CAR-T Therapy for Multiple Myeloma

Recruiting at 55 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: IMiDs, Proteasome inhibitors, Anti-CD38 antibodies

Must not be taking: BCMA CAR-T, BCMA antibodies

Disqualifiers: Plasma cell leukemia, POEMS syndrome, 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: 1

Duration: 1 day (infusion)

146 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called PHE885, a type of CAR-T cell therapy, to evaluate its effectiveness and safety for individuals with multiple myeloma that has returned or is unresponsive to other treatments. Multiple myeloma is a cancer affecting plasma cells in the bone marrow. The trial targets individuals who have tried at least three different treatments without success, including specific drugs and therapies. Participants should have experienced disease progression and be unable to benefit from their last treatment regimen. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

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

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that PHE885, a type of CAR-T cell therapy for multiple myeloma, is generally safe. In earlier research with patients who had already received many treatments, PHE885 was well-tolerated, with no unexpected safety issues reported. While some side effects may occur, they are typical for this kind of therapy. The treatment uses specially engineered cells to fight cancer and appears to work without causing unusual harm. ^{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 involve chemotherapy, immunomodulatory drugs, and proteasome inhibitors, PHE885 is a CAR-T cell therapy that offers a personalized approach. PHE885 works by genetically modifying a patient's own T cells to specifically target and attack myeloma cells, which is a different mechanism from traditional therapies. Researchers are excited about PHE885 because it has the potential to provide longer-lasting remission and may offer a new option for patients who have not responded well to existing treatments.

What evidence suggests that PHE885 might be an effective treatment for multiple myeloma?

Research has shown that PHE885, a new CAR-T cell therapy, may help treat multiple myeloma. In earlier studies, PHE885 proved effective for patients with severe forms of the disease who had already tried many other treatments. This therapy targets a protein called BCMA on myeloma cells, enhancing the immune system's ability to attack the cancer. Patients who received PHE885 experienced significant improvements without unexpected safety issues. These findings suggest that PHE885 could be a viable option for those whose multiple myeloma has returned or not responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with multiple myeloma that's come back or hasn't responded after at least three treatments, including specific drugs like IMiDs and proteasome inhibitors. They must have measurable disease, be in good physical condition (ECOG 0-1), and have cells ready for making the CAR-T therapy. Not eligible if they've had certain other myeloma treatments, recent bone marrow transplants, plasma cell leukemia, CNS involvement by cancer, autoimmune neurological conditions, or poor organ function.

Inclusion Criteria

I have completed at least 3 treatment cycles for my condition.

My leukapheresis material is approved for use.

My condition worsened within 2 months after my last treatment.

Exclusion Criteria

I have been diagnosed with POEMS syndrome.

I have previously received genetically modified cell therapy, including BCMA CAR-T.

I have previously received BCMA-targeted therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PHE885 CAR-T cell therapy as a single agent

1 day (infusion)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits as per protocol

Long-term follow-up

Participants are offered long-term follow-up for lentiviral vector safety

15 years

What Are the Treatments Tested in This Trial?

Interventions

• PHE885

Trial Overview The trial is testing PHE885 CAR-T therapy on adults with relapsed/refractory multiple myeloma. It's a Phase II study to see how well it works and its safety when made using a new process. Participants will receive this single-agent treatment to evaluate its effectiveness against their cancer.

How Is the Trial Designed?

Group I: PHE885 Experimental Treatment 1 Intervention

Patients will receive PHE885

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown promising results in treating multiple myeloma, with high-quality responses observed in heavily pretreated patients, and ongoing Phase 3 trials are comparing its efficacy against standard treatments.

While CAR T-cell therapy can lead to sustained responses in some patients, most eventually relapse due to factors like loss of CAR T cells or antigen expression, prompting research into improving CAR design and safety measures, such as suicide gene systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. van de Donk, NWCJ., Usmani, SZ., Yong, K.[2021]

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]

CAR T cell therapies targeting BCMA have shown promising results in early clinical trials for treating multiple myeloma, indicating potential for long-lasting remissions.

However, these therapies are associated with significant toxicities, including cytokine release syndrome and neurotoxicity, highlighting the need for ongoing research to improve their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell immunotherapy for multiple myeloma: A review of current data and potential clinical applications. Susanibar Adaniya, SP., Cohen, AD., Garfall, AL.[2020]

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]

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]

In a study of five patients with relapsed multiple myeloma receiving anti-BCMA CAR-T cell therapy, four achieved complete remission within one month, indicating strong efficacy of this treatment.

The levels of soluble BCMA (sBCMA) in plasma decreased significantly after CAR-T infusion, suggesting that sBCMA could serve as a useful biomarker for monitoring treatment response in multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. Seipel, K., Porret, N., Wiedemann, G., 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]

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]

The introduction of second-generation proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has significantly improved survival rates for multiple myeloma patients, but many still relapse, highlighting the need for new therapies.

B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy shows promise as a new treatment option for patients with multiple myeloma who are resistant to current standard therapies, offering a different mechanism of action to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. Rodríguez-Otero, P., Prósper, F., Alfonso, A., 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]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8004

Updated phase I study results of PHE885, a T-Charge ... T-Charge manufactured PHE885 produced high response rates with no unexpected safety findings in heavily pretreated RRMM pts with aggressive disease.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430604/

PHASE I STUDY DATA UPDATE OF PHE885, A FULLY ... This multicenter, open-label study (NCT04318327) characterizes the safety and efficacy of PHE885 manufactured using the novel T-Charge TM platform.

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

CAR-T cell therapy in Multiple Myeloma: current status and ... Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05172596

Study Details | NCT05172596 | PHE885 CAR-T Therapy in ... This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cell therapy, manufactured with a new process. The CAR-T cell ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11101341/

CAR T therapies in multiple myeloma: unleashing the future A cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM).

6. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-024-00634-5

Updates on CAR T cell therapy in multiple myeloma In this review, we provide an overview of the effectiveness of currently available CAR T-cell treatments for MM, explore the primary resistance mechanisms to ...