ALLO-501 CAR T Cells for Lymphoma

(ALPHA Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALLO-501 for individuals with certain types of lymphoma, specifically large B-cell lymphoma or follicular lymphoma, who have not succeeded with at least two rounds of chemotherapy. The main goal is to determine if ALLO-501 is safe and effective for these patients. Eligible participants must have a confirmed diagnosis of these lymphomas and a measurable tumor but must not have recently received certain other treatments, such as stem cell transplants or specific types of gene therapy. As a Phase 1 trial, this research focuses on understanding how ALLO-501 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ALLO-501 CAR T cells have a manageable safety profile in patients with large B-cell lymphoma who have not previously received CD19 CAR T-cell therapy. The side effects were generally expected and controllable. Studies have not identified any unusual side effects compared to similar treatments, suggesting that ALLO-501 is well-tolerated. Although the treatment remains under investigation, early results indicate promising safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ALLO-501 CAR T cells for lymphoma because it represents a new frontier in cancer treatment. Unlike traditional chemotherapy or radiation, which attacks cancer cells broadly, ALLO-501 specifically targets cancerous B cells, potentially reducing collateral damage to healthy tissue. This treatment uses allogeneic CAR T cells, meaning they are derived from healthy donors rather than being custom-made for each patient, which could make the treatment more accessible and quicker to administer. Additionally, combining ALLO-501 with ALLO-647 may help to better manage the body's immune response, enhancing the effectiveness and safety of the therapy.

What evidence suggests that ALLO-501 could be an effective treatment for lymphoma?

Research has shown that ALLO-501 CAR T cells hold promise for treating large B-cell lymphoma and follicular lymphoma. In this trial, participants will receive ALLO-501. Specifically, studies found that patients who received ALLO-501 experienced significant and lasting improvements, with an average response duration of 23.1 months. Among patients observed for six months, 62.5% achieved complete remission, meaning no cancer was detected, and 50% remained in complete remission for the entire six months. This suggests that ALLO-501 could be an effective option for those whose lymphoma has returned or not responded to other treatments. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01933

Allogeneic Chimeric Antigen Receptor T-Cell Products ... B cells were detectable starting 4 months after treatment in responders, whereas T-cell counts recovered to baseline between 6 and 9 months ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39946666/

Allogeneic Chimeric Antigen Receptor T-Cell ... - PubMed - NIH Conclusion: Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve ...

3. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-presents-positive-phase-1-data-allo-501

Press Release Data presented from the ALPHA trial supports the ability of a single administration of ALLO-501 to generate deep and durable responses at a rate that is ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03939026

Safety and Efficacy of ALLO-501 Anti-CD19 Allogeneic ... 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- ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT421132

Phase 1 results with anti-CD19 allogeneic CAR T ALLO- ... Median DOR was 23.1 months. Among 8 pts with the opportunity to be followed for 6 months, 5 (62.5%) had achieved CR and 4 (50.0%) sustained CR through 6 months.

6. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-presents-comprehensive-safety-data

Press Release The addition of ALLO-647 to standard lymphodepletion did not result in adverse events beyond those commonly observed with autologous CAR T cell ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04416984

NCT04416984 | Safety and Efficacy of ALLO-501A Anti- ... The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma.