BAFF CAR-T for Non-Hodgkin Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Paolo F. Caimi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Luminary Therapeutics

Must not be taking: Immunosuppressants, others

Disqualifiers: CNS involvement, Active infection, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new immune cell therapy for patients with non-Hodgkin lymphoma who haven't responded to other treatments. The therapy involves modifying the patient's own immune cells to better recognize and attack their cancer.

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.

What data supports the effectiveness of the treatment BAFF CAR-T for Non-Hodgkin Lymphoma?

CAR-T cell therapy, which is similar to BAFF CAR-T, has shown success in treating other types of lymphoma, like large B-cell lymphoma, with long-lasting remissions in nearly half of the patients. This suggests that BAFF CAR-T might also be effective for Non-Hodgkin Lymphoma. ^{1 2 3 4 5}

What safety data exists for BAFF CAR-T therapy in humans?

CAR-T cell therapy, including BAFF CAR-T, can have serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Researchers are working on strategies to reduce these risks, such as modifying the CAR-T cells to make them safer. While these therapies have shown promise in treating certain cancers, they can sometimes lead to life-threatening complications, so safety measures are crucial. ^{6 7 8 9 10}

What makes BAFF CAR-T treatment unique for non-Hodgkin lymphoma?

BAFF CAR-T treatment is unique because it involves engineering a patient's own T-cells to specifically target and attack cancer cells, which is different from traditional chemotherapy that affects both cancerous and healthy cells. This approach is part of a new wave of therapies that offer hope for patients with relapsed or refractory non-Hodgkin lymphoma, who have limited options with conventional treatments. ^{1 11 12 13 14}

Research Team

Paolo F. Caimi, MD

Principal Investigator

Cleveland Clinic Taussig Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• BAFF CAR-T (CAR T-cell Therapy)

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.

Participant Groups

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+

Dr. Gary K. Schwartz

Case Comprehensive Cancer Center

Chief Executive Officer since 2023

MD, FASCO

Dr. Nathan Berger

Case Comprehensive Cancer Center

Chief Medical Officer since 2020

MD

Findings from Research

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]

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]

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]

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]

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]

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-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 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]

References

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

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. [2023]

2. United States 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. [2023]

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

Clinical Perspective: Treatment of Aggressive B Cell Lymphomas with FDA-Approved CAR-T Cell Therapies. [2022]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Bispecific CAR T-cells for B-cell Malignancies. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. [2023]

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

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. [2021]

9. Netherlands 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. [2023]

12. Japan pubmed.ncbi.nlm.nih.gov

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

13. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

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

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. [2021]