CAR-T Cell Therapy for Multiple Myeloma

Recruiting at 12 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Chemotherapy, Antineoplastics, Immunotherapies, others

Disqualifiers: Genetically modified cells, HSCT, others

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

Compensation: Varies

Number of Visits: Unknown

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells will be investigated as a single agent in multiple myeloma

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy or any anti-cancer therapies (except for specific trial-related chemotherapy) at least 2 weeks before apheresis (a procedure to collect blood cells). Additionally, you must stop taking certain antibodies or immunotherapies 3 to 4 weeks before apheresis.

What data supports the effectiveness of the treatment PHE885 for multiple myeloma?

Research shows that CAR T-cell therapy, which includes treatments like PHE885, has shown promise in treating multiple myeloma, especially for patients who have not responded to other treatments. These therapies target specific proteins on cancer cells, leading to high response rates in patients with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for treating multiple myeloma?

CAR-T cell therapy for multiple myeloma has shown a manageable safety profile in clinical trials, with common side effects including cytokine release syndrome (a reaction causing fever and flu-like symptoms) and neurotoxicity (nerve-related issues). Most side effects are mild to moderate, and severe cases are less common. ^{6 7 8 9 10}

How is the treatment PHE885 different from other treatments for multiple myeloma?

PHE885 is a CAR-T cell therapy, which is a novel treatment that uses genetically modified T cells to target and destroy cancer cells in multiple myeloma. Unlike traditional treatments, CAR-T therapy specifically targets B-cell maturation antigen (BCMA) on myeloma cells, offering a new mechanism of action for patients who have relapsed or are resistant to existing therapies. ^{1 11 12 13 14}

Eligibility Criteria

This trial is for adults with Multiple Myeloma who've had at least two prior treatments, including specific drugs like IMiDs and proteasome inhibitors. They should have a performance status of 0 or 1 if previously treated, or up to 2 if newly diagnosed after standard therapy. Participants must not have had any genetic cell therapies before, nor certain cancer treatments close to joining the study.

Inclusion Criteria

You have a condition that can be measured according to the study's guidelines.

My leukapheresis material is approved for use.

My blood test results are within normal ranges.

Exclusion Criteria

I have previously received a genetic cell therapy but not BCMA-directed bi-specific antibodies or ADC.

I haven't had chemotherapy or other cancer treatments except for LD chemotherapy in the last 2 weeks.

I have had my own stem cell transplant within the last 6 weeks or have never had a stem cell transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Relapsed and/or refractory multiple myeloma patients receive PHE885 to study safety and tolerability

28 days

Multiple visits for monitoring and dose administration

Dose Evaluation (Part B)

Newly diagnosed multiple myeloma patients receive PHE885 to study safety and tolerability

28 days

Multiple visits for monitoring and dose administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits for response assessment and monitoring

Treatment Details

Interventions

• PHE885

Trial Overview The trial tests PHE885, a new type of CAR-T cell therapy targeting BCMA on myeloma cells. It's a first-in-human study assessing how safe it is and its initial effectiveness against multiple myeloma as a single agent treatment.

Participant Groups

Group I: PHE885 (Part B) Experimental Treatment 1 Intervention

Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.

Group II: PHE885 (Part A) Experimental Treatment 1 Intervention

Relapsed and/or refractory multiple myeloma (r/r MM) 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

Findings from Research

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]

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 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 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]

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]

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]

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]

In a study of 22 patients with relapsed or refractory multiple myeloma, a combination of anti-BCMA and anti-CD38 CAR-T cell therapy showed a high overall response rate of 90.9%, with over half achieving a complete response.

While the treatment demonstrated significant efficacy, it also resulted in cytokine release syndrome in 72.7% of patients, indicating the need for careful monitoring of side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. Zhang, H., Liu, M., Xiao, X., et al.[2022]

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]

The dual-CAR T-cell therapy targeting CD138 and CD38 showed a significant anti-multiple myeloma response, resulting in a median survival of 97 days in treated mice compared to 31 days in the control group, indicating its potential efficacy.

This approach demonstrated increased specificity for cancer cells coexpressing both antigens while minimizing off-target effects on healthy tissues, suggesting a safer treatment option for multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity. Globerson Levin, A., Rawet Slobodkin, M., Waks, T., et al.[2021]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. [2023]

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

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

3. 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]

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

Analysis of patient-reported experiences up to 2 years after receiving idecabtagene vicleucel (ide-cel, bb2121) for relapsed or refractory multiple myeloma: Longitudinal findings from the phase 2 KarMMa trial. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. [2021]

7. 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]

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

A combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. [2022]

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

Lentiviral transduction of primary myeloma cells with CD80 and CD154 generates antimyeloma effector T cells. [2017]

12. England pubmed.ncbi.nlm.nih.gov

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

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

Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity. [2021]

14. England pubmed.ncbi.nlm.nih.gov

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