CAR T Cell Therapy for Multiple Myeloma

(QUINTESSENTIAL Trial)

Recruiting at88 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Must be taking: Immunomodulatory, Proteasome inhibitors

Disqualifiers: CNS involvement, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the effectiveness and safety of Arlocabtagene Autoleucel (BMS-986393) in participants with relapsed or refractory multiple myeloma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions a 'washout period' (time without taking certain medications) for some treatments before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment BMS-986393, CC-95266 for multiple myeloma?

Research shows that CAR T-cell therapies targeting BCMA (a protein found on myeloma cells) are highly effective in treating multiple myeloma, with response rates between 60% to 100% in patients with relapsed or refractory disease. These therapies have shown the potential to induce long-term remissions and are considered promising for overcoming drug resistance in multiple myeloma. ^{1 2 3 4 5}

What is known about the safety of CAR T Cell Therapy for Multiple Myeloma?

CAR T Cell Therapy for Multiple Myeloma has shown some safety concerns, including cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (nerve damage), which can be severe but are usually reversible. Other common side effects include various blood cell deficiencies like leukopenia (low white blood cell count), neutropenia (low neutrophil count), and thrombocytopenia (low platelet count). However, these therapies have generally been considered to have a good safety profile in clinical trials. ^{1 2 6 7 8}

How is the CAR T Cell Therapy BMS-986393 different from other treatments for multiple myeloma?

BMS-986393 is a CAR T cell therapy that targets the BCMA antigen on myeloma cells, offering a unique approach by engineering a patient's own T cells to attack the cancer, which is different from traditional chemotherapy or stem cell transplants. This therapy has shown promising results in achieving deep remissions in patients with relapsed or refractory multiple myeloma, a condition where other treatments often fail. ^{1 2 3 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with multiple myeloma that has come back or hasn't responded to treatment. Specific details about who can join are not provided, but typically participants need to meet certain health standards and have a history of the condition being studied.

Inclusion Criteria

Participants must have measurable disease during screening

I am fully active or can carry out light work.

I have been diagnosed with multiple myeloma according to IMWG standards.

Exclusion Criteria

I haven't had treatments targeting GPRC5D or other MM treatments without the needed break before leukapheresis.

Other protocol-defined Inclusion/Exclusion criteria apply

My multiple myeloma has affected or previously affected my brain or spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Arlocabtagene Autoleucel (BMS-986393) CAR T Cell Therapy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• BMS-986393 (CAR T-cell Therapy)

Trial Overview The study is testing BMS-986393, which is a CAR T cell therapy targeting GPRC5D, a protein often found on myeloma cells. The goal is to see how effective and safe this therapy is in treating patients whose multiple myeloma has relapsed or resisted other treatments.

Participant Groups

Group I: Arlocabtagene Autoleucel (BMS-986393) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Findings from Research

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]

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]

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]

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]

C-CAR088, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 96.4% in patients with relapsed or refractory multiple myeloma, with significant rates of complete response (10.7%) and stringent complete response (46.4%).

The therapy showed a favorable safety profile, with 93.5% of patients experiencing cytokine release syndrome (CRS) that was manageable and reversible, and no dose-limiting toxicities reported across the tested dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Qu, X., An, G., Sui, W., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy shows great promise for treating relapsed/refractory multiple myeloma (RRMM), building on its success in other blood cancers like acute lymphocytic leukemia and diffuse large B-cell lymphoma.

The review highlights six potential target antigens for CAR T-cell therapy in multiple myeloma and discusses the safety profiles of existing CAR T-cell treatments, indicating a significant advancement in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. Huang, H., Wu, HW., Hu, YX.[2020]

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]

References

1. 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]

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

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. [2019]

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

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

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

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. [2021]

5. 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]

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

CAR T-cell therapy for multiple myeloma: state of the art and prospects. [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. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. [2020]

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

CARs in the Lead Against Multiple Myeloma. [2018]