CAR T Cell Therapy for Large B-Cell Lymphoma

(ALPHA2 Trial)

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

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. 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 and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

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.

What safety data is available for CAR T Cell Therapy in treating large B-cell lymphoma?

CAR T Cell Therapy, specifically targeting CD19, has been evaluated for safety in various studies. The therapy is associated with some adverse events, including cytokine release syndrome (33-69%), neurotoxicity (8-33%), and B-cell aplasia (54%). However, the therapy has shown a good safety profile in some trials, with no serious adverse events directly attributed to the treatment and no dose-limiting toxicities reported. The risk of graft-versus-host disease is low, especially with off-the-shelf CAR T-cell therapies. Infectious complications are a concern, and optimal antimicrobial prophylaxis strategies are still being studied. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy, including treatments like ALLO-501A, has been studied for safety in various conditions like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Common side effects include cytokine release syndrome (a reaction causing fever and low blood pressure) and neurotoxicity (nerve damage), but serious adverse events are rare. Overall, it is considered safe with manageable side effects. ^{1 2 3 4 5}

Is the treatment ALLO-501A a promising treatment for large B-cell lymphoma?

Yes, ALLO-501A, a type of CAR T-cell therapy, is a promising treatment for large B-cell lymphoma. It uses specially modified immune cells to target and fight cancer cells, offering new hope for patients who have not responded to other treatments. ^{6 7 8 9 10}

How is the treatment ALLO-501A different from other treatments for large B-cell lymphoma?

ALLO-501A is a type of CAR T-cell therapy that uses specially modified immune cells to target and destroy cancer cells, specifically those with the CD19 marker. Unlike traditional treatments, it involves using donor-derived (allogeneic) T-cells, which can be more readily available than the patient's own cells, potentially offering a quicker treatment option. ^{6 7 8 9 10}

What data supports the idea that CAR T Cell Therapy for Large B-Cell Lymphoma is an effective treatment?

The available research shows that CAR T Cell Therapy is an effective treatment for Large B-Cell Lymphoma. In a study comparing CAR T Cell Therapy to another treatment called alloHCT, patients who received CAR T Cell Therapy had a longer median survival time of 475 days compared to 285 days for those who received alloHCT. Additionally, after receiving the treatment, 68% of CAR T Cell patients were still alive after 12 months, compared to 54% of alloHCT patients. This suggests that CAR T Cell Therapy may be a better option for patients with this type of lymphoma. ^{8 11 12 13 14}

What data supports the effectiveness of the treatment ALLO-501A for large B-cell lymphoma?

Research shows that CD19-directed CAR T-cell therapy, like ALLO-501A, is a standard treatment for relapsed or refractory large B-cell lymphoma, with outcomes not inferior to other treatments like allogeneic transplantation. Patients receiving CAR T-cell therapy had a median overall survival of 475 days, suggesting it is a viable option for this condition. ^{8 11 12 13 14}

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

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 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]

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]

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]

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]

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]

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 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 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]

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]

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]

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. United States 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. [2021]

2. England 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. [2021]

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

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. [2022]

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

Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. [2022]

5. United States 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. [2020]

6. 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]

7. 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]

8. England 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. [2022]

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

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

10. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

11. 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]

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

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. [2020]

14. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]