BAFF CAR-T for Non-Hodgkin Lymphoma

Recruiting at 1 trial location

Overseen By Paolo F. Caimi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Luminary Therapeutics

Must not be taking: Immunosuppressants, others

Disqualifiers: CNS involvement, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BAFF CAR-T, a type of cell therapy, for individuals with non-Hodgkin lymphoma. Researchers aim to determine if this treatment can benefit those whose cancer has not responded to other therapies, including CD19 CAR-T. Participants will receive varying doses to identify the safest and most effective one. Suitable candidates for this trial have non-Hodgkin lymphoma that has returned or not responded after at least two other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must wait more than 2 weeks since your last radiation or systemic therapy before participating, and at least 28 days must have passed since any investigational treatments.

Is there any evidence suggesting that BAFF CAR-T is likely to be safe for humans?

Research shows that BAFF CAR-T cells may help treat certain types of lymphoma, a kind of blood cancer. In an earlier study, three patients who received the smallest dose of BAFF CAR-T cells experienced only mild side effects, indicating that the treatment was generally well-tolerated at that dose.

As a phase 1 study, the main goal is to find the safest dose and gather early information on the treatment's effectiveness. Phase 1 trials primarily focus on safety, so researchers will closely monitor any serious side effects. Overall, the early results are promising for BAFF CAR-T cells as a potential new option for people with relapsed non-Hodgkin lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin Lymphoma, which often involve chemotherapy and monoclonal antibodies, BAFF CAR-T therapy offers a novel approach by using genetically modified T-cells. This treatment works by engineering the patient's own immune cells to specifically target and destroy cancer cells expressing the BAFF receptor. Researchers are excited about BAFF CAR-T because it represents a personalized therapy that could potentially lead to more precise targeting of cancer cells, reducing damage to healthy cells and possibly improving outcomes for patients who have not responded to conventional therapies.

What evidence suggests that BAFF CAR-T might be an effective treatment for non-Hodgkin lymphoma?

Research has shown that BAFF CAR-T cells, the investigational treatment in this trial, could be a promising option for relapsed non-Hodgkin lymphoma, especially when other treatments have failed. CAR-T cells involve modifying a patient's own immune cells to better combat cancer. Early results suggest that patients treated with BAFF CAR-T cells experienced few side effects. This treatment targets a different protein than the more common CD19 CAR-T cells, potentially benefiting patients who did not respond to those. Although still in early stages, this new approach offers hope for another option in challenging cases of non-Hodgkin lymphoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Paolo F. Caimi, MD

Principal Investigator

Cleveland Clinic Taussig Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with non-Hodgkin lymphoma that's come back after at least two treatments or hasn't responded to chemo can join. They need good liver, kidney, heart, and lung function, no brain lymphoma, and must use effective birth control. Those who've had recent other cancer treatments or have certain health issues like severe heart problems or active infections can't participate.

Inclusion Criteria

Serum creatinine < 1.5 mg/dL

My oxygen level is 92% or higher without extra oxygen.

My heart pumps well and I don't have fluid around it.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I have an active cancer other than non-dangerous skin cancer or early-stage cancers.

I have the most severe form of heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo a single lymphodepletion regimen prior to CAR-T cell infusion

1 week

Treatment

Participants receive BAFF CAR-T cell therapy with dose escalation to determine the maximum tolerated dose

24 months

Follow-up

Participants are monitored for safety, toxicity, and response to treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• BAFF CAR-T

Trial Overview The trial is testing a new therapy called BAFF CAR-T cells for people whose non-Hodgkin lymphoma didn't respond to previous treatments including CD19 targeted CAR-T cells. It aims to find the safest dose of BAFF CAR-T and see how well it works against the disease.

How Is the Trial Designed?

Group I: LMY-920 dose escalation Experimental Treatment 1 Intervention

Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.

Who Is Running the Clinical Trial?

Luminary Therapeutics

Lead Sponsor

Trials

3

Recruited

70+

Case Comprehensive Cancer Center

Collaborator

Trials

472

Recruited

33,400+

Published Research Related to This Trial

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

CAR-T cell therapies have been approved for treating patients with primary refractory or relapsed large B cell lymphoma (LBCL), providing new options for those who previously had limited treatments available.

The management of CAR-T cell therapies involves complex clinical decisions, including patient selection and follow-up care, highlighting the need for careful planning and monitoring in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Perspective: Treatment of Aggressive B Cell Lymphomas with FDA-Approved CAR-T Cell Therapies. Leick, MB., Maus, MV., Frigault, MJ.[2022]

In a study of 514 patients receiving CD19-directed CAR-T therapy for aggressive B-cell non-Hodgkin lymphoma, it was found that more lines of therapy before CAR-T and the use of bridging therapy were linked to worse progression-free survival (PFS) and overall survival (OS), with median PFS and OS of 7.6 and 25.6 months, respectively.

Allogeneic hematopoietic cell transplantation after CAR-T failure resulted in durable responses in over 50% of patients at one year, suggesting it may be a beneficial option for selected patients following CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL. Zurko, J., Nizamuddin, I., Epperla, N., et al.[2023]

CAR T-cell therapy targeting CD19 has significantly improved treatment outcomes for relapsed/refractory B-cell malignancies, but many patients still experience relapses due to antigen loss.

Bispecific CAR T-cells, such as those targeting CD19/CD20 and CD19/CD22, show promising efficacy and safety in early phase I trials, suggesting they may help reduce relapse rates, though further research in larger phase II studies is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CAR T-cells for B-cell Malignancies. Furqan, F., Shah, NN.[2022]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

CAR T cell therapy has shown great promise in treating certain blood cancers, but it can lead to serious side effects, including potentially fatal toxicities from cytokine release and off-target effects that harm healthy tissues.

Recent strategies to improve safety include modifying CAR structures and incorporating elements like switch molecules and suicide genes to reduce the toxic effects of CAR T cells on normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer. Sayadmanesh, A., Yekehfallah, V., Valizadeh, A., et al.[2023]

CAR-T cell therapy has shown great promise in treating hematological cancers, with two Anti-CD19 CAR-T therapies already approved for CD19-positive leukemia and lymphoma.

However, the therapy can cause serious side effects like cytokine release syndrome and on-target off-tumor toxicity, leading to some patients discontinuing treatment; researchers are exploring various safety strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Yu, S., Yi, M., Qin, S., et al.[2020]

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]

Lisocabtagene maraleucel (liso-cel), a CAR T-cell therapy targeting CD-19, achieved a 73% objective response rate and a 53% complete remission rate in patients with large B-cell lymphoma who had undergone a median of 3 prior therapies.

In the second-line treatment setting, liso-cel demonstrated superior event-free survival compared to standard care, highlighting its potential as a significant option for patients with relapsed or refractory large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. Mohty, R., Moreno Vanegas, Y., Chavez, JC., et al.[2023]

CAR T cell therapies have shown high response rates in treating relapsed and refractory large cell lymphomas, with some patients experiencing long-lasting benefits.

The review emphasizes the importance of patient selection and the need for strategies to prevent relapse, as well as ongoing research into new CAR T cell therapies and their mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. Perica, K., Palomba, L., Brentjens, RJ.[2021]

CD19-directed CAR-T therapy has shown promising long-term results, achieving durable remissions in nearly 50% of patients with relapsed/refractory large B-cell lymphoma, significantly improving their prognosis compared to the previous median survival of about 6 months with standard treatments.

The success of CAR-T therapy in large B-cell lymphoma has led to its expansion into other types of lymphomas, such as mantle cell and follicular lymphoma, and ongoing development of new CAR-T platforms aimed at enhancing efficacy and reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. Iqbal, M., Savani, BN., Hamadani, M.[2023]

Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising efficacy in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), with complete response rates of 40-60% in pivotal trials, and some patients achieving long-term remission.

While CAR-T therapy can lead to significant toxicities such as cytokine release syndrome and neurologic issues, these are generally treatable and reversible, making CAR-T a viable option for patients with poor prognosis in these lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR-T therapy for malignant lymphoma]. Shimoyama, T.[2023]

In a study of 25 patients with large B-cell lymphoma treated with CAR T-cell therapy, the objective response rates were 20% for tisagenlecleucel and 47% for axicabtagene-ciloleucel at 3 months, indicating variable efficacy based on the type of CAR T-cell used.

Bulky disease was identified as a significant negative predictor of response, with patients having bulky disease showing a median progression-free survival of only 2 months compared to 5 months for those without bulky disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study. Benoit, A., B Boies, MH., Déry, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06916767

Phase 1 Study of BAFF CAR-T Cells (LMY-920) for ... CAR-T cell treatment of refractory lymphoma has shown success, particularly with CD-19 targeted CAR-T cells, however, many participants are refractory or ...

2. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A282.info

244 A phase 1 study of novel transposon-based BAFF CAR ... Background CAR-T cells have demonstrated remarkable efficacy in non-Hodgkin Lymphoma (NHL). However, all currently approved CAR-T cell ...

3. cancernetwork.com cancernetwork.com/view/transposon-engineered-baff-car-t-cells-may-elicit-responses-in-lymphoma

Transposon-Engineered BAFF CAR-T Cells May Elicit ... Three patients treated at the first dose level of BAFF CAR-T cells experienced minimal adverse effects in a phase 1 study.

4. onclive.com onclive.com/view/dr-caimi-on-early-data-for-lmy-920-in-r-r-b-cell-nhl

Dr Caimi on Early Data for LMY-920 in R/R B-Cell NHL Paolo Caimi, MD, discusses the rationale behind evaluating LMY-920, a novel BAFF CAR T-cell therapy, in relapsed/refractory non-Hodgkin lymphoma.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S146532492500461X

EFFICIENT COST-EFFECTIVE MANUFACTURE OF A ... CD19 CART cell therapies have shown remarkable efficacy in non-Hodgkin lymphoma. However, durable response has been observed in less than half of treated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05312801

NCT05312801 | Phase 1 Study of BAFF CAR-T Cells (LMY ... This phase 1 study will evaluate safe dose and provide initial signal of the activity of BAFF CAR-T cells against relapsed non-Hodgkin lymphoma.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6534

PMB-CT01 (BAFFR-CAR T cell) therapy to examine ... BAFFR-CAR T cells are a promising therapeutic option for patients with r/r B-cell malignancies who are ineligible or failed prior CD19-targeted therapy.