ALLO-715 CAR T Cells for Multiple Myeloma

(UNIVERSAL Trial)

Recruiting at 11 trial locations

Overseen By Allogene Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allogene Therapeutics

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

132 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the UNIVERSAL study is to assess the safety, efficacy, cell kinetics, and immunogenicity of ALLO-715 with or without Nirogacestat in adults with relapsed or refractory multiple myeloma after a lymphodepletion regimen of ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking strong/moderate CYP3A4 inhibitors or strong CYP3A4 inducers, you may need to stop them 14 days before starting nirogacestat.

What data supports the effectiveness of the treatment ALLO-715 CAR T Cells for Multiple Myeloma?

Research shows that CAR T-cell therapy, which includes treatments like ALLO-715, has been effective in treating multiple myeloma, especially in patients who have not responded to other treatments. Although specific data on ALLO-715 is limited, similar CAR T-cell therapies targeting myeloma antigens have shown promising results in clinical trials. ^{1 2 3 4 5}

Is ALLO-715 CAR T cell therapy safe for humans?

ALLO-715 CAR T cell therapy has been tested in humans with multiple myeloma, showing a manageable safety profile. Common side effects included cytokine release syndrome (a reaction that can cause fever and low blood pressure) and infections, but severe cases were rare. Overall, the therapy appears to be safe, with most side effects being mild to moderate. ^{6 7 8 9 10}

What makes ALLO-715 treatment unique for multiple myeloma?

ALLO-715 is a type of CAR T cell therapy, which is a novel approach that uses genetically modified immune cells to target and destroy cancer cells. Unlike traditional treatments, CAR T cell therapy specifically targets antigens like BCMA on myeloma cells, offering a more personalized and potentially effective treatment option for patients with multiple myeloma. ^{1 4 5 7 11}

Eligibility Criteria

Adults with relapsed or refractory multiple myeloma who have tried at least three prior treatments, including specific inhibitors and antibodies, can join this trial. They must be in good physical condition with no significant CNS disorders, HIV, hepatitis B or C infections, recent stem cell transplants, or conditions affecting drug absorption.

Inclusion Criteria

You do not have antibodies against the donor's cells.

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

My multiple myeloma has returned or didn't respond to treatment, and tests show it's still present.

Exclusion Criteria

I do not have conditions that affect how my body absorbs medication.

I have not had treatments like anti-BCMA, gene therapy, or T cell therapy.

Patients unwilling to participate in an extended safety monitoring period

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo a lymphodepletion regimen with ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone

33 days

Treatment

Participants receive ALLO-715 with or without Nirogacestat following lymphodepletion

28 days

Follow-up

Participants are monitored for safety, efficacy, and cellular kinetics of ALLO-715

up to 60 months

Treatment Details

Interventions

• ALLO-715

Trial Overview The UNIVERSAL study is testing the safety and effectiveness of ALLO-715 CAR T cells alone or combined with Nirogacestat following a lymphodepletion regimen. This involves using ALLO-647 along with fludarabine and/or cyclophosphamide to prepare the body for treatment.

Participant Groups

Group I: ALLO-647, ALLO-715, Nirogacestat Experimental Treatment 5 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

Chimeric antigen receptor (CAR)-T cell therapy shows promising efficacy and manageable toxicity in heavily pretreated multiple myeloma patients, with over 50 ongoing clinical trials exploring various CAR-T designs and targets.

The most effective CAR-T therapy so far targets B cell maturation antigen, but challenges remain, including the duration of response and the risk of prolonged cytopenia, necessitating further research to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CAR-T cell therapies for multiple myeloma. Gagelmann, N., Riecken, K., Wolschke, C., et al.[2021]

Multiple myeloma remains an incurable disease, and patients often experience relapses after standard treatments, leading to a poor prognosis.

Chimeric antigen receptor (CAR) T-cell therapy shows promise in improving outcomes for relapsed multiple myeloma, although it is not yet approved for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far-And the Road Ahead. Cowan, AJ., Tuazon, SA., Portuguese, AJ., et al.[2022]

CAR T cell therapy, originally successful for treating leukemia, is now being explored for multiple myeloma, targeting specific antigens like BCMA and CD138.

Preliminary results from clinical trials indicate that CAR T cell therapy shows promise in treating multiple myeloma, although only a limited number of patients have been treated so far.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs in the Lead Against Multiple Myeloma. Ormhøj, M., Bedoya, F., Frigault, MJ., et al.[2018]

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. Wang, Y., Cao, J., Gu, W., et al.[2022]

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

BCMA CAR T-cell therapy has shown impressive response rates of 60% to 100% in patients with relapsed/refractory myeloma, indicating its potential as a highly effective treatment option.

While the therapy can lead to severe but reversible toxicities like cytokine release syndrome and neurotoxicity, ongoing studies aim to enhance its safety and efficacy through combinations with other treatments and gene editing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. Cohen, AD.[2019]

CAR T-cell therapy, specifically BCMA-directed products like idecabtagene vicleucel and ciltacabtagene autoleucel, has been FDA-approved for treating relapsed/refractory multiple myeloma, showing high response rates in patients who have undergone extensive prior treatments.

Despite their effectiveness, these therapies are associated with significant immune-related side effects and relapse rates, highlighting the need for ongoing research to enhance their efficacy and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review. Sadek, NL., Costa, BA., Nath, K., et al.[2023]

HBI0101, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 75% in a phase I study involving 20 heavily pre-treated patients with relapsed/refractory multiple myeloma, with a dose-dependent increase in efficacy observed in higher doses.

The therapy showed a manageable safety profile, with 90% of patients experiencing only mild cytokine release syndrome and no severe toxicities, indicating that HBI0101 could be a safe and effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Asherie, N., Kfir-Erenfeld, S., Avni, B., et al.[2023]

Chimeric antigen receptor (CAR)-modified T cell therapy has shown promising efficacy in treating refractory or relapsed multiple myeloma (MM) in both preclinical and clinical studies, indicating a potential new treatment avenue for this incurable disease.

The toxicities associated with CAR-T cell therapy are manageable, suggesting that this innovative approach could be a safe option for patients with MM, especially as research continues to identify effective targets and improve technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapies for multiple myeloma. Wu, C., Zhang, L., Brockman, QR., et al.[2020]

References

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

Development of CAR-T cell therapies for multiple myeloma. [2021]

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

Chimeric Antigen Receptor T Cells in Multiple Myeloma. [2023]

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

Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far-And the Road Ahead. [2022]

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

CARs in the Lead Against Multiple Myeloma. [2018]

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

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. [2022]

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

Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. [2023]

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

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. [2023]

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

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. [2019]

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

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. [2023]

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

Chimeric antigen receptor T cell therapies for multiple myeloma. [2020]