BCMA CAR-T Cell Therapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Immunomodulatory imide drugs

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Pregnancy, Active infections, Second malignancies, others

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

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals with multiple myeloma, a type of blood cancer that often resists regular treatments. The therapy involves altering a person's T cells (a type of immune cell) to enhance their ability to target and destroy cancer cells. The trial focuses on ensuring the safety of administering these modified T cells, known as Anti-BCMA CAR T cells, to patients. It is open to adults with multiple myeloma that hasn't responded to standard treatments and who have tried at least three different therapies. As a Phase 1 trial, participants will be among the first to receive this innovative treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take systemic corticosteroids above a certain dose within 2 weeks before certain procedures, and you must wait at least 14 days after any prior systemic therapy before starting the trial's conditioning regimen.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that anti-BCMA CAR T-cell therapy is generally safe for most people with multiple myeloma, a type of blood cancer. Studies have found that it reduces side effects and improves patient outcomes. Some research even indicates quick tumor shrinkage and good survival rates. This treatment is already approved for some patients with recurring forms of this cancer, suggesting its safety in these cases. However, since this is an early trial, the researchers are closely monitoring the treatment's safety to ensure it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about anti-BCMA CAR-T cell therapy for multiple myeloma because it uses a groundbreaking approach that harnesses the body's own immune system to combat cancer. Unlike traditional treatments like chemotherapy and stem cell transplants, this therapy involves genetically modifying a patient's T cells to specifically target and destroy multiple myeloma cells by recognizing the BCMA protein on their surface. This precision targeting could potentially lead to more effective and lasting responses with fewer side effects. Additionally, the dose escalation and expansion phases allow for optimizing the treatment's effectiveness, potentially offering new hope for patients who have exhausted other options.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that anti-BCMA CAR T-cell therapy holds great promise for treating multiple myeloma. In this trial, participants will receive conditioning chemotherapy followed by anti-BCMA CAR T-cell therapy. Studies have found that this treatment achieves high success rates, with over 90% of patients experiencing positive results. For patients who have undergone many treatments, this therapy has effectively reduced cancer cells and improved survival rates. Early findings also suggest it is safe, with manageable side effects. However, some patients may eventually see the disease return. Overall, this treatment offers hope for those who have not responded to standard therapies. ^{1 2 3 4 6}

Who Is on the Research Team?

James N Kochenderfer, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18-73 with multiple myeloma resistant to standard treatments, who have tried at least three different therapies including IMiDs and proteasome inhibitors. Participants must not be HIV or hepatitis positive, should have adequate organ function, and agree to use birth control. Those with certain other health conditions or treatments are excluded.

Inclusion Criteria

My platelet count is above 55,000 without recent transfusions.

I have stored blood cells not modified by gene therapy.

Less than half of my bone marrow cells are plasma cells.

Exclusion Criteria

I need urgent treatment because my tumor is pressing on my spine or other organs.

I have multiple myeloma and no other cancer needing treatment in the last 3 years, except for certain skin cancers.

I have an active autoimmune disease like psoriasis or rheumatoid arthritis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Apheresis

Participants undergo apheresis to collect T cells for genetic modification

1 day

1 visit (in-person)

Chemotherapy Conditioning

Participants receive cyclophosphamide and fludarabine to deplete lymphocytes

3 days

3 visits (in-person)

T-cell Infusion

Genetically modified T cells are infused into participants

1 day

1 visit (in-person)

Inpatient Monitoring

Participants are monitored for toxicity following T-cell infusion

9 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

8 visits (in-person)

Long-term Follow-up

Participants' blood is collected regularly over several years for long-term monitoring

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Anti-BCMA CAR T cells

Trial Overview The trial is testing a gene therapy using the patient's own T cells that are modified in the lab to target cancer cells more effectively. It includes chemotherapy drugs Cyclophosphamide and Fludarabine followed by infusion of these engineered T cells.

How Is the Trial Designed?

Group I: 2/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells expansion phase Experimental Treatment 3 Interventions

6.0x10\^6 dose (maximum feasible dose) of CAR T Cells + Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3

Group II: 1/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells dose escalation Experimental Treatment 3 Interventions

Patients will receive escalating doses (up to 5 planned) of CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg /m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

BCMA-CAR-T cells, engineered to target the B-cell maturation antigen (BCMA), demonstrated strong cytotoxic effects against BCMA-positive myeloma cells in vitro, significantly reducing the number of residual cancer cells compared to control groups.

In a mouse model of multiple myeloma, treatment with BCMA-CAR-T cells significantly increased survival time, indicating their potential as an effective therapy for patients with BCMA-positive multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]. Zhong, MJ., Xu, YX., Xing, HY., et al.[2020]

In a first-in-humans clinical trial involving 16 patients with heavily treated multiple myeloma, CAR-BCMA T cells demonstrated an impressive overall response rate of 81%, with 63% achieving very good partial or complete responses.

The treatment was associated with significant anti-myeloma activity, including eradication of bone marrow myeloma and resolution of soft-tissue plasmacytomas, although some patients experienced severe but reversible cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Brudno, JN., Maric, I., Hartman, SD., et al.[2019]

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]

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]

The newly developed BCMA-targeted fourth-generation CAR-T cells (BCMA-7 × 19 CAR-T cells) showed enhanced capabilities in expanding, differentiating, migrating, and killing cancer cells compared to previous CAR-T therapies, indicating improved efficacy against refractory/relapsed multiple myeloma (R/R MM).

In a first-in-human clinical trial involving two patients, BCMA-7 × 19 CAR-T cells demonstrated promising safety and efficacy, with one patient achieving complete remission (CR) and the other a very good partial response (VGPR) after just one dose, and only mild cytokine release syndrome observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Duan, D., Wang, K., Wei, C., et al.[2021]

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[2023]

In a study involving 16 patients with relapsed or refractory multiple myeloma, the bispecific CS1-BCMA CAR-T cells showed a high overall response rate of 81%, with 38% achieving a stringent complete response, indicating strong efficacy in targeting this challenging cancer.

The treatment had a manageable safety profile, with 38% of patients experiencing mild cytokine release syndrome and significant hematological adverse events, but no neurological toxicities were reported, suggesting a favorable safety outcome for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Li, C., Xu, J., Luo, W., et al.[2023]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11021094/

Exploring the efficacy and safety of anti-BCMA chimeric ... Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/18/4624/546157/Sequential-BCMA-CAR-T-cell-therapy-in-refractory

Sequential BCMA CAR T-cell therapy in refractory multiple ... These therapies have demonstrated unprecedented responses in heavily pretreated patients with RRMM, with overall response rates (ORRs) >90%, and ...

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

CAR-T cell therapy in Multiple Myeloma: current status and ... The phase 1 MCARH109 study enroled 17 patients, almost half of whom had received prior BCMA CAR-T cell therapy.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19541

Outcomes with non-BCMA CAR T cell therapy for multiple ... Anti-BCMA CAR T cell therapy for MM has exhibited deep responses, but patients eventually get relapsed disease, which requires the need to ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1817226

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or ... In conclusion, in a heavily pretreated population of patients with multiple myeloma, bb2121 showed promising efficacy at dose levels of 150×106 or more CAR+ T ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40924178/

Comparative efficacy and safety of BCMA-targeted CAR T ... CAR-T therapies showed a higher overall response rate (ORR) of 84% and CR/stringent CR (CR/sCR) of 55%, compared to 65% and 41%, respectively, ...