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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Multiple myeloma is a cancer of the blood plasma cells. It usually becomes resistant to standard treatments. Researchers have developed a procedure called gene therapy. It uses a person's own T cells, which are part of the immune system. The cells are changed in a lab and then returned to the person. Researchers hope the changed T cells will be better at recognizing and killing tumor cells. Objective: To test the safety of giving changed T cells to people with multiple myeloma. Eligibility: Adults ages 18-73 who have been diagnosed with multiple myeloma that has not been controlled with standard therapies. Design: Participants will be screened with: Medical history Physical exam Blood tests Heart function tests Bone marrow sample taken by needle in a hip bone. Scan of the chest, abdomen, and pelvis. They may have a brain scan. Pregnancy test Participants will have apheresis. Blood will be removed through an arm vein. The blood will be separated, and T cells removed. The rest of the blood will be returned through a vein in the other arm. Participants will have a central line placed in a large vein in the arm or chest. Participants will get 2 chemotherapy drugs by the central line over 3 days. Two days later, participants will get the changed T cells by the central line. They will stay in the hospital at least 9 days. Participants must stay near the hospital for 2 weeks. Participants will have 8 follow-up visits over the next year for blood and urine tests. They may have scans. Participants blood will be collected regularly over the next several years.

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.

What data supports the effectiveness of the BCMA CAR-T cell treatment for multiple myeloma?

Research shows that BCMA CAR-T cells are a powerful treatment for multiple myeloma, with studies reporting high response rates, including partial and complete remissions, even in patients who have tried many other treatments. This therapy has shown substantial activity against heavily treated relapsed or refractory multiple myeloma, with some patients achieving minimal residual disease-negative status, meaning no detectable cancer cells remain. ^{1 2 3 4 5}

Is BCMA CAR-T cell therapy safe for humans?

BCMA CAR-T cell therapy has shown a manageable safety profile in clinical trials for multiple myeloma, with common side effects including mild cytokine release syndrome (a reaction that can cause fever and low blood pressure) and some blood-related issues like low white blood cell counts. Severe side effects were rare and reversible, indicating that the treatment is generally safe for humans. ^{1 5 6 7 8}

How is BCMA CAR-T cell therapy different from other treatments for multiple myeloma?

BCMA CAR-T cell therapy is unique because it uses genetically modified T cells to specifically target and destroy multiple myeloma cells by recognizing a protein called BCMA on their surface. This approach is different from traditional treatments as it involves reprogramming the patient's own immune cells to fight the cancer, offering a novel mechanism of action. ^{1 2 5 9 10}

Research Team

James N Kochenderfer, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

References

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

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? [2023]

2. 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]

3. 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]

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

Determinants of response and mechanisms of resistance of CAR T-cell therapy in multiple myeloma. [2023]

5. United States 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. [2019]

6. Switzerland 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. [2023]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. China pubmed.ncbi.nlm.nih.gov

[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]. [2020]