CAR-T Therapy for Multiple Myeloma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Ineligible for CAR-T, Myeloid neoplasm

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

82 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial evaluates the impact of preexisting and therapy-emergent germline and somatic variants on cytopenia in patients with multiple myeloma or CD19 positive lymphoproliferative disorder (LPD) following chimeric antigen receptor T-cell (CAR-T) therapy. The most common adverse event after CAR-T therapy is lower than normal blood cells (cytopenia) and up to one third of patients experience cytopenia that last longer than 30 days post-infusion. Germline and somatic variants are changes in genes found using cancer genomic tests. Cancer genetic/genomic testing is a series of tests that find specific changes in cancer cells or in blood deoxyribonucleic acid. Identifying gene mutations may help identify the risk of cytopenia in patients with multiple myeloma or CD19 positive LPD following CAR-T therapy.

Do I have to stop taking my current medications for the trial?

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

What data supports the effectiveness of CAR-T therapy for multiple myeloma?

CAR-T therapy, specifically ciltacabtagene autoleucel, has shown promising results in patients with relapsed or refractory multiple myeloma, leading to early and lasting improvements in their condition. Additionally, idecabtagene vicleucel, another CAR-T therapy, has demonstrated notable effectiveness and safety in treating multiple myeloma, gaining FDA approval for patients who have not responded to other treatments. ^{1 2 3 4 5}

What is known about the safety of CAR-T therapies in humans?

CAR-T therapies, like axicabtagene ciloleucel and tisagenlecleucel, have been approved for use and have shown good results, but they can also cause side effects. These side effects can include serious reactions like cytokine release syndrome (a severe immune response) and neurological issues, which require careful management by healthcare providers. ^{1 5 6 7 8}

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

CAR-T therapy is unique because it involves modifying a patient's own T cells (a type of immune cell) to specifically target and kill cancer cells, offering a new approach for patients who have not responded to other treatments. This therapy has shown promising results in achieving deep and lasting remissions in patients with relapsed or refractory multiple myeloma, where traditional treatments have failed. ^{2 4 9 10 11}

Research Team

Mithun Shah, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for patients with multiple myeloma or CD19+ lymphoproliferative disorders who have undergone CAR-T therapy and are experiencing low blood cell counts. The study aims to understand the genetic factors contributing to this condition.

Inclusion Criteria

Willingness to provide mandatory bone marrow aspirate specimens for correlative research

Willingness to provide mandatory hair follicle specimens for correlative research

Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria

I was diagnosed with a blood cancer before receiving CAR-T therapy.

I am not eligible for CAR-T cell therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-Treatment Sample Collection

Patients undergo bone marrow aspiration and hair, buccal, and saliva sample collection up to 14 days prior to lymphodepleting therapy

2 weeks

1 visit (in-person)

Treatment

Patients receive CAR-T therapy

1 day

1 visit (in-person)

Follow-up

Patients undergo clinical follow-up on day 90 post-CAR-T therapy. Patients with unexplained cytopenia are followed up every 90 days for up to 2 years until resolution. Patients without unexplained cytopenia are followed clinically for up to 2 years.

Up to 2 years

Multiple visits (in-person)

Treatment Details

Interventions

• CAR-T Therapy

Trial Overview The trial involves collecting biospecimens, genetic counseling and testing, bone marrow aspiration, reviewing electronic health records, and follow-up visits to investigate how gene variants affect blood cell count after CAR-T therapy.

Participant Groups

Group I: Supportive care (bone marrow aspiration, CFU) Experimental Treatment 6 Interventions

Patients undergo bone marrow aspiration and hair, buccal, saliva sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during on day 90. Additionally, patients receive a genetic counselor consultation on study.

CAR-T Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Approved in European Union as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

Ciltacabtagene autoleucel (cilta-cel) therapy significantly improved health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma, with a notable decrease in reported symptoms such as pain and fatigue from 85.2% at baseline to 22.2% by Day 184.

The majority of patients (70.8%) felt that cilta-cel met or exceeded their treatment expectations, highlighting its efficacy and the positive impact of a long treatment-free period on their overall health perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. Cohen, AD., Hari, P., Htut, M., et al.[2023]

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

Chimeric antigen receptor (CAR) T-cell therapy, such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T-cells that target the CD19 antigen.

This collaborative work provides practical guidance for healthcare centers on how to select patients for these commercially available CAR T-cell therapies, ensuring appropriate use and maximizing treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. Beauvais, D., Bachy, E., Baruchel, A., et al.[2021]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., 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]

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.

The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. [2021]

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

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. [2021]

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

The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

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

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. [2022]

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

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

10. England pubmed.ncbi.nlm.nih.gov

CAR T cell therapy in multiple myeloma, where are we now and where are we heading for? [2023]

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

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]