Stem Cell Transplantation for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Psychiatric illness, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-3 days

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test whether regulatory T-cell reduction is possible and safe in myeloma subjects undergoing autologous stem cell transplantation (ASCT).

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.

What data supports the effectiveness of the treatment for reducing regulatory T-cells in multiple myeloma patients?

Research suggests that higher levels of regulatory T-cells (a type of immune cell that can suppress the body's immune response) are linked to poorer outcomes in multiple myeloma patients. Reducing these cells might improve the effectiveness of treatments like donor lymphocyte infusions (DLIs) by enhancing the body's ability to fight the cancer. ^{1 2 3 4 5}

Is stem cell transplantation for multiple myeloma safe?

Stem cell transplantation for multiple myeloma has been generally well tolerated, but some patients experience side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and hematologic toxicities (blood-related side effects). While these treatments show promise, they can also have severe adverse events, so ongoing research is needed to better understand and manage these risks. ^{2 6 7 8 9}

How does the treatment of Regulatory T-cell reduction differ from other treatments for multiple myeloma?

Regulatory T-cell reduction in multiple myeloma is unique because it focuses on decreasing the number of regulatory T cells, which are known to suppress the immune response against cancer cells. This approach aims to enhance the body's natural ability to fight the cancer, unlike traditional treatments that primarily target the cancer cells directly. ^{1 2 3 4 5}

Research Team

Michael Bishop, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Depletion of T-cells before ASCT(Grp 3) Experimental Treatment 6 Interventions

Blood collected for an ASCT will be processed using a special cell sorting machine (CliniMACS device) to remove Treg cells before the stem cells are infused back into the body during stem cell transplant.

Group II: Depletion of T-cells after ASCT (Grp 2) Experimental Treatment 6 Interventions

Standard ASCT followed by treatment with basiliximab to remove certain immune cells (called regulatory T-cells or Tregs) from the blood

Group III: Standard ASCT (Grp 1) Active Control 5 Interventions

Standard autologous stem cell transplantation (ASCT)

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation generates T cell-dependent control of myeloma in mice. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Increased circulating CD4+FOXP3+ T cells associate with early relapse following autologous hematopoietic stem cell transplantation in multiple myeloma patients. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

The bone marrow of myeloma patients is steadily inhabited by a normal-sized pool of functional regulatory T cells irrespectiveof the disease status. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Increased Immune-Regulatory Receptor Expression on Effector T Cells as Early Indicators of Relapse Following Autologous Stem Cell Transplantation for Multiple Myeloma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell immunotherapy for multiple myeloma: A review of current data and potential clinical applications. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies. [2021]