CAR T Cell Therapy for Large B-Cell Lymphoma

(ALPHA2 Trial)

Not currently recruiting at 26 trial locations

Overseen By Allogene Therapeutics Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Allogene Therapeutics

Disqualifiers: CNS involvement, Thyroid disorder, Active malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

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-501A, a type of CAR T cell therapy, for individuals with certain blood cancers, specifically large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The trial aims to assess the safety and effectiveness of this treatment for those whose cancer has not responded to or has returned after other treatments. Suitable candidates include individuals with these cancers who have undergone at least two other treatments and still have a measurable tumor. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had systemic anti-cancer therapy within 2 weeks before receiving ALLO-647.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anti-cancer therapy at least 2 weeks before receiving ALLO-647. The protocol does not specify about other medications, so it's best to discuss with the trial team.

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

A previous study found that patients who received a one-time dose of ALLO-501A, a type of CAR T cell therapy, experienced lasting benefits. The positive effects of the treatment continued for a significant period. Administered after a specific preparation treatment, the therapy demonstrated a manageable safety profile, indicating that while side effects occurred, they were not too severe or difficult to manage.

Research has also shown that the treatment is generally well-tolerated, meaning most people did not experience major problems. It is important to note that this evidence comes from early studies, which often focus on ensuring the safety of treatments for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ALLO-501A for treating large B-cell lymphoma because it uses a unique approach called CAR T cell therapy. Unlike standard chemotherapy or immunotherapy, which can be harsh on the body, CAR T cell therapy involves engineering the patient's own immune cells to better recognize and attack cancer cells. ALLO-501A is an "off-the-shelf" product, meaning it doesn't require the lengthy process of customizing cells for each patient, potentially making it more accessible and faster to administer. This innovation could lead to more efficient treatments with fewer side effects compared to current options.

What evidence suggests that ALLO-501A might be an effective treatment for large B-cell lymphoma?

Research has shown that ALLO-501A, a type of cell therapy, holds promise for treating large B-cell lymphoma (LBCL) that has recurred or is difficult to treat. Studies have found that a single dose can have long-lasting effects. Currently, about 50% to 60% of LBCL patients do not fully respond to existing treatments. However, ALLO-501A, which participants in this trial may receive, could improve these outcomes. This therapy targets and attacks cancer cells more effectively. Early data suggests it is generally safe, offering hope for patients with challenging LBCL cases. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

Adults with relapsed or refractory large B-cell lymphoma who have tried at least two chemotherapy treatments can join. They should be relatively healthy (ECOG status 0 or 1), not have had certain recent treatments like radiation, and must not have active infections or other cancers treated in the last three years.

Inclusion Criteria

I am fully active or can carry out light work.

My condition did not improve after 2 different chemotherapy treatments.

My blood, kidney, and liver tests are within normal ranges.

Exclusion Criteria

I haven't had any cancer treatments in the last 2 weeks.

I have a thyroid disorder, but it's controlled with stable hormone therapy.

I had a stem cell transplant using my own cells within the last 6 months.

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-501A, an anti-CD19 allogeneic CAR T cell therapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• ALLO-501A
• Cyclophosphamide
• Fludarabine

Trial Overview The ALPHA-2 study is testing ALLO-501A CAR T cells after a prep treatment with fludarabine, cyclophosphamide, and ALLO-647. The goal is to see if this new therapy is safe and effective for patients whose lymphoma has come back or hasn't responded to previous treatments.

How Is the Trial Designed?

Group I: ALLO-501A, ALLO-647 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

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 significant promise in treating relapsed or refractory B-cell malignancies, such as B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia, by targeting specific antigens like CD19 and BCMA.

The review highlights both the efficacy and toxicity of CD19- and BCMA-targeted CAR-T-cell therapies, indicating that while these treatments can be effective, they also come with potential side effects that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. Roex, G., Feys, T., Beguin, Y., et al.[2020]

In a study comparing CD19-directed CAR T-cell treatment and allogeneic hematopoietic cell transplantation (alloHCT) for patients with multiply relapsed/refractory large B-cell lymphoma, CAR T-cell therapy showed a median overall survival of 475 days compared to 285 days for alloHCT, indicating a potential advantage in survival outcomes.

