AD-PluReceptor + Tafasitamab for Autoimmune Disorders

Recruiting in Palo Alto (17 mi)

Overseen by Chitra Hosing, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Rituximab, Voclosporin, Anifrolumab, others

Disqualifiers: Pulmonary disease, Cardiac manifestations, CNS pathology, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The goal of Safety Lead-In is to confirm the safety of tafasitamab when given to patients with SSc, SLE, and LN. The goal of Phase 1 is to find the recommended dose of AD-PluReceptor-NK cells in combination with tafasitamab and lymphodepleting chemotherapy that can be given to patients with the disease. The goal of Phase 2 is to learn if the dose of AD-PluReceptor-NK cells found in Phase 1 in combination with tafasitamab and lymphodepleting chemotherapy can help to control the disease.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that if you are on standard immunosuppressive therapy, it must have been started at least 12 weeks before screening and be stable for at least 8 weeks. Please consult with the trial team for specific guidance.

What data supports the effectiveness of the drug AD-PluReceptor + Tafasitamab for autoimmune disorders?

Research shows that targeting B cell-stimulating molecules like BAFF and APRIL, which are involved in autoimmune diseases, can be effective. Drugs like belimumab, which inhibit BAFF, have been approved for conditions like systemic lupus erythematosus, suggesting that similar approaches could be beneficial for other autoimmune disorders.

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How is the drug Tafasitamab-cxix different from other treatments for autoimmune disorders?

Tafasitamab-cxix is unique because it is a monoclonal antibody that targets CD19, a protein on the surface of B cells, which are involved in autoimmune responses. This is different from other treatments like rituximab, which targets CD20, another B cell protein, offering a novel approach to modulating the immune system in autoimmune disorders.

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Eligibility Criteria

This trial is for patients with autoimmune diseases like systemic sclerosis or scleroderma. Participants should have a diagnosis of these conditions and be suitable for the treatments being tested, which include chemotherapy.

Inclusion Criteria

I am fully active or can carry out light work.

I have been diagnosed with systemic sclerosis according to the 2013 criteria.

Positive ANA by immunofluorescence at titer ≥ 1:80

Exclusion Criteria

History of severe reactions to specified treatments

My condition does not meet any specific exclusion criteria for SLE.

I have severe heart problems due to lupus.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Confirm the safety of tafasitamab when given to patients with SSc, SLE, and LN

4-6 weeks

Phase 1

Determine the recommended dose of AD-PluReceptor-NK cells in combination with tafasitamab and lymphodepleting chemotherapy

8-12 weeks

Phase 2

Evaluate if the dose of AD-PluReceptor-NK cells found in Phase 1 can help control the disease

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Participant Groups

The study is testing AD-PluReceptor-NK cells combined with tafasitamab and lymphodepleting chemotherapy. It aims to confirm safety, find the best dose, and see if this combination can control autoimmune disorders effectively.

Group I: Safety Lead-In Experimental Treatment 1 Intervention

Group II: Dose Expansion Experimental Treatment 3 Interventions

Group III: Dose Escalation Experimental Treatment 3 Interventions

Tafasitamab-cxix is already approved in United States for the following indications:

🇺🇸 Approved in United States as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including those arising from low-grade lymphoma, in adult patients who are not eligible for autologous stem cell transplantation

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study. [2022] To assess the safety and biological activity of rozibafusp alfa, a first-in-class bispecific antibody-peptide conjugate targeting inducible costimulator ligand (ICOSL) and B cell activating factor (BAFF), in patients with rheumatoid arthritis (RA).

2. England pubmed.ncbi.nlm.nih.gov

Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. [2022] The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials. These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE. Post hoc analyses of these trials indicate that baseline serum levels of BAFF and BAFF/APRIL correlate with treatment response to belimumab and atacicept, respectively, suggesting a role for the two molecules as predictive biomarkers. It will, however, be important to refine future testing to identify active forms of BAFF and APRIL in the circulation, as well as to distinguish between homotrimer and heteromer configurations. In this review, we discuss the rationale for dual BAFF/APRIL inhibition versus single BAFF inhibition in autoimmune disease, by focusing on the similarities and differences between the physiological and pathogenic roles of the two molecules. A summary of the preclinical and clinical data currently available is also presented.

3. England pubmed.ncbi.nlm.nih.gov

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study. [2022] To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi.

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. [2020] Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).

5. United States pubmed.ncbi.nlm.nih.gov

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. [2019] To evaluate the safety, tolerability, and clinical effects of rituximab, an anti-CD20 monoclonal antibody, in the treatment of severe pediatric autoimmune diseases.

6. United States pubmed.ncbi.nlm.nih.gov

Drug insight: the mechanism of action of rituximab in autoimmune disease--the immune complex decoy hypothesis. [2015] Inflammatory responses to cell-associated or tissue-associated immune complexes are key elements in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and immune thrombocytopenic purpura. Effector cells, such as monocytes, macrophages and neutrophils, bind immune complexes in a process mediated by Fcgamma receptors, and these cells then initiate inflammatory reactions that lead to tissue destruction. Rituximab is an anti-CD20 monoclonal antibody that suppresses inflammation effectively in autoimmune diseases. It was initially approved by the FDA for the treatment of B-cell lymphomas and later for rheumatoid arthritis refractory to anti-tumor necrosis factor therapies. Rituximab is hypothesized to suppress disease injury in autoimmune diseases by promoting rapid and long-term elimination of circulating and possibly lymphoid-tissue-associated B cells. We suggest, however, that a different mechanism may underlie much of the therapeutic action of rituximab in autoimmune diseases: binding of tens of thousands of rituximab-IgG molecules to B cells generates decoy sacrificial cellular immune complexes that efficiently attract and bind Fcgamma receptor-expressing effector cells, which diminishes recruitment of these effector cells at sites of immune complex deposition and, therefore, reduces inflammation and tissue damage.

7. England pubmed.ncbi.nlm.nih.gov

Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). [2019] Rituximab, a chimeric monoclonal anti-CD20 antibody, has recently been used for the treatment of refractory antibody mediated autoimmune diseases such as immune mediated thrombocytopenia and haemolytic anaemia.