CAR T-Cells for Blood Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Systemic corticosteroids, Immunosuppressive therapy

Disqualifiers: Solid organ transplant, Active infection, CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 1 day

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for certain blood cancers that have returned or do not respond to existing treatments. The focus is on using specially modified immune cells, called BAFFR-based CAR T-cells (Chimeric Antigen Receptor T-cells), designed to locate and attack cancer cells. The trial aims to determine the safety of this approach and identify the best dose when combined with chemotherapy drugs. Individuals with specific blood cancers, such as chronic lymphocytic leukemia, follicular lymphoma, or large B-cell lymphoma, which have not responded to at least two previous therapies, may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a 100-day washout period required for those who have had prior CD19 directed CAR-T cell therapy.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that a new treatment using specially modified cells, called BAFFR-based CAR T-cells, is being developed to target certain blood cancers. In studies, these modified cells have specifically attacked and destroyed B-cell cancers, such as mantle cell lymphoma. Patients who received this treatment experienced some side effects common with this type of therapy, including fever, tiredness, and low blood cell counts. Although serious side effects, like a strong immune response called cytokine release syndrome, can occur, many patients handle the treatment well.

As a Phase 1 trial, this is an early stage of testing. The main goal is to ensure the treatment's safety and determine the best dose. While early results are promising in targeting cancer cells, more safety information is still being collected. Those considering participation should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BAFFR-based Chimeric Antigen Receptor (CAR) T-cells for blood cancer because these cells offer a new and targeted approach to treatment. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, CAR T-cells are engineered to specifically recognize and destroy cancer cells by targeting the BAFFR protein found on their surface. This precision reduces damage to healthy cells and potentially leads to fewer side effects. Additionally, CAR T-cell therapy has shown promise in providing long-lasting remission, which is a significant advancement over conventional treatments.

What evidence suggests that BAFFR-based CAR T-cells might be an effective treatment for blood cancer?

Research has shown that a new treatment using specially engineered cells, called BAFFR-based CAR T-cells, may effectively treat B-cell cancers. These cells are designed to specifically attack cancer cells. Participants in this trial will receive BAFFR-based CAR T-cells, which studies have found can successfully target and destroy various types of B-cell cancers. This method addresses the problem of cancer recurrence due to cancer cells changing to evade treatment. Early results suggest that these CAR T-cells can overcome this issue and effectively eliminate cancer cells. While more research is needed, initial evidence supports their potential effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Mohamed Kharfan-Dabaja, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with various B-cell blood cancers that have either returned after treatment or haven't responded to previous treatments. Participants must meet specific health criteria not detailed here.

Inclusion Criteria

Measurable disease

Hematologic parameters within specified ranges

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I had a stem cell transplant using my own cells less than 60 days ago.

I have had a stem cell transplant from a donor.

I have had a solid organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis

Patients undergo leukapheresis to collect T cells for modification

1 day

1 visit (in-person)

Lymphodepletion

Patients receive cyclophosphamide and fludarabine or bendamustine to prepare the body for CAR T-cell infusion

3-5 days

3-5 visits (in-person)

Treatment

Patients receive BAFFR-based chimeric antigen receptor T-cells infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Multiple visits (in-person and virtual) at specified intervals

What Are the Treatments Tested in This Trial?

Interventions

• BAFFR-based Chimeric Antigen Receptor T-cells
• Cyclophosphamide
• Fludarabine

Trial Overview The trial is testing a new therapy where patient's T-cells are modified in the lab to attack cancer cells, combined with chemotherapy drugs fludarabine and cyclophosphamide to prepare the body for these engineered T-cells.

How Is the Trial Designed?

Group I: Treatment (BARRF based chimeric antigen receptor T-cells) Experimental Treatment 12 Interventions

Patients undergo leukapheresis. Patients then receive cyclophosphamide IV, over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and MRI at screening, CT scan, PET scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells show promise in treating blood cancers, particularly with CD19-CAR-T cells demonstrating strong clinical responses in B-cell malignancies.

To enhance the effectiveness and safety of these therapies, researchers are exploring new antigens, improved T cell culture methods, and better administration protocols to address issues like treatment failure and toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming key challenges in cancer immunotherapy with engineered T cells. Arcangeli, S., Mestermann, K., Weber, J., et al.[2021]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

A total of 3225 adverse event reports were analyzed for two chimeric antigen receptor T-cell therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel), revealing that cytokine release syndrome (52.2%) and neurotoxicity (27.2%) were the most common toxicities, often occurring within the first 10 days after treatment.

The study identified specific emerging safety signals, such as a higher risk of cardiomyopathies and gastrointestinal perforations associated with axi-cel, and hepatotoxicity and pupil disorders linked to tisa-cel, highlighting the need for ongoing monitoring of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database. Fusaroli, M., Isgrò, V., Cutroneo, PM., et al.[2022]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

The novel BAFF-R CAR T-cell therapy shows promise in treating B-cell malignancies, particularly in cases where traditional CD19-targeted therapies may fail due to antigen loss, with effective elimination of BAFF-R expressing tumors demonstrated in mouse models.

This therapy has been developed under strict manufacturing standards and has passed necessary FDA testing, paving the way for a Phase 1 clinical trial in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions. Dong, Z., Cheng, WA., Smith, DL., et al.[2020]

BAFF CAR-T cells, developed using a non-viral gene delivery method, effectively target and kill various B cell cancers, including mantle cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia, both in laboratory settings and in animal models.

These CAR-T cells bind to three different BAFF receptors, which helps reduce the risk of cancer cells escaping treatment by losing the targeted antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Wong, DP., Roy, NK., Zhang, K., et al.[2023]

CAR T cell therapy is an innovative treatment for patients with relapsed and refractory blood cancers, with two FDA-approved formulations now available and expanding into broader oncology practices.

However, about 50% of patients experience neurological toxicities from this treatment, which can lead to serious complications, highlighting the need for careful monitoring and management of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological Complications of CAR T Cell Therapy. Landry, K., Thomas, AA.[2021]

CAR T-cell therapy, particularly with agents like Tisagenlecleucel (Kymriah®) and axicabtagene ciloleucel (Yescarta®), has shown strong overall response and survival rates in treating B-cell malignancies, including pediatric acute lymphoblastic leukemia and adult diffuse large B-cell lymphoma.

These therapies utilize the patient's own modified T cells to target CD19, a common antigen in B-cell cancers, and the field is rapidly evolving with new agents and indications being developed for broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy: Update on the State of the Science. Lamprecht, M., Dansereau, C.[2020]

Chimeric antigen receptor (CAR) T-cell therapy has shown promising results in prolonging survival for patients with relapsed or refractory B-cell malignancies, as evidenced by numerous clinical trials targeting CD19 and CD20.

While CAR T-cell therapy is generally safe and well-tolerated, potential safety concerns include insertional mutagenesis, off-target effects, and inflammatory responses, which need to be carefully monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in immunotherapy of hematological malignancies by using chimeric antigen receptor-modified lymphocytes]. Xu, XJ., Zhao, HZ., Tang, YM.[2018]

The development of BAFF-R CAR T cells shows promise in treating B cell malignancies, effectively targeting tumors even when CD19 expression is lost, which is a common issue with current therapies.

In preclinical models, BAFF-R CAR T cells successfully eradicated established tumors and demonstrated antitumor activity against relapsed cases of acute lymphoblastic leukemia (ALL) that had lost CD19 expression, suggesting a potential solution to tumor relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Qin, H., Dong, Z., Wang, X., et al.[2020]

CAR T-cell therapy is an effective treatment for acute lymphocytic leukemia and B-cell lymphoma, but it requires at least 7 days of hospitalization to monitor for serious side effects like cytokine release syndrome and neurotoxicity.

Early identification and treatment of these toxicities by nursing staff can reverse potentially life-threatening complications, highlighting the importance of objective assessment and consensus grading in managing CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Emergencies: Inpatient Administration, Assessment, and Management. Jackson, S., Wheatley, T.[2021]

Adoptive cell therapy using CAR-modified T cells has shown promising results, achieving complete remission in patients with B cell malignancies over the long term.

There are currently around 100 ongoing clinical trials exploring CAR T cell therapies for various blood cancers and solid tumors, highlighting the rapid advancement and interest in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The growing world of CAR T cell trials: a systematic review. Holzinger, A., Barden, M., Abken, H.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06191887

B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric ... This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7015136/

CAR T cells targeting BAFF-R can overcome CD19 antigen ... CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924003732

Analysis of polyfunctionality for enhanced BAFF-R CAR T ... Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic strategy for eradicating human cancers.

4. nature.com nature.com/articles/s41467-021-27853-w

A BAFF ligand-based CAR-T cell targeting three receptors ... We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20558759

Safety and Efficacy of B-cell Activating Factor Receptor ... The purpose of this study is to assess the safety and tolerability of escalating doses of MC10029 following lymphodepleting (LD) therapy in subjects with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8752722/

A BAFF ligand-based CAR-T cell targeting three receptors ... We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell ...

7. mayoclinic.org mayoclinic.org/departments-centers/car-t-cell-therapy-program/sections/clinical-trials/rsc-20405550

CAR-T Cell Therapy Program - Clinical trials The purposes of this study are to explore the therapeutic efficacy of BAFFR-CAR T cells in BAFFR-expressing B-cell hematologic malignancies ...