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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if standardizing the dose of CD3+ T cells, a type of immune cell, in bone marrow transplants can make the process smoother and more predictable. The focus is on helping patients who receive transplants from sibling donors by potentially reducing complications and improving outcomes. Participants should have a sibling donor with a perfect tissue match and meet specific health criteria, such as well-functioning organs and no uncontrolled infections. As an unphased trial, this study offers patients the opportunity to contribute to innovative research that could enhance transplant success and patient care.

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 prior data suggests that CD3+ T cell depletion is safe for bone marrow transplant recipients?

Research has shown that removing certain T-cells, called CD3+ T-cells, is generally safe for patients undergoing bone marrow transplants. This method reduces the risk of graft-versus-host disease (GVHD), where donor cells attack the patient's body. Studies suggest that patients receiving these specially treated transplants have similar survival rates to those who do not, indicating no harm to overall outcomes.

Additionally, removing CD3+ T-cells may lower the chances of disease recurrence, potentially improving long-term survival. Although there is a higher risk of the new cells not functioning properly, the overall safety remains favorable. This makes the removal of CD3+ T-cells a promising approach to enhancing the safety and reliability of bone marrow transplants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about CD3+ T-cell depletion because it offers a novel approach to bone marrow transplants. Unlike standard treatments, which often involve general immune suppression, this method specifically targets and removes certain T cells (CD3+ T cells) from the donor graft. By doing so, it aims to reduce the risk of graft-versus-host disease, a common and serious complication of bone marrow transplants. This targeted approach could lead to safer transplant procedures with fewer side effects, making it a potentially game-changing option for patients.

What evidence suggests that CD3+ T cell depletion might be an effective treatment for bone marrow transplant?

Research has shown that reducing CD3+ T cells can make bone marrow transplants safer and more effective. High levels of these T cells link to slower immune system recovery and a higher risk of graft-versus-host disease (GVHD), a serious complication. Lowering the number of CD3+ T cells may lead to better outcomes, such as improved engraftment (when the new cells settle in and grow) and fewer complications. Other studies suggest that fewer CD3+ T cells can improve survival rates after the transplant. These findings indicate that managing CD3+ T cell numbers could make transplants more predictable and safer for patients. Participants in this trial will receive CD3+ T-cell depletion to evaluate its effectiveness in improving transplant outcomes. ^{3 6 7 8 9}

Who Is on the Research Team?

Ayman Saad, MD

Principal Investigator

University of Alabama in Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7179384/

High proportions of CD3+ T cells in grafts delayed ... High levels of CD3 + T cells in the grafts were associated with delayed lymphocyte recovery and an increased risk of acute GVHD and decreased overall survival.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723000374

T Cell-Depleted Peripheral Blood versus Unmanipulated ... Our study shows that TCD PB can be considered a safe source for MSD-HSCT in patients with SAA, with potential advantages in engraftment and GVHD.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00589602

Study Details | NCT00589602 | T-Cell Depletion, Donor ... When stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and ...

4