Standardized T Cell Dose for Bone Marrow Transplant

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Donna Salzman

Disqualifiers: HIV, Prior transplants, Uncontrolled infections, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Stem cells collected from sibling donors for allogenic transplants contain various types of cells. The predominant immune cells are called CD3+ T cells. The amount of these T cells vary vastly from donor to donor. This study is to determine if standardizing the CD3+ T cell dose will benefit the recipient (patient). As well as to help discover if dose standardization causes less variation in outcomes between patients and to make transplantation more predictable and complications easier to manage.

Will I have to stop taking my current medications?

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.

What data supports the effectiveness of the treatment CD3+ T cell depletion for bone marrow transplant?

Research shows that T cell depletion can effectively reduce the risk of graft-versus-host disease (a condition where the donor's immune cells attack the recipient's body) in bone marrow transplants. However, it may also increase the chances of graft failure and leukemia relapse, indicating a need for careful balance in treatment strategies. ^{1 2 3 4 5}

Is the standardized T cell dose for bone marrow transplant generally safe in humans?

T cell depletion in bone marrow transplants can reduce the risk of graft-versus-host disease (a condition where the donor cells attack the recipient's body) but may increase the risk of graft failure and leukemia relapse. Some studies suggest that using additional medications like cyclosporine and methotrexate can help manage these risks, indicating that the procedure can be safe with careful management. ^{1 2 3 6 7}

How does the CD3+ T cell depletion treatment differ from other treatments for bone marrow transplant?

The CD3+ T cell depletion treatment is unique because it involves reducing the number of T cells (a type of immune cell) in the donor bone marrow to prevent graft-versus-host disease, a common complication in bone marrow transplants. This approach is different from other treatments as it focuses on adjusting the T cell dose to balance reducing the risk of this disease while maintaining immune recovery. ^{1 3 5 8 9}

Research Team

Ayman Saad, MD

Principal Investigator

University of Alabama in Birmingham

Eligibility Criteria

This trial is for adults over 19 who need a bone marrow transplant and have a perfectly matched sibling donor. They should fit specific health criteria, like good heart, kidney, lung function, and overall strength (Karnofsky ≥ 70%). People with previous transplants, certain high-risk disease features or uncontrolled infections can't join.

Inclusion Criteria

My organs are functioning well, tested within the last 28 days.

My heart's pumping ability is normal or above normal.

My kidney function, measured by creatinine clearance, is good.

Exclusion Criteria

I have had a stem cell transplant before.

My leukemia or lymphoma is not responding well to treatment.

I do not have any uncontrolled infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants undergo a preparative regimen prior to receiving the stem cell transplant

1-2 weeks

Transplantation

Participants receive a peripheral blood stem cell product engineered to deliver a standardized dose of CD3+ T cells

1 day

Follow-up

Participants are monitored for engraftment, immune reconstitution, and complications such as GVHD

12 weeks

Treatment Details

Interventions

• CD3+ T cell depletion

Trial Overview The study tests if standardizing the dose of immune cells (CD3+ T cells) in stem cell transplants from siblings makes treatment outcomes more predictable and manageable. It aims to see if this approach benefits patients by reducing complications.

Participant Groups

Group I: CD3+ T-cell depletion Experimental Treatment 1 Intervention

CD3+ T-cell depletion

Who Is Running the Clinical Trial?

Donna Salzman

Lead Sponsor

Trials

1

Recruited

20+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Miltenyi Biotec, Inc.

Industry Sponsor

Trials

11

Recruited

280+

Findings from Research

T-cell depletion in HLA-identical sibling bone marrow transplants significantly reduces the incidence of acute and chronic graft-versus-host disease (GVHD), but it also increases the risk of graft failure and leukemia relapse, particularly in patients with acute leukemia or chronic myelogenous leukemia.

Among T-cell-depleted transplant recipients, certain factors like higher radiation doses and specific post-transplant immune suppression strategies were associated with fewer treatment failures, suggesting that careful management of these variables could improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell depletion of HLA-identical transplants in leukemia. Marmont, AM., Horowitz, MM., Gale, RP., et al.[2023]

T-cell depletion of donor bone marrow is the most effective method reported for preventing graft-versus-host disease (GVHD) and reducing mortality, particularly benefiting children with immunodeficiency.

However, applying T-cell depletion in bone marrow transplants for leukemia has been challenging, leading to higher rates of engraftment failure and leukemia relapse compared to unmodified transplants, indicating a need for improved preparative regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell depletion for bone marrow transplantation: effects on graft rejection, graft-versus-host disease, graft-versus-leukemia, and survival. Champlin, RE.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Laboratory control in predicting clinical efficacy of T cell-depletion procedures used for prevention of graft-versus-host disease: importance of limiting dilution analysis. [2015]

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

T-cell depletion of HLA-identical transplants in leukemia. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy. [2017]

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

T-cell depletion for bone marrow transplantation: effects on graft rejection, graft-versus-host disease, graft-versus-leukemia, and survival. [2019]

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

The combined use of soybean agglutinin and immunomagnetic beads for T lymphocyte subset depletion of bone marrow allografts: a laboratory analysis. [2023]

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

Characteristics of CliniMACS® System CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

A new marrow T cell depletion method using anti-CD6 monoclonal antibody-conjugated magnetic beads and its clinical application for prevention of acute graft-vs.-host disease in allogeneic bone marrow transplantation: results of a phase I-II trial. [2013]

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

From 'megadose' haploidentical hematopoietic stem cell transplants in acute leukemia to tolerance induction in organ transplantation. [2007]

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

[Quantitative determination of human bone marrow T cells following in vitro depletion by Campath-1 monoclonal antibody]. [2014]