CAR-T Therapy for T-Cell Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Legend Biotech

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Legend Biotech USA Inc

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: CD8+ TCL, Cellular immunotherapy, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LB1901, for specific types of T-cell lymphoma, such as Peripheral T-cell lymphoma (PTCL) and Cutaneous T-cell lymphoma (CTCL). LB1901 is a type of CAR-T therapy, a form of immunotherapy. The main goal is to determine the treatment's safety and its effects on cancer. It targets those whose cancer has not responded to at least two other treatments. Individuals with T-cell lymphoma, like Sézary syndrome or mycosis fungoides, who have not found success with other treatments, might be suitable candidates. As a Phase 1 trial, this research aims to understand 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 requires stopping certain medications before participating. You must stop any systemic anticancer therapy, immunosuppressants, therapeutic anticoagulants, and CNS disease prophylaxis within specific timeframes before apheresis (blood collection).

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

Research has shown that LB1901, a new CAR-T therapy, could be effective in treating T-cell lymphomas. In lab studies, LB1901 attacked cancer cells without harming healthy ones. However, some safety concerns exist. The FDA temporarily paused a trial of LB1901 to review safety information. This pause does not indicate the treatment is unsafe; it is a precaution to understand all possible risks.

As a Phase 1 trial, this is the first time the treatment is tested in humans. Phase 1 trials focus on safety, so detailed safety information is not yet available. Treatments in this stage are generally closely monitored for side effects. Trial participants will be carefully observed to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for T-cell lymphoma, which often include chemotherapy and radiation, LB1901 uses a cutting-edge approach called CAR-T cell therapy. CAR-T therapy works by genetically modifying a patient's own T cells to better recognize and attack cancer cells. In the case of LB1901, these T cells are engineered with a chimeric receptor targeting CD4, a protein often found on the surface of T-cell lymphoma cells. This targeted mechanism not only offers a personalized treatment option but also has the potential to be more effective with fewer side effects compared to traditional therapies. Researchers are particularly excited about LB1901 because it represents a novel way to harness the body's immune system to fight cancer more precisely.

What evidence suggests that LB1901 might be an effective treatment for T-cell lymphoma?

Research has shown that anti-CD4 CAR T cells, like those used in the treatment arm of this trial with LB1901, might offer a promising treatment for T-cell lymphomas that have returned or resisted other treatments. These specially designed cells target and destroy cancerous T-cells. Early results suggest that similar treatments have succeeded in other serious blood cancers. The main idea is that these modified T-cells can identify and attack lymphoma cells, potentially leading to better patient outcomes. While LB1901 remains under study in this trial, this approach builds on successful results from similar CAR T-cell therapies. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with CD4+ Peripheral T-cell lymphoma or Cutaneous T-cell lymphoma that's come back or hasn't responded to treatment. They must have tried at least two other cancer treatments, and if they've got a certain type of PTCL or mycosis fungoides, they need to have had brentuximab vedotin before. Participants should be fairly healthy (ECOG 0-1), not pregnant, willing to use birth control, and can't donate eggs or sperm for a year after the trial.

Inclusion Criteria

Written informed consent.

I have CD30+ PTCL or MF and have been treated with brentuximab vedotin.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken immunomodulatory drugs in the last 7 days.

I haven't taken any monoclonal antibody treatments in the last 4 weeks.

My cancer was fully treated or removed and has been in remission for over 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• LB1901

Trial Overview The study is testing LB1901, which is a new type of cell therapy called CAR-T specifically targeting CD4 cells in people with certain types of advanced T-cell lymphomas. It's an early-phase trial meant to see how safe it is and how well it works.

How Is the Trial Designed?

Group I: Experimental LB1901 Experimental Treatment 1 Intervention

Drug: anti-CD4 CAR T cells anti-CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells.

Who Is Running the Clinical Trial?

