Pharmaceutical Company LTD. | Not yet recruiting --> Recruiting

P1/2, N=66, Not yet recruiting, National Cancer Institute (NCI)

P2, N=260, Recruiting, Swiss Group for Clinical Cancer Research | Trial primary completion date: Mar 2026 --> Oct 2025

The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.

We performed bendamustine-rituximab (BR)-combined therapy. After six courses of BR-combined therapy, colonoscopy revealed improvement in the lead pipe sign and CT revealed disappearance of the mass.

P=N/A, N=89, Recruiting, AbbVie

P3, N=490, Not yet recruiting, InnoCare Pharma Inc.

P2, N=30, Not yet recruiting, Anhui Provincial Hospital

P3, N=850, Not yet recruiting, Celgene

P2, N=30, Recruiting, Columbia University | Trial completion date: Feb 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024

P2, N=92, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Mar 2028 | Trial primary completion date: Apr 2024 --> Mar 2028

P3, N=270, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2025 --> Mar 2025

Immunomodulatory drugs like lenalidomide reduce the levels of MCL-associated CD163+ macrophages and enhance macrophage phagocytic activity. Similarly, clinical approaches targeting the CD47 "don't eat me" signalling, in combination with the anti-CD20-antibody rituximab, demonstrate increased macrophage activity and phagocytosis of MCL tumour cells. Cell-based therapies such as chimeric antigen receptor (CAR) T-cell have shown promise but various challenges persist, leading to a potential interest in CAR-macrophages (CAR-M). When macrophages are recruited to the TME, they offer advantages including phagocytic function and responsiveness to microenvironment alterations, suggesting their potential as a manipulable and inducible alternative when CAR T-cell therapies fails in the complex landscape of MCL treatment.

Heterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

P3, N=230, Recruiting, Kite, A Gilead Company | Trial completion date: Jan 2031 --> Oct 2030 | Trial primary completion date: Jan 2031 --> Oct 2030

P3, N=250, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

P1/2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Dec 2026 --> Dec 2028

P1/2, N=83, Active, not recruiting, National Cancer Institute (NCI)

P3, N=0, Withdrawn, Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | N=200 --> 0 | Not yet recruiting --> Withdrawn

P2, N=80, Recruiting, Mayo Clinic | N=55 --> 80

Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142).

P1, N=66, Completed, BeiGene | Recruiting --> Completed

P3, N=120, Not yet recruiting, Centre Hospitalier Universitaire de Nice