ATLCAR.CD138 T Cells for Multiple Myeloma

Overseen By Kelly Hoye

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Immunomodulatory, Proteasome inhibitors

Must not be taking: Corticosteroids, Chemotherapy

Disqualifiers: Amyloidosis, POEMS syndrome, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve cancer treatment by combining two disease-fighting tools: antibodies and T cells, a type of immune cell. The focus is on developing a treatment for multiple myeloma, a type of blood cancer, by enhancing T cells with a special receptor that targets cancer cells. People with relapsed or hard-to-treat multiple myeloma who have undergone several rounds of chemotherapy might be a good fit for this trial. Participants will receive CAR138 T cells, which are modified to better recognize and attack cancer cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you must stop taking corticosteroids at least 48 hours before lymphodepleting chemotherapy and systemic chemotherapy at least 14 days before lymphodepletion. Radiation therapy should be stopped at least 7 days before lymphodepletion. Please consult with your doctor for specific guidance on other medications.

Will I have to stop taking my current medications?

The trial requires participants to stop taking systemic corticosteroids at doses of 10mg prednisone daily or higher at least 48 hours before starting lymphodepleting chemotherapy. Systemic chemotherapy must be stopped at least 14 days before lymphodepletion, and radiation therapy must be stopped at least 7 days before. Other medications are not specifically mentioned, so it's best to discuss with your doctor.

Is there any evidence suggesting that CAR138 T cells are likely to be safe for humans?

Research has shown that CAR138 T cells have been tested on both healthy individuals and those with multiple myeloma, a type of blood cancer. These studies indicate that the treatment is safe and generally well-tolerated. In one study, patients who received CAR138 T cells demonstrated a strong response against multiple myeloma. Importantly, the treatment did not cause severe side effects, suggesting it is a practical option for patients. While more research is needed, these findings suggest CAR138 T cells could be a promising and safe treatment choice. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for multiple myeloma?

Unlike many current treatments for multiple myeloma, which often involve chemotherapy or stem cell transplantation, CAR138 T cells offer a cutting-edge approach by using the body's own immune cells, genetically engineered to target CD138, a protein commonly found on myeloma cells. This personalized therapy aims to enhance the immune system’s ability to recognize and destroy cancer cells more effectively. Researchers are excited about CAR138 T cells because they represent a new mechanism of action with the potential for improved specificity and reduced side effects compared to traditional therapies.

What evidence suggests that CAR138 T cells might be an effective treatment for multiple myeloma?

Research has shown that CAR T-cell therapies, such as CAR138 T Cells, effectively treat certain blood cancers. Studies have found that these therapies can lead to impressive results, with many patients experiencing no worsening of their disease for nearly three years. In this trial, CAR138 T Cells specifically target and destroy multiple myeloma cells by recognizing a marker called CD138 on the cancer cells. While anti-CD138 antibodies alone haven't been strong enough to cure most patients, combining them with T cells might enhance their effectiveness. Early studies suggest that CD138-targeted CAR T-cells are safe and show potential to fight tumors, making them a promising option for further research. ^{1 2 5 6 7}

Who Is on the Research Team?

Sascha Tuchman, MD, MHS

Principal Investigator

Assoc. Professor, Dir. of the UNC MM and Amyloidosis Program, UNC LCCC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory multiple myeloma, who've had at least three prior chemotherapy treatments and are not eligible for or have declined a stem-cell transplant. Participants need to be in stable condition without infections, serious heart issues, or other cancers. They must agree to use contraception if necessary and comply with study procedures.

Inclusion Criteria

Not pregnant or breastfeeding

Willing and able to comply with study procedures

No medical condition making the protocol unreasonably hazardous

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Up to 300 mL total of peripheral blood will be obtained from subjects for cell procurement. In subjects with a low CD3 count, a leukopheresis may be performed.

1-2 weeks

Lymphodepletion

Lymphodepletion regimen consisting of Cyclophosphamide and Fludarabine administered daily over 3 consecutive days.

1 week

CAR138 T-cell Administration

Autologous CAR138 T-cells administered 2-14 days following lymphodepletion via intravenous injection.

1-2 weeks

Safety Monitoring

Subjects monitored for dose limiting toxicities and safety evaluation for at least 2 weeks following CAR138 T-cell infusion.

2 weeks

Follow-up

Subjects are monitored for safety and effectiveness after treatment, including evaluation of progression free survival, overall survival, and replication-competent retrovirus monitoring.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CAR138 T Cells

Trial Overview The trial is testing CAR138 T cells, which are the patient's own immune cells modified to target cancer cells more effectively. These special T cells carry a part of an antibody that recognizes and attaches to multiple myeloma cells, potentially enhancing the body's ability to fight this type of cancer.

How Is the Trial Designed?

