Stem Cell Transplantation for Multiple Myeloma

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 aims to determine if reducing certain immune cells (regulatory T-cells) is possible and safe for people with multiple myeloma during a stem cell transplant. Multiple myeloma is a type of blood cancer, and the study will test three approaches: standard stem cell transplant, removing these immune cells after the transplant, and removing them before. People diagnosed with symptomatic multiple myeloma and who are candidates for stem cell transplants may be eligible.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Do I need to stop taking my current medications for the trial?

The trial requires that you do not use systemic immunosuppressive medications, including corticosteroids and certain other drugs. If you are taking these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that using basiliximab to lower the number of regulatory T-cells (a type of immune cell) after stem cell transplants was very safe. Patients experienced fewer infections, particularly viral ones, which is crucial since infections are a common concern after these procedures.

Research shows that removing these cells before the transplant is feasible and significantly delays the return of T-cells after the procedure. This delay helps control the immune response, which can benefit patients with multiple myeloma.

Both methods of reducing T-cells remain in early testing stages, with a primary focus on safety. While these studies suggest safety, researchers are closely monitoring the treatments for any side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they explore a novel approach to managing the disease. Unlike the standard of care, which typically includes chemotherapy, radiation, and standard autologous stem cell transplantation (ASCT), these investigational treatments focus on manipulating the immune system by reducing regulatory T-cells (Tregs). By using basiliximab to deplete Tregs after ASCT or a special cell sorting machine to remove Tregs before ASCT, these treatments aim to enhance the body's ability to fight cancer by potentially allowing a more robust immune response. This innovative strategy could offer a new way to improve outcomes for multiple myeloma patients beyond what current therapies can achieve.

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

Research shows that certain cells in the immune system, called regulatory T-cells (Tregs), play an important role in multiple myeloma, a type of blood cancer. These Tregs can weaken the body's ability to fight myeloma cells, potentially allowing the cancer to grow. Studies have found that lowering the number of Tregs can boost the immune system's ability to combat myeloma. In this trial, participants will be assigned to different treatment arms to explore this approach. One group will undergo standard autologous stem cell transplantation (ASCT), while another group will receive treatment to deplete Tregs after ASCT using basiliximab. A third group will have Tregs removed from their blood before ASCT using a special cell sorting machine. Targeting Tregs could be a promising way to improve treatment results for people with multiple myeloma.678910

Who Is on the Research Team?

MB

Michael Bishop, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults aged 21-70 with symptomatic multiple myeloma who are candidates for stem cell transplantation. They must have a life expectancy over 12 weeks, be HIV negative, not have active hepatitis B or C, and no major organ issues. Pregnant women, those on immunosuppressants or with autoimmune diseases cannot participate.

Inclusion Criteria

I am between 21 and 70 years old.
My doctor has approved me for a stem cell transplant.
I can do most of my daily activities on my own.
See 7 more

Exclusion Criteria

I have an active autoimmune disease like rheumatoid arthritis or lupus.
I am not taking any immune-suppressing drugs like steroids or tacrolimus.
I am not pregnant or nursing. If of child-bearing age, I have been tested for pregnancy.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo autologous stem cell transplantation (ASCT) with or without regulatory T-cell depletion

1-3 days
In-patient procedure

Recovery and Monitoring

Monitoring of regulatory T cell depletion and recovery, and incidence of autologous graft-versus-host disease

180 days
Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

What Are the Treatments Tested in This Trial?

Interventions

  • Regulatory T-cell reduction
Trial Overview The study tests if it's safe to reduce regulatory T-cells in myeloma patients during autologous stem cell transplantation using drugs like G-CSF, Basiliximab and Melphalan along with techniques such as Apheresis and CliniMACS CD25 sorting.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Depletion of T-cells before ASCT(Grp 3)Experimental Treatment6 Interventions
Group II: Depletion of T-cells after ASCT (Grp 2)Experimental Treatment6 Interventions
Group III: Standard ASCT (Grp 1)Active Control5 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials
1,086
Recruited
844,000+

Published Research Related to This Trial

CAR T cell therapies targeting BCMA have shown promising results in early clinical trials for treating multiple myeloma, indicating potential for long-lasting remissions.
However, these therapies are associated with significant toxicities, including cytokine release syndrome and neurotoxicity, highlighting the need for ongoing research to improve their safety and effectiveness.
Chimeric antigen receptor T cell immunotherapy for multiple myeloma: A review of current data and potential clinical applications.Susanibar Adaniya, SP., Cohen, AD., Garfall, AL.[2020]
In a study involving 15 multiple myeloma patients undergoing autologous stem cell transplantation (ASCT), two methods of depleting regulatory T (Treg) cells were tested, showing that both in vivo (IVTRD) and ex vivo (EVTRD) methods significantly reduced Treg levels post-transplant.
The ex vivo method (EVTRD) effectively removed 90% of Treg cells from the stem cell grafts, and both methods delayed Treg recovery, which could enhance the effectiveness of post-transplant immunotherapies and improve patient outcomes.
Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study.Derman, BA., Zha, Y., Zimmerman, TM., et al.[2021]
Monoclonal antibodies like elotuzumab and daratumumab have advanced the treatment of multiple myeloma, while CAR T cell therapy is emerging as a promising option for patients with relapsed/refractory multiple myeloma, offering hope for those with limited treatment options.
Despite its potential efficacy, CAR T cell therapy can lead to severe adverse events and toxic deaths, highlighting the need for better understanding and management strategies for these toxicities in clinical practice.
Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.Zhou, X., Rasche, L., Kortüm, KM., et al.[2021]

Citations

Transient regulatory T-cell targeting triggers immune ...Continuous advances in multiple myeloma (MM) therapy have improved the 5-year survival from 25% to over 50% over the last four decades [1].
What happens to regulatory T cells in multiple myeloma - PMCRegulatory T cells have been shown to have massive infiltration of a variety of solid tumors in humans and mice as well as increased cellular ...
Regulatory T cells suppress myeloma-specific immunity ...In this study, we demonstrated that Treg depletion during SCM dramatically enhances antimyeloma immunity, resulting in potent myeloma control ...
T Cells Dysfunction in Multiple Myeloma | ITTStudies have demonstrated that the Treg/Th17 ratio is elevated in MM patients and lower in long-term survivors. An increase of the Treg/Th17 ...
Marrow-Infiltrating Regulatory T Cells Correlate with the ...We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation ...
T-Cell Redirecting Therapies in Multiple MyelomaThis review consolidates current evidence on these emerging toxicities, with the aim of informing clinical practice and supporting decision-making.
Donor antigen-specific regulatory T cell administration to ...Aggregate results of the consortium trial similarly revealed a high degree of safety and reduced incidence of infectious complications, particularly viral ...
Rapamycin-resistant polyclonal Th1/Tc1 cell therapy ...Results From December 2020 to December 2022, 14 patients with RRMM received a median of three RAPA-201 infusions (median dose, 80×106 cells).
Manipulating T cell-mediated pathology: Targets and ...This review discusses how the properties of Abs can be exploited for manipulating pathological T cell responses in the clinic.
Effect of Thymoglobulin Versus Basiliximab on Regulatory ...This study aims to study the effects that two standard-of-care immunosuppression induction regimens have on regulatory T cells (Treg) in live donor renal ...
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