CRISPR CAR-T Therapy for Multiple Myeloma

HC
Overseen ByHDFCCC Cancer Immunotherapy Program (CIP)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for people with multiple myeloma, a type of cancer affecting certain blood cells, which has either returned after treatment or hasn't responded to past treatments. The treatment uses modified immune cells called CAR-T cells (a type of immunotherapy) to target and destroy cancer cells. Researchers aim to determine the treatment's safety, potential side effects, and optimal dosage. Individuals whose multiple myeloma has returned or not responded after at least three treatments, and who have experienced recent disease progression, might be suitable for this trial. 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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that BCMA CAR-T cell therapy is generally safe, with manageable side effects. One study combined this therapy with pomalidomide, a drug for treating multiple myeloma, and found a low chance of disease recurrence, with manageable side effects. This indicates that the treatment is usually well-tolerated.

Although limited information exists about the CRISPR version of this therapy used in this trial, the Phase 1 trial status indicates that researchers are still gathering initial safety data. Phase 1 trials primarily ensure a new treatment's safety for people. While much remains to be learned about the treatment's safety, studies so far are promising and suggest it could benefit patients whose multiple myeloma has returned or is not responding to other treatments.12345

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy, stem cell transplants, or targeted therapies, CRISPR CAR-T therapy is unique because it uses gene editing to enhance the immune system. This treatment modifies a patient's own T cells to better recognize and attack cancer cells by targeting the BCMA protein found on multiple myeloma cells. Researchers are excited because this approach offers a personalized and potentially more effective way to combat the disease, with the possibility of long-lasting remission and fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatment could be effective for multiple myeloma?

Research has shown that BCMA CAR-T cell therapy holds promise for treating multiple myeloma, especially when other treatments have failed. In this trial, participants will receive different doses of BCMA CAR-T cells to determine the most effective and safe dose. One study found that these BCMA CAR-T cells effectively reduced cancer in the brain and spinal cord with few side effects. Patients receiving similar treatments have experienced long-term remission, with one-third remaining cancer-free for over five years without needing further treatment. BCMA-directed CAR-T therapy tends to work better when administered earlier in the treatment process. Additionally, CRISPR technology, used to modify these CAR-T cells, has successfully eliminated tumors in lab studies.13456

Who Is on the Research Team?

TG

Thomas G Martin, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for people with multiple myeloma that has returned or hasn't improved with treatment. Participants must have enough healthy blood cells and organ function, and can't have certain infections or immune conditions.

Inclusion Criteria

Voluntarily sign informed consent form
I had BCMA therapy but it's been 6 months since my last treatment.
Participants must have measurable disease, defined as Serum M-protein greater or equal to 0.5 grams per deciliter (g/dL), Urine M-protein greater or equal to 200 milligrams, over a 24-hour period (mg/24 h), Serum free light chain (FLC) assay: involved FLC level of ≥ 100 milligrams per liter (mg/L)
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Exclusion Criteria

I had a stem cell transplant using my own cells less than 12 weeks ago.
I haven't had cancer treatment recently.
Serologic status reflects active hepatitis B or C infection
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Leukapheresis and Lymphodepleting Chemotherapy

Participants undergo leukapheresis and receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide

1 week
3 visits (in-person)

CAR-T Cell Infusion

Participants receive a single infusion of BCMA CAR-T cells

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
Visits at 30, 60, 90 days, 6 and 12 months

Long-term Follow-up

Participants are followed up yearly for up to 15 years to monitor long-term outcomes

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

  • 1XX BCMA CAR-T cells

Trial Overview

The trial tests a new therapy where patients' T cells are modified using CRISPR to attack cancer cells. It includes collecting patient's T cells, modifying them in the lab, then infusing them back after chemotherapy.

How Is the Trial Designed?

3

Treatment groups

Experimental Treatment

Group I: Expansion: MTD of Anti-BCMA CAR-TExperimental Treatment8 Interventions
Group II: Dose Escalation: Planned Dose: 30 × 10^6 CAR + T cells/ infusionExperimental Treatment8 Interventions
Group III: Dose Escalation Starting Dose: 10 × 10^6 CAR + T cells/ infusionExperimental Treatment8 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Thomas Martin, MD

Lead Sponsor

Trials
4
Recruited
130+

Citations

CRISPR Delivered Anti-BCMA Car-T Therapy for Relapsed ...

Treatment with 1XX BCMA CAR-T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma ( ...

Long-Term (≥5-Year) Remission and Survival After ...

One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment.

Sequencing CAR T-Cell Therapy in the Evolving Myeloma ...

This interview discusses how BCMA-directed CAR T-cell therapy in multiple myeloma may be more effective when administered earlier in the ...

Clinical Outcomes of BCMA CAR-T Cells in a Multiple ...

This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events.

247 UCCT-BCMA-1: a first-in-human, non-viral CRISPR ...

In vivo, UCCT-BCMA-1 induced complete tumor clearance in two independent xenograft models using OPM2 multiple myeloma tumors, at doses ≥66k CAR+ ...

BCMA CAR-T therapy combined with pomalidomide is a safe ...

Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects.