ALLO-501 CAR T Cells for Lymphoma

(ALPHA Trial)

Recruiting at 7 trial locations

Overseen By Allogene

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allogene Therapeutics

Must not be taking: Immunosuppressants

Disqualifiers: CNS lymphoma, Immunodeficiency, Thyroid disorder, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

74 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the ALPHA study is to assess the safety, efficacy, cell kinetics and immunogenicity of ALLO-501 in adults with relapsed or refractory large B-cell lymphoma or follicular lymphoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot be on systemic anticancer therapy within 2 weeks before joining the study or ongoing immunosuppressive agents.

What data supports the effectiveness of the treatment ALLO-501 CAR T Cells for Lymphoma?

Research shows that CAR T-cell therapy, like ALLO-501, has been effective in treating various types of lymphoma, including diffuse large B-cell lymphoma and mantle cell lymphoma, by targeting specific antigens on cancer cells. Additionally, combining CAR T-cell therapy with other treatments, such as immune checkpoint inhibitors, may enhance its effectiveness. ^{1 2 3 4 5}

What safety data exists for ALLO-501 CAR T Cells for Lymphoma?

ALLO-501 CAR T cells, targeting CD19, have been studied in various trials for B-cell malignancies, showing some common side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (damage to the nervous system), but these were generally manageable. In one study, no serious adverse events were directly attributed to the treatment, and no patients experienced neurotoxicity, indicating a favorable safety profile. ^{6 7 8 9 10}

What makes the ALLO-501 treatment unique for lymphoma?

ALLO-501 is a type of CAR-T cell therapy, which uses specially modified immune cells to target and destroy cancer cells in lymphoma. Unlike traditional treatments, it involves using allogeneic (donor-derived) cells, which can be more readily available and may reduce the time needed to start treatment. ^{1 2 11 12 13}

Eligibility Criteria

Adults with relapsed or refractory large B-cell lymphoma or follicular lymphoma can join this trial. They must have tried at least two chemotherapy treatments, have one measurable lesion, be in good physical condition (ECOG score of 0 or 1), and their major organs need to function well. People with CNS lymphoma, recent stem cell transplants, prior CD19 therapy, ongoing immunosuppressants, active GvHD, severe immunodeficiency disorders or uncontrolled thyroid disease cannot participate.

Inclusion Criteria

My blood, kidney, liver, lung, and heart functions are all within normal ranges.

At least 1 measurable lesion at time of screening

My condition did not improve after two chemotherapy treatments.

Exclusion Criteria

I have previously received treatments like CAR-T cell therapy.

Patients unwilling to participate in an extended safety monitoring period

I am currently taking medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647

1 week

Treatment

Participants receive ALLO-501, an anti-CD19 allogeneic CAR T cell therapy

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ALLO-501
• Cyclophosphamide
• Fludarabine

Trial Overview The ALPHA study is testing the safety and effectiveness of ALLO-501 Anti-CD19 Allogeneic CAR T Cells after a preparatory treatment with fludarabine, cyclophosphamide, and ALLO-647. The goal is to see how these cells work as a treatment for certain types of lymphoma that haven't responded to other therapies.

Participant Groups

Group I: ALLO-647, ALLO-501 Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Allogene Therapeutics

Lead Sponsor

Trials

7

Recruited

810+

Headquarters

South San Francisco, USA

Known For

Allogenic CAR T

Top Products

Cemacabtagene ansegedleucel (cema-cel), ALLO-501, ALLO-501A, ALLO-316

Findings from Research

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

CAR-T cell therapy has shown effectiveness in treating various types of blood cancers, including diffuse large B-cell lymphoma and mantle cell lymphoma, by targeting the CD19 antigen.

The study compares CAR-T cell therapy and allogeneic stem cell transplantation (ALLO-SCT) to determine the best scenarios for using each treatment, highlighting their shared immune mechanisms but differing characteristics in treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy. Castagna, L., Bono, R., Tringali, S., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy has shown effectiveness in treating B-cell leukemia and lymphoma, but there is a significant risk of relapse due to loss of targeted antigens or the CAR T-cells' intrinsic failures.

To improve long-term control of leukemia and lymphoma, researchers are exploring advanced strategies such as targeting multiple antigens simultaneously and combining CAR T-cell therapy with checkpoint inhibitors, which are currently in early clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials. Ormhøj, M., Abken, H., Hadrup, SR.[2022]

Allogeneic stem cell transplantation (allo-SCT) is a powerful treatment for hematologic malignancies, leveraging both intensive chemoradiotherapy and the immune response from donor cells to potentially cure diseases, though challenges like disease relapse and graft-versus-host disease remain significant.

The introduction of CAR-T cell therapy has transformed the treatment landscape for certain blood cancers, particularly acute lymphoblastic leukemia and specific lymphomas, indicating a shift in treatment paradigms and expanding options beyond traditional allo-SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms? Martino, M., Canale, FA., Naso, V., et al.[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]

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]

Allogeneic anti-CD19 CAR T-cell therapy shows high efficacy in treating relapsed or refractory acute lymphoblastic leukemia (ALL), with an 80% complete remission rate and a 51% one-year overall survival rate among patients.

The therapy demonstrates a favorable safety profile, with a low graft-versus-host disease (GvHD) rate of 4% and a manageable cytokine release syndrome rate of 69%, indicating it is a viable treatment option for both ALL and non-Hodgkin lymphoma (NHL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R/R ALL and NHL: A systematic review and meta-analysis. Chen, S., Zhang, Y., Fang, C., et al.[2022]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[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]

In a clinical trial involving 10 patients with B-cell malignancies that persisted after allogeneic hematopoietic stem cell transplantation, treatment with genetically modified T cells targeting the CD19 antigen led to tumor regressions in three patients, including one achieving complete remission.

The study demonstrated that these allogeneic anti-CD19-CAR T cells can effectively target and reduce B-cell malignancies without causing graft-versus-host disease (GVHD), a common complication in such treatments, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Kochenderfer, JN., Dudley, ME., Carpenter, RO., et al.[2023]

Cellular therapies, including CAR T cells and allogeneic stem cell transplantation, have shown significant effectiveness in treating aggressive non-Hodgkin lymphomas, particularly in patients with poor prognoses.

The article discusses the clinical approach to selecting patients for CD19-directed CAR T cell therapy, emphasizing its growing importance in lymphoma management and the potential of newer cell therapies to enhance immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cells. Chong, EA., Porter, DL.[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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials. [2022]

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

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms? [2023]

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

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

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R/R ALL and NHL: A systematic review and meta-analysis. [2022]

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

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. [2023]

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

Hematopoietic Stem Cell Transplantation in the Era of Engineered Cell Therapy. [2023]

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

Immunotherapy with cells. [2023]

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

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