Dasatinib + Quercetin With CAR-T Therapy for Multiple Myeloma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Anticoagulants, Antiplatelets, Quinolones, CYP3A4/5 inhibitors

Disqualifiers: HIV, Cardiovascular disease, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well giving dasatinib and quercetin with cyclophosphamide, fludarabine and chimeric antigen receptor (CAR)-T cell therapy works in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Quercetin is a compound found in plants that may prevent multiple myeloma from forming. Chemotherapy such as cyclophosphamide and fludarabine are given to help kill any remaining cancer cells in the body and to prepare the bone marrow for CAR-T therapy. Chimeric antigen receptor T-cell Therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving dasatinib and quercetin with cyclophosphamide, fludarabine and CAR-T cell therapy may kill more cancer cells in patients with relapsed or refractory multiple myeloma.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications like strong CYP3A4/5 inhibitors or inducers, therapeutic doses of anticoagulants, or antiplatelet agents. If you are on these, you may need to adjust or stop them before joining the trial.

What data supports the effectiveness of the treatment Dasatinib + Quercetin with CAR-T Therapy for Multiple Myeloma?

CAR-T cell therapies, like ciltacabtagene autoleucel, have shown promise in treating multiple myeloma by targeting specific proteins on cancer cells, leading to significant anti-myeloma activity in early trials. Additionally, polyphenols like quercetin have demonstrated potential to enhance the effects of other cancer treatments, suggesting they might improve outcomes when combined with CAR-T therapy. ^{1 2 3 4 5}

Is the combination of Dasatinib, Quercetin, and CAR-T therapy safe for treating multiple myeloma?

CAR-T cell therapies, which are part of this treatment, have shown an acceptable safety profile in early trials for multiple myeloma, but they can cause side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and infections. Quercetin has been studied for its effects on cancer cells, but specific safety data for its use in combination with Dasatinib and CAR-T therapy is not detailed in the available research. ^{1 3 6 7 8}

How is the treatment with Dasatinib and Quercetin combined with CAR-T therapy different for multiple myeloma?

This treatment is unique because it combines Dasatinib and Quercetin, which have shown potential anti-cancer effects, with CAR-T therapy, a cutting-edge approach that uses modified immune cells to target cancer cells. This combination aims to enhance the effectiveness of CAR-T therapy by potentially overcoming drug resistance and targeting multiple pathways involved in multiple myeloma. ^{1 2 3 6 9}

Research Team

Yi Lin, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with multiple myeloma that has either returned after getting better (relapsed) or hasn't improved with treatment (refractory). Specific eligibility criteria are not provided, but typically include factors like age, overall health, and the specifics of their cancer.

Inclusion Criteria

Life expectancy ≥ 12 weeks

Hemoglobin ≥ 8.0 g/dL

Absolute neutrophil count (ANC) ≥ 1,000/mm^3

Exclusion Criteria

Pregnant, nursing, or unwilling to employ adequate contraception

Receiving other investigational agents for primary neoplasm

Known hypersensitivity or allergy to dasatinib or quercetin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive dasatinib and quercetin orally on days -7 and -6, followed by cyclophosphamide and fludarabine intravenously on days -5 to -3

1 week

Daily visits for drug administration

CAR-T Cell Infusion

Participants receive CAR-T cell therapy intravenously on day 0

1 day

1 visit (in-person)

Post-Treatment Monitoring

Participants receive dasatinib and quercetin on days 28, 29, 58, 59, 88, and 89, and undergo various assessments including CT scan, PET, tumor biopsy, and blood and urine sample collection

3 months

Multiple visits for assessments and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Ciltacabtagene Autoleucel
• Dasatinib
• Quercetin

Trial Overview The study tests dasatinib and quercetin combined with cyclophosphamide, fludarabine, and CAR-T cell therapy. Dasatinib blocks proteins that tell cancer cells to grow; quercetin may prevent cancer formation. The chemotherapy drugs kill remaining cancer cells before the modified T cells are reintroduced to attack the cancer.

Participant Groups

Group I: Treatment (Dasatinib, quercetin, chemotherapy, CAR-T) Experimental Treatment 11 Interventions

Patients receive dasatinib by mouth (PO) once a day (QD) and quercetin PO twice a day (BID) on days -7 and -6 and cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive CAR-T IV on day 0. Patients receive dasatinib PO QD and quercetin PO BID on days 28, 29, 58, 59, 88 and 89 in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET, tumor biopsy, bone marrow aspirate and biopsy and blood and urine sample collection throughout the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

CAR-T cell therapies targeting B-cell maturation antigen have shown significant effectiveness against multiple myeloma in early clinical trials, indicating a promising new treatment approach for this challenging cancer.

Toxicities observed in these CAR-T trials, such as cytokine release syndrome, are similar to those seen in CAR-T therapies for other blood cancers, highlighting the need for careful monitoring and management in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for multiple myeloma. Mikkilineni, L., Kochenderfer, JN.[2021]

The introduction of new therapies, including proteasome inhibitors, immunomodulators, and various immunotherapies like CAR T-cell treatments, has significantly improved the five-year survival rate for multiple myeloma to nearly 60%.

Despite these advancements, multiple myeloma remains incurable, as patients often become resistant to treatments and experience relapses, highlighting the need for ongoing research and development of new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. Abramson, HN.[2023]

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]

T-cell redirecting bispecific antibodies and CAR T cells are effective treatments for multiple myeloma but are associated with significant adverse events, including cytokine release syndrome and neurotoxicity.

The European Myeloma Network recommends specific management strategies for these adverse events, such as premedication, corticosteroids, and monitoring for symptoms, to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Ludwig, H., Terpos, E., van de Donk, N., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Synergistically Anti-Multiple Myeloma Effects: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib. [2022]

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

Chimeric antigen receptor T-cell therapies for multiple myeloma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Quercetin suppresses the proliferation of multiple myeloma cells by down-regulating IQ motif-containing GTPase activating protein 1 expression and extracellular signal-regulated kinase activation. [2019]

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

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. [2023]

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

Current developments in immunotherapy in the treatment of multiple myeloma. [2019]

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

CAR Ts and BiTEs Shine in Multiple Myeloma. [2021]