ALLO-647 + CAR T Cell Therapy for Large B-Cell Lymphoma

(EXPAND Trial)

Recruiting at 10 trial locations

Overseen By Allogene Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Allogene Therapeutics

Disqualifiers: CNS malignancy, Recent HSCT, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the EXPAND study is to assess the safety and clinical efficacy of ALLO-647 combined with fludarabine and cyclophosphamide compared to fludarabine and cyclophosphamide alone in a lymphodepletion regimen prior to ALLO-501A CAR T therapy in adults with relapsed or refractory large B-cell lymphoma

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment ALLO-647 + CAR T Cell Therapy for Large B-Cell Lymphoma?

Research shows that CD19-directed CAR T-cell therapy, which is part of this treatment, is effective for patients with relapsed or refractory large B-cell lymphoma, offering better survival outcomes compared to other treatments like allogeneic transplantation. Additionally, studies indicate that CAR T-cell therapy has been successful in treating similar conditions, such as diffuse large B-cell lymphoma, with a high response rate. ^{1 2 3 4 5}

What is the safety profile of ALLO-647 + CAR T Cell Therapy for Large B-Cell Lymphoma?

CAR T-cell therapies targeting CD19, like ALLO-647, have shown some common side effects, including cytokine release syndrome (a condition where the immune system becomes overly active) and neurotoxicity (nerve damage), but these are generally manageable with proper medical care. In some studies, these therapies have been used safely in patients with B-cell malignancies, with no serious adverse events directly attributed to the treatment. ^{6 7 8 9 10}

What makes ALLO-647 + CAR T Cell Therapy unique for treating large B-cell lymphoma?

ALLO-647 + CAR T Cell Therapy is unique because it uses allogeneic (donor-derived) CAR T cells, which are engineered to target CD19 on cancer cells, offering a potential treatment for patients who have not responded to other therapies. This approach differs from traditional autologous CAR T cell therapies, which use the patient's own cells, and may provide a more readily available treatment option. ^{1 3 11 12 13}

Eligibility Criteria

This trial is for adults with large B-cell lymphoma that has come back or hasn't responded to treatment. Participants must have had at least two prior chemotherapy treatments, be in good physical condition (ECOG status 0 or 1), and not have immune reactions against donor cells. They can't join if they've had a bone marrow transplant in the last six months or cancer affecting their central nervous system.

Inclusion Criteria

My condition did not improve after 2 chemotherapy treatments.

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

Absence of significant donor (product)-specific anti-HLA antibodies (DSA)

Exclusion Criteria

I had a stem cell transplant within the last 6 months.

My cancer has spread to my brain or spinal cord.

My bone marrow is less active than normal for my age.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive lymphodepletion with ALLO-647, fludarabine, and cyclophosphamide or fludarabine and cyclophosphamide alone

1-2 weeks

CAR T Cell Therapy

Participants receive ALLO-501A CAR T cell infusion following lymphodepletion

1 week

Follow-up

Participants are monitored for safety and effectiveness after CAR T cell therapy

4 weeks

Treatment Details

Interventions

• ALLO-501A
• ALLO-647

Trial Overview The EXPAND study is testing whether adding ALLO-647 to the usual drugs fludarabine and cyclophosphamide helps improve outcomes when given before CAR T cell therapy (ALLO-501A) in patients whose large B-cell lymphoma has relapsed or is resistant to treatment.

Participant Groups

Group I: Lymphodepletion with fludarabine and cyclophosphamide Experimental Treatment 3 Interventions

ALLO-501A CAR T cells infused following lymphodepletion

Group II: Lymphodepletion with ALLO-647, fludarabine, and cyclophosphamide Experimental Treatment 4 Interventions

ALLO-501A CAR T cells infused following lymphodepletion

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

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]

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 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]

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]

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]

Lisocabtagene maraleucel (liso-cel), a CAR T-cell therapy targeting CD-19, achieved a 73% objective response rate and a 53% complete remission rate in patients with large B-cell lymphoma who had undergone a median of 3 prior therapies.

In the second-line treatment setting, liso-cel demonstrated superior event-free survival compared to standard care, highlighting its potential as a significant option for patients with relapsed or refractory large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. Mohty, R., Moreno Vanegas, Y., Chavez, JC., et al.[2023]

Adoptive T cell therapy using anti-CD19-CAR5-T cells, which secrete anti-PD-L1, showed improved effectiveness in killing aggressive B cell lymphomas compared to traditional anti-CD19-CAR-T cells, especially at low effector-to-target ratios.

The study demonstrated that anti-CD19-CAR5-T cells not only proliferated better but also enhanced cytotoxicity against CD19+/PD-L1high tumor cells, suggesting a promising new approach for treating difficult-to-treat B cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T cells secreting anti-PD-L1 single-chain variable fragment attenuate PD-L1 mediated T cell inhibition. Yuti, P., Wutti-In, Y., Sawasdee, N., et al.[2022]

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]

References

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. 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]

4. England pubmed.ncbi.nlm.nih.gov

CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review. [2023]

5. 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]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

8. 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]

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

Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T cells secreting anti-PD-L1 single-chain variable fragment attenuate PD-L1 mediated T cell inhibition. [2022]

13. 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]