Group I: CAR138 T cells Experimental Treatment 1 Intervention

The first 3 subjects enrolled in the study will receive 5x10\^6 CAR138 T-cells/m\^2 via infusion. The number of cells for the infusion will be increased to 1x10\^7 CAR138 T-cells/m\^2 and then, 2.5x10\^7 CAR138 T-cells/m\^2, 5x10\^7 CAR138 T-cells/m\^2, 1x10\^8 CAR138 T-cells/m\^2 and 2x10\^8 CAR138 T-cells/m\^2 in subsequent cohorts of 3 subjects provided no dose limiting toxicities (DLTs) are observed within 4 weeks of the cell infusion. Cohort enrollment will be staggered, requiring each subject to complete at least 2 weeks of safety monitoring following CAR138 T-cell infusion at the designated dose level for the cohort before another subject is allowed to enroll in the cohort.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Collaborator

Trials

5

Recruited

150+

Published Research Related to This Trial

The study developed dual-split CAR T cells targeting CD38 and CD138, which effectively killed multiple myeloma cells while sparing healthy cells, demonstrating a promising approach for enhancing specificity in CAR T-cell therapy.

The optimal combination of a low-affinity CD138sCAR and a high-affinity CD38cCAR showed effective anti-multiple myeloma activity in vivo, even against cells from patients previously treated with daratumumab, indicating potential for broader application in resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138. van der Schans, JJ., Wang, Z., van Arkel, J., et al.[2023]

The dual-CAR T-cell therapy targeting CD138 and CD38 showed a significant anti-multiple myeloma response, resulting in a median survival of 97 days in treated mice compared to 31 days in the control group, indicating its potential efficacy.

This approach demonstrated increased specificity for cancer cells coexpressing both antigens while minimizing off-target effects on healthy tissues, suggesting a safer treatment option for multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity. Globerson Levin, A., Rawet Slobodkin, M., Waks, T., et al.[2021]

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]

Chimeric antigen receptor (CAR) T cells targeting CD138 have shown the ability to effectively eliminate both tumor cell lines and primary myeloma cells in laboratory and animal studies, indicating their potential as a treatment for multiple myeloma.

Preclinical studies demonstrated that these CD138-specific CAR T cells did not cause damage to normal epithelial or endothelial cells, suggesting a favorable safety profile for this therapy in patients with relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma. Sun, C., Mahendravada, A., Ballard, B., et al.[2020]

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 phase 1 study involving 57 patients with relapsed/refractory multiple myeloma, LCAR-B38M CAR T cell therapy showed an impressive overall response rate of 88%, with 68% of patients achieving a complete response.

While the therapy had a manageable safety profile, with common adverse events including leukopenia and cytokine release syndrome, it demonstrated durable responses with a median progression-free survival of 15 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. Zhao, WH., Liu, J., Wang, BY., et al.[2020]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

Multiple myeloma remains an incurable disease, and patients often experience relapses after standard treatments, leading to a poor prognosis.

Chimeric antigen receptor (CAR) T-cell therapy shows promise in improving outcomes for relapsed multiple myeloma, although it is not yet approved for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far-And the Road Ahead. Cowan, AJ., Tuazon, SA., Portuguese, AJ., et al.[2022]

In a study of 22 patients with relapsed or refractory multiple myeloma, a combination of anti-BCMA and anti-CD38 CAR-T cell therapy showed a high overall response rate of 90.9%, with over half achieving a complete response.

While the treatment demonstrated significant efficacy, it also resulted in cytokine release syndrome in 72.7% of patients, indicating the need for careful monitoring of side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. Zhang, H., Liu, M., Xiao, X., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03672318

Study of ATLCAR.CD138 Cells for Relapsed/Refractory ... Anti-CD138 antibodies have been used to treat people with multiple myeloma, but have not been strong enough to cure most subjects. For this study, the anti- ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352177515000023

CD138-directed adoptive immunotherapy of chimeric ... This study suggests that the treatment of CART-138 is safe, feasible, and tolerable and has potential antitumor activity in vivo, warranting further research.

3. ashpublications.org ashpublications.org/hematology/article/2023/1/340/506389/Current-use-of-CAR-T-cells-to-treat-multiple

Current use of CAR T cells to treat multiple myeloma CAR T-cell therapies currently approved by the US Food and Drug Administration (FDA) have dramatically improved clinical outcomes for patients with heavily ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6481321/

Safety and efficacy of targeting CD138 with a chimeric antigen ... After unprecedented successes in B-cell malignancies, chimeric antigen receptor T cells have recently been investigated for the treatment of multiple myeloma.

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

CAR-T cell therapy in Multiple Myeloma: current status and ... Updated results after 33 months follow-up reported an impressive median PFS of 34.9 months with an estimated 63% OS at 36 months [28]. In cohort ...

6. withpower.com withpower.com/trial/phase-1-immune-system-diseases-2019-3efde

ATLCAR.CD138 T Cells for Multiple Myeloma The dual-CAR T-cell therapy targeting CD138 and CD38 showed a significant anti-multiple myeloma response, resulting in a median survival of 97 days in treated ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03672318/

Clinical Trial: NCT03672318 This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is ...