CAR T-cell treatment had significantly lower nonrelapse mortality (3% vs 21%) compared to alloHCT, suggesting it may be a safer option for patients, while overall outcomes were not inferior, supporting the use of CAR T cells as a preferred first-line cellular immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells or allogeneic transplantation as standard of care for advanced large B-cell lymphoma: an intent-to-treat comparison. Dreger, P., Dietrich, S., Schubert, ML., et al.[2021]

In a phase I trial involving 50 children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), 62% achieved complete remission after treatment with CD19-CAR T cells, especially benefiting from fludarabine/cyclophosphamide-based lymphodepletion.

Patients who achieved minimal residual disease-negative complete remission and subsequently underwent allogeneic hematopoietic stem-cell transplant (alloHSCT) had a significantly improved median overall survival of 70.2 months, indicating that this sequential treatment approach can lead to durable disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. Shah, NN., Lee, DW., Yates, B., et al.[2022]

In a study of 129 adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) treated with CD19-directed CAR T therapy, 95.4% were hospitalized during treatment, with a median hospital stay of 17 days, highlighting the intensive care required during this therapy.

The estimated 6-month risk of requiring subsequent treatment after CAR T was 36.2%, indicating a significant chance of treatment failure, and emphasizing the need for effective salvage therapies for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. Jalbert, JJ., Wu, N., Chen, CI., 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]

CD19-CAR T cell therapy is feasible and safe for treating children and young adults with refractory B-cell malignancies, with a maximum tolerated dose established at 1×10^6 CAR T cells per kg.

The treatment showed potent anti-leukaemic activity, with all toxicities being fully reversible, including severe cases of cytokine release syndrome in 14% of patients, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lee, DW., Kochenderfer, JN., Stetler-Stevenson, M., et al.[2022]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

In a study of 35 patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic stem cell transplantation, 85.7% achieved complete remission after receiving CD19-targeted CAR T cell therapy, indicating high initial efficacy.

However, the long-term outcomes were concerning, with a recurrence rate of 68.3% at 18 months and an overall survival rate of only 30.0%, suggesting that additional treatments may be necessary to improve long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Chen, YH., Zhang, X., Cheng, YF., et al.[2021]

Anti-CD19 CAR-T therapy has been approved for patients with relapsed/refractory diffuse large B cell lymphoma, showing promising clinical outcomes based on recent trials like ZUMA-1, JULIET, and TRANSCEND NHL-001.

Healthcare providers need to understand the indications, potential toxicities, and limitations of this therapy to effectively manage patient referrals and treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma. Havard, R., Stephens, DM.[2020]

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]

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 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]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2517

Phase 1 results with anti-CD19 allogeneic CAR T ALLO- ... A one-time dose of allogeneic CAR T therapy following LD with FCA90 provided durable responses with a manageable safety profile in patients with r/r/ LBCL.

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430976/

DURABLES RESPONSES ACHIEVED WITH ANTI-CD19 ... Background: Despite recent progress in treating LBCL, approximately 50% to 60% of pts will either not achieve a complete response (CR) or will ...

4. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-presents-updated-allo-501501a-phase-1-data

Allogene Therapeutics Presents Updated ALLO-501/501A ... Long-term follow up data from Phase 1 ALPHA/ALPHA2 trials demonstrate potential of allogeneic CD19 CAR T to generate durable complete responses similar to ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT332861

First-in-human data of ALLO-501A, an allogeneic chimeric ... First-in-human data of ALLO-501A, an allogeneic chimeric antigen receptor (CAR) T-cell therapy and ALLO-647 in relapsed/refractory large B-cell lymphoma (R/R ...

6. 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.