What side effects are associated with this type of intervention?

Common treatments for multiple myeloma that are similar to WT1 sensitized T cells include various forms of immunotherapy and T-cell-based therapies. Known side effects of these treatments can include cytokine release syndrome (CRS), which manifests as fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. Other potential side effects are neurotoxicity, which can lead to confusion, difficulty speaking, and seizures, as well as increased risk of infections due to immunosuppression. Additionally, patients may experience fatigue, anemia, and gastrointestinal issues such as diarrhea and constipation.

What prior FDA approvals exist?

FDA-approved treatments for Multiple Myeloma include various immunotherapies and targeted therapies. Notable approvals include bortezomib, lenalidomide, and dexamethasone, which are often used in combination. Daratumumab, an anti-CD38 monoclonal antibody, has also been approved and is used in various combinations. Additionally, chimeric antigen receptor (CAR) T-cell therapies like idecabtagene vicleucel and ciltacabtagene autoleucel target BCMA on myeloma cells. These treatments share a similar approach to the WT1 Sensitized T Cells being studied, as they involve targeting specific proteins on myeloma cells to enhance immune response.

What other types of research exist?

Promising novel alternatives to WT1 sensitized T cells for multiple myeloma patients include: 1) CAR T-cell therapies such as idecabtagene vicleucel and ciltacabtagene autoleucel, which target BCMA on myeloma cells; 2) Bispecific antibodies like teclistamab, which also target BCMA; 3) Monoclonal antibodies such as daratumumab and isatuximab, which target CD38; and 4) Antibody-drug conjugates like belantamab mafodotin, which target BCMA. These therapies have shown significant efficacy in clinical trials and are expected to be important treatment options in 2024.

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CAR T-cell Therapy

WT1-specific T Cells for Multiple Myeloma

Phase 1

Waitlist Available

Led By Sergio Giralt, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must have multiple myeloma that has either relapsed or remains refractory following autologous stem cell transplantation and patients who have plasma cell leukemia at diagnosis

Patients with relapsed multiple myeloma following autologous stem cell transplantation who achieved < partial response following additional chemotherapy or who achieved < PR at 3 months following autologous stem cell transplantation and patients with plasma cell leukemia at diagnosis

Must not have

Patients who have had a previous malignancy that is not in remission

Female patients who are pregnant or breast-feeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety of special white blood cells from a donor that are trained to attack a protein made by multiple myeloma cancer cells. The goal is to see if these cells can effectively kill the cancer cells and understand their effects on patients.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to immune response such as inflammation, infection risk due to immunosuppression from chemotherapy drugs like busulfan, melphalan and fludarabine; complications from anti-thymocyte globulin (ATG), and issues arising from the stem cell transplant process.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My multiple myeloma or plasma cell leukemia didn't fully respond to initial treatments.

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I am between 21 and 73 years old.

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I am mostly able to care for myself and carry out daily activities.

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I have a donor who matches me completely in specific genetic markers.

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I have a donor ready to undergo procedures for my treatment.

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I don't have a perfect match donor, but I have one with only minor mismatches.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I am not pregnant or breastfeeding.

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I currently have an active infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

assess the toxicities

maximum tolerated dose (MTD)

Secondary study objectives

serologic response

survival

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Pts with Mutiple myelomaExperimental Treatment5 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

busulfan

1999

Completed Phase 3

~3630

melphalan

1994

Completed Phase 3

~3530

fludarabine

2012

Completed Phase 3

~6760

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Myeloma include proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and monoclonal antibodies (e.g., daratumumab). Proteasome inhibitors disrupt protein degradation, leading to cancer cell death. Immunomodulatory drugs enhance the immune system's ability to attack myeloma cells and inhibit their growth. Monoclonal antibodies target specific antigens on myeloma cells, marking them for destruction by the immune system. Treatments like WT1 Sensitized T Cells, which target the WT1 protein on myeloma cells, represent a novel approach by directly engaging the immune system to recognize and kill cancer cells. This is crucial for patients as it offers a targeted therapy that may improve outcomes and reduce side effects compared to conventional treatments.

Stem cell transplantation in multiple myeloma and other plasma cell disorders (report from an EBMT preceptorship meeting).How I treat high-risk myeloma.Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials.