T-Cell Therapy for Non-Hodgkin's Lymphoma

(STARLIGHT-1 Trial)

Overseen By Teresa Klask, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Estrella Biopharma, Inc.

Must be taking: Anti-CD20, Anthracyclines

Must not be taking: Systemic steroids, Calcineurin inhibitors

Disqualifiers: CNS pathology, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

21 Participants Needed

Trial Summary

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, if you are on certain treatments like systemic immunosuppressants or have had a recent live vaccine, you may need to discuss this with the trial team.

What data supports the effectiveness of the treatment EB103, CD19-Redirected ARTEMIS T-Cell Therapy for Non-Hodgkin's Lymphoma?

CD19-directed T-cell therapies, similar to EB103, have shown success in treating various B-cell cancers, including non-Hodgkin's lymphoma, with some patients experiencing long-term remission. These therapies have been recognized by the FDA for their potential, and they work by targeting specific markers on cancer cells, helping the immune system fight the disease more effectively. ^{1 2 3 4 5}

Is T-Cell Therapy for Non-Hodgkin's Lymphoma generally safe in humans?

T-Cell Therapy, specifically CD19 CAR T-cell therapy, has been tested in humans and generally shows a good safety profile, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a reaction where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (nerve damage). These side effects are usually manageable with proper medical care, although rare severe cases have been reported. ^{6 7 8 9 10}

How is the EB103 treatment different from other treatments for non-Hodgkin's lymphoma?

EB103, also known as CD19-Redirected ARTEMIS T-Cell Therapy, is unique because it uses modified T-cells to specifically target and attack cancer cells that express the CD19 protein, which is common in B-cell malignancies like non-Hodgkin's lymphoma. This approach is part of a broader category of treatments called CAR T-cell therapies, which have shown promise in achieving long-term remissions in some patients by redirecting the body's own immune cells to fight cancer. ^{1 3 4 11 12}

What is the purpose of this trial?

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of an autologous T-cell therapy (EB103) and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥ 18 years of age) who have relapsed/refractory (R/R) B-cell NHL. The study will include a dose escalation phase followed by an expansion phase.

Research Team

Pei Wang, PhD

Principal Investigator

Eureka Therapeutics Inc.

Eligibility Criteria

Adults over 18 with relapsed/refractory B-cell Non-Hodgkin's Lymphoma can join this trial. They should understand the risks and benefits, have good organ function, and an ECOG score of ≤2 (which means they are able to carry out daily activities). Prior treatments must be completed with stable side effects not worse than Grade 1.

Inclusion Criteria

I understand the study's risks and benefits and have signed the consent form.

My condition is relapsed or refractory B-cell non-Hodgkin's lymphoma.

My organs are functioning well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

A traditional dose escalation model (3+3 design) will be used to determine the Recommended Phase II Dose (RP2D)

21 months

Expansion

Additional subjects will be enrolled to further confirm the safety profile of EB103 at the RP2D and evaluate preliminary efficacy

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• EB103

Trial Overview The trial is testing EB103, a new T-cell therapy for those whose lymphoma has returned or didn't respond to treatment. It starts by finding the best dose and then checks how well it works in more people at that dose.

Participant Groups

Group I: EB103 Experimental Treatment 1 Intervention

Approximately six (6) subjects will be treated to determine the RP2D. At the designated RP2D, approximately fifteen (15) additional subjects will be treated.

Who Is Running the Clinical Trial?

Estrella Biopharma, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Eureka Therapeutics Inc.

Industry Sponsor

Trials

12

Recruited

160+

Findings from Research

CAR T cell therapy, which modifies T cells to target the CD19 antigen on B cells, has shown significant clinical effectiveness in treating various B cell malignancies, including chronic lymphocytic leukemia and acute lymphoblastic leukemia, with some patients experiencing long-term remissions.

The FDA has recognized the potential of CD19-directed CAR T cells by granting 'breakthrough' designation for their use in treating relapsed or refractory acute lymphoblastic leukemia in both adults and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies. Miller, BC., Maus, MV.[2023]

Chimeric antigen receptor (CAR) T-cell therapies have shown promising results in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma, offering complete and lasting clinical responses where traditional therapies have failed.

Four CD19-directed CAR T-cell therapies have been approved by the FDA for specific types of relapsed or refractory lymphomas, indicating a significant advancement in treatment options for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage? Kanwal, B.[2021]

The addition of the anti-CD20 monoclonal antibody rituximab to standard therapies has significantly improved overall survival rates in newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Innovative T-cell redirecting therapies, such as bispecific antibodies targeting both T-cell and B-cell antigens, have shown impressive efficacy in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma, leading to ongoing clinical trials exploring their combinations with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. Russler-Germain, DA., Ghobadi, A.[2023]

CD19CAR T cells have shown promising results in treating aggressive B-lineage cancers, but their effectiveness can be limited by the loss of the targeted CD19 antigen, leading to treatment failure.

The newly developed adapter CAR T cell technology (AdCAR) allows for multitargeting of different antigens, such as CD20 and CD22, which can enhance the anti-cancer activity and potentially overcome issues related to antigen loss in lymphoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

CTL019, an anti-CD19 chimeric antigen receptor T-cell therapy, received 'breakthrough therapy' designation from the FDA, marking it as the first personalized cellular therapy for cancer, with over 100 patients treated in clinical trials.

This therapy shows promise for patients with high-risk B-cell malignancies and is part of a growing field, with nearly 30 ongoing clinical trials targeting CD19 and efforts to expand CAR T-cell therapy to other types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Gill, S., June, CH.[2021]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

A case study highlights a rare but severe instance of neurotoxicity occurring 9 months after treatment with CD19-directed CAR T cells in a patient with relapsed large B-cell lymphoma, despite prior successful treatment and immunosuppression.

The presence of high CAR T-cell DNA levels and elevated inflammatory markers in the cerebrospinal fluid suggests that CAR T cells may infiltrate the brain and contribute to delayed neurotoxic effects, emphasizing the need for ongoing monitoring of neurological side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma. Jung, S., Greiner, J., von Harsdorf, S., et al.[2022]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

CAR T-cell therapy has shown promising results in early clinical trials for classic Hodgkin lymphoma (cHL), particularly with Epstein-Barr virus-specific T cells and CD30 CAR T cells, indicating potential for effective treatment options.

Research is ongoing into targeting the immunosuppressive tumor microenvironment in cHL using CD19 and CD123 CAR T cells, highlighting innovative strategies to enhance the efficacy of adoptive immunotherapy for this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy for Hodgkin lymphoma. Ho, C., Ruella, M., Levine, BL., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies. [2023]

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

Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage? [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]

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

Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. [2021]

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

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]

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

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). [2020]

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

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]

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

Adoptive T-cell therapy for Hodgkin lymphoma. [2022]