Legend Biotech USA Inc

Lead Sponsor

Trials

3

Recruited

150+

Published Research Related to This Trial

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

In a study of 182 patients with relapsed/refractory large B-cell lymphoma, novel CAR T-cell therapies showed varying efficacy and safety compared to the FDA-approved Yescarta, with some constructs like tandem CD19.CD20.4-1BBζ demonstrating favorable outcomes.

While some experimental CARs had improved safety profiles, they did not consistently outperform Yescarta in terms of progression-free survival, indicating that further research is needed to establish the best treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. Weinstein, B., Muresan, B., Solano, S., et al.[2022]

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]

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]

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]

A new CAR immunotherapy targeting CD4 has been developed using NK-92 cells, showing strong effectiveness in eliminating CD4+ T-cell leukemia and lymphoma cell lines, as well as patient samples in laboratory tests.

In animal models, CD4CAR NK-92 cells significantly improved survival by effectively targeting and destroying difficult-to-access lymphoma nodules, suggesting a promising new treatment strategy for aggressive peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Pinz, KG., Yakaboski, E., Jares, A., et al.[2023]

In the ZUMA-12 study involving 40 patients with high-risk large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high complete response rate of 78% and an overall response rate of 89%, indicating its effectiveness as a first-line treatment.

The safety profile of axi-cel was manageable, with only 8% of patients experiencing severe cytokine release syndrome and 23% experiencing neurological events, and no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Neelapu, SS., Dickinson, M., Munoz, J., et al.[2023]

The ZUMA-7 trial showed that axicabtagene ciloleucel (axi-cel) significantly improves overall survival and event-free survival compared to standard-of-care treatments for early-relapsed or refractory large B cell lymphoma, marking a major advancement in treatment options after nearly 30 years.

CAR T cell therapies, particularly axi-cel and lisocabtagene maraleucel (liso-cel), are proving effective as second-line treatments for elderly and transplant-ineligible patients, with potential for use as first-line therapies for high-risk large B cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving Role of CAR T Cell Therapy in First- and Second-Line Treatment of Large B Cell Lymphoma. Lionel, AC., Westin, J.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36172388/

Treatment of aggressive T-cell lymphoma/leukemia with ... CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are ...

2. onclive.com onclive.com/view/fda-places-clinical-hold-on-phase-1-trial-examining-car-t-cell-therapy-lb1901-in-t-cell-lymphoma

FDA Places Clinical Hold on Phase 1 Trial Examining CAR ... The FDA has placed a clinical hold on a phase 1 trial evaluating the safety and efficacy of the autologous CAR T-cell product LB1901 as a ...

3. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00044-2

An anti-CD19/CTLA-4 switch improves efficacy and ... CAR/CCR T cells demonstrate superior efficacy in xenograft mouse models compared with CAR T cells, superior long-term activity, and superior ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1465324925007200

The next innovations in chimeric antigen receptor T cell ... In a five-year follow-up study, CD19 targeted CAR T cell therapy for refractory B-cell lymphoma displayed an overall survival rate of 43%, with 64% of those ...

5. oncotarget.com oncotarget.com/article/5582/text/

Efficiency of CD19 chimeric antigen receptor-modified T ... This meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e14510

Preclinical analysis of an autologous CD4-targeted ... The in vitro and in vivo studies showed that LB1901 did not “mask” the CD4 antigen but exhibited potent anti-tumor activity without off-target effects.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7781235/

Safety and feasibility of anti-CD19 CAR T cells with fully ... Anti-CD19 chimeric antigen receptor (CAR)-expressing T cells are effective treatment for B-cell lymphoma but often cause neurologic toxicity.

8. astctjournal.org astctjournal.org/article/S2666-6367(23)01616-0/fulltext

Progress and Pitfalls of Chimeric Antigen Receptor T Cell ... An early description of conventionally manufactured CD5 CAR reported outcomes of 5 patients with R/R non-Hodgkin T cell lymphoma. CD5 CAR dosing ...