ALLO-715 CAR T Cells for Multiple Myeloma

(UNIVERSAL Trial)

Not currently recruiting at 11 trial locations

Overseen By Allogene Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allogene Therapeutics

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: CNS disorder, Thyroid disorder, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALLO-715, a type of CAR T-cell therapy, for individuals with multiple myeloma—a type of blood cancer—who have not had success with other treatments. Researchers aim to determine the safety and effectiveness of ALLO-715, both with and without another drug called Nirogacestat. Suitable participants have multiple myeloma that has not responded to at least three different treatments. The trial seeks to assess the treatment's effectiveness and the body's response. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that ALLO-715 is likely to be safe for humans?

Research has shown that ALLO-715, a ready-to-use CAR T cell therapy, might help treat multiple myeloma. In earlier studies, 88% of patients experienced serious side effects, with cytokine release syndrome (CRS) being the most common, occurring in about 56% of patients. CRS involves an overly active immune response, but only one case was severe.

Despite the side effects, these results provide researchers with insights into how well patients can tolerate ALLO-715. As this treatment remains in the early testing stages, researchers are primarily focused on safety. These studies are crucial for ensuring the treatment's safety before broader use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy and stem cell transplants, ALLO-715 is a CAR T-cell therapy designed to target cancer cells more precisely. Researchers are excited about ALLO-715 because it uses engineered immune cells to recognize and destroy myeloma cells, potentially offering a more targeted and effective approach. This treatment also promises a shorter manufacturing time since the cells are derived from healthy donors rather than the patient's own cells, which could make it more accessible and timely for patients. Additionally, the combination with ALLO-647 and nirogacestat might enhance the efficacy and durability of the response, setting it apart from current options.

What evidence suggests that ALLO-715 might be an effective treatment for multiple myeloma?

Research has shown that ALLO-715, a type of CAR T-cell therapy, may help treat multiple myeloma, a type of blood cancer. In one study, about 56% of patients responded positively, with 35% experiencing a significant reduction in cancer activity. On average, the benefits lasted about 8.3 months. In this trial, participants will receive a combination of ALLO-647, ALLO-715, and Nirogacestat. These results suggest that ALLO-715 could be a safe and effective option for people whose multiple myeloma has returned or is difficult to treat. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Patients unwilling to participate in an extended safety monitoring period

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-reports-positive-initial-results-phase-1

Press Release Allogene Therapeutics Reports Positive Initial Results from Phase 1 UNIVERSAL Study of ALLO-715 AlloCAR T™ Cell Therapy in Relapsed/Refractory Multiple Myeloma ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04093596

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T ... 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 ...

3. nature.com nature.com/articles/s41408-024-01191-8

CAR-T cell therapy in Multiple Myeloma: current status and ... In the phase 1 UNIVERSAL trial, 43 patients were treated with escalating doses of ALLO-715 alongside fludarabine at 90 mg/m2, cyclophosphamide ...

4. network.nmdp.org network.nmdp.org/training-education/catalog/allogeneic-car-t-cell-therapy-may-be-a-safe-and-feasible-treatment-for-relapsed-refractory-mult

Allogeneic CAR-T cell therapy may be a safe and feasible ... Early data showed that 56% of patients responded, with 35% having a good partial response. This study suggests allogeneic CAR T-cell therapy may be a safe, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36690811/

Allogeneic BCMA-targeting CAR T cells in relapsed ... - PubMed The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma. © 2023.

6. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-publication-nature-medicine-data

Press Release ALLO-715 is the first allogeneic anti-BCMA CAR T to demonstrate safety, efficacy and durability with off-the-shelf convenience in multiple myeloma.

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4620/491177/Universal-Updated-Phase-1-Data-Highlights-Role-of

Universal Updated Phase 1 Data Highlights Role of ... As of June 22, 2022, 53 pts were enrolled; 98% of pts receiving LD were treated with ALLO-715 with one remaining patient (2%) pending ALLO-715 ...