WT1-specific T Cells for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Active infection, HIV, 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 tests a new approach for treating multiple myeloma, a type of blood cancer. Researchers aim to determine if specially prepared immune cells, called WT1-specific T cells, can target and destroy cancer cells. These donor-derived T cells are designed to recognize a protein produced by the cancer cells. The trial will assess the safety and effectiveness of this treatment. It may suit those whose multiple myeloma has returned or not responded to previous treatments and who have a matched or compatible donor available.

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 new therapy.

Do I need to stop 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.

Is there any evidence suggesting that WT1-specific donor-derived T cells are likely to be safe for humans?

Research has shown that WT1-specific T-cell therapy, like the one tested in this trial, is generally safe. Previous studies found that these special T cells remain in the body and effectively target cancer cells. In trials with similar treatments for conditions like acute leukemia, patients responded well, with some living for more than a year.

However, the level of WT1 protein in multiple myeloma cells is lower than in other cancers, which might affect the efficacy of these T cells. The studies did not report major safety issues, but since this is an early-phase trial, the primary goal is to assess safety. Researchers are closely monitoring for any side effects and how well patients tolerate the treatment. Participants in this trial will provide crucial information on the safety and effectiveness of this approach for multiple myeloma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about WT1-specific T cells for multiple myeloma because these cells offer a targeted approach, unlike traditional treatments such as chemotherapy and stem cell transplants. The WT1-specific T cells are designed to recognize and attack cancer cells that express the WT1 protein, which could reduce the risk of relapse after a transplant. This precise targeting might also lead to fewer side effects compared to conventional therapies. By harnessing the body's own immune system to fight the cancer, this approach represents a promising advancement in treating multiple myeloma.

What evidence suggests that WT1-specific T cells might be an effective treatment for multiple myeloma?

Studies have shown that special immune cells, called WT1-specific T cells, can help fight multiple myeloma, a type of blood cancer. These cells target a protein called WT1, found on myeloma cells. When the T cells recognize the WT1 protein, they attack and destroy the cancer cells. Research indicates that patients with strong responses from these WT1-specific T cells tend to have better outcomes. One study found that most patients with ongoing WT1-specific T cell activity lived for more than a year. In this trial, participants will receive WT1-specific donor-derived T cells following a preparative regimen and stem cell transplant. These findings suggest that using WT1-specific T cells from donors might effectively treat multiple myeloma by slowing the growth of cancer cells. ^{2 3 4 5 6}

Who Is on the Research Team?

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 21-73 with relapsed multiple myeloma post-autologous stem cell transplant or plasma cell leukemia at diagnosis. Participants need a matched donor for T-cell depleted stem cell transplant, good organ function, and a performance status >70%. Pregnant women, those with active infections or other malignancies not in remission, HIV/HTLV-positive individuals, and those allergic to mouse proteins or chicken eggs are excluded.

Inclusion Criteria

My heart, liver, kidneys, and lungs are all functioning well.

My gender or ethnic background does not limit my participation.

My multiple myeloma has returned or didn't respond after a stem cell transplant.

Exclusion Criteria

You have tested positive for HIV or HTLV.

I have had cancer before that is not currently in remission.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen and Transplantation

Patients undergo a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), followed by a T cell depleted stem cell transplant from a histocompatible donor.

3-4 weeks

WT1-specific T Cell Infusion

Administration of WT1-specific cytotoxic T cells post transplantation to induce complete remissions and decrease relapse rate.

3 weeks

Follow-up

Participants are monitored for safety, effectiveness, and serologic responses after treatment, including toxicities and survival.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• WT1-specific Donor-derived T Cells

Trial Overview The study tests the safety of different doses of WT1-specific donor-derived T cells after a T-cell depleted allogeneic hematopoietic stem cell transplantation. These lab-grown white cells target the Wilms' tumor protein (WT1) expressed by myeloma cells to see if they can effectively kill them.

How Is the Trial Designed?

Group I: Pts with Mutiple myeloma Experimental Treatment 5 Interventions

Patients will undergo a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor. Hematopoietic stem cell donors for this trial will include individuals who are 10/10 HLA matched or one antigen or allele mismatched at the HLA-A, B, C, DRB1 or DQB1 locus, as defined by high resolution methods .Donors who are 8/10 HLA matched with an antigen or allele mismatched at HLA-DQB1 and at one other locus will also be eligible for the trial. The administration of WT1-specific cytotoxic T cells (WT1 CTLs) post transplantation is integrated to induce complete remissions in patients with residual disease and to decrease the rate of relapse following the allogeneic transplant.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3952597/

WT1-specific T-cell responses in high-risk multiple ... Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood. 1997;90(10):4206–4211. [PubMed] ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3782135/

The emergence of WT1-specific T-cell responses following ... The development of T-cell responses specific for myeloma-associated antigens correlates with improved clinical outcomes in multiple myeloma patients ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120327488

Safety and persistence of WT1-specific T-cell receptor ... Four of 5 patients who had persistent T cells at the end of the study survived more than 12 months. These results suggest WT1-specific TCR-T ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/10/21/7402/183703/Myeloma-Cells-Are-Highly-Sensitive-to-the-Granule

Myeloma Cells Are Highly Sensitive to the Granule Exocytosis ... Results: The expression levels of WT1 mRNA in myeloma and lymphoma cells were significantly lower than that in acute leukemia cells. Although the WT1 expression ...

5. jitc.bmj.com jitc.bmj.com/content/10/6/e004409

WT1-specific TCRs directed against newly identified ... Notably, T-cell clones for WT1 peptides previously used in clinical trials lacked reactivity against tumor cells, suggesting limited processing ...

6. ashpublications.org ashpublications.org/blood/article/130/18/1985/36534/Safety-and-persistence-of-WT1-specific-T-cell

Safety and persistence of WT1-specific T-cell receptor gene ... WT1-specific TCR-redirected T-cell therapy for AML and MDS is safe, and the T cells persisted in vivo and trafficked to bone marrow.