CAR-T Therapy for T-Cell Lymphoma

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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a Phase 1, first-in-human (FIH), open-label, multicenter, study of LB1901 administered to adult subjects with histologically confirmed CD4+ relapsed or refractory Peripheral T-cell lymphoma (PTCL) (PTCL not otherwise specified \[PTCL-NOS\] and angioimmunoblastic \[AITL\]), or relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Sézary syndrome \[SS\] and mycosis fungoides \[MF\]).

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 CAR-T therapy generally safe for humans?

CAR-T therapy has shown a manageable safety profile in various studies, with common side effects including 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 generally manageable with proper medical care, and no severe adverse events were directly attributed to the treatment in some trials. ^{1 2 3 4 5}

How is the treatment LB1901 for T-Cell Lymphoma different from other treatments?

LB1901 is a CAR-T therapy, which is a type of treatment that uses genetically modified T-cells to target and destroy cancer cells. This approach is unique because it specifically targets the T-cell receptor β-chain constant region 1, offering a new way to treat T-cell lymphomas, which currently have limited standard treatment options. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment LB1901 for T-Cell Lymphoma?

CAR-T therapy has shown success in treating other types of lymphomas, such as large B-cell lymphoma, with durable remissions in nearly half of the patients. This success has led to the expansion of CAR-T therapy to other lymphoma types, suggesting potential effectiveness for T-cell lymphoma as well. ^{6 7 11 12 13}

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

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]

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]

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]

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]

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]

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]

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]

Citations

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

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

2. England pubmed.ncbi.nlm.nih.gov

Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy. [2022]

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

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

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

CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. [2022]

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

Constant attack on T cell lymphomas. [2018]

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

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. [2023]

9. United States 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. [2022]

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

GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]

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

Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. [2023]

13. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy in large B cell lymphoma. [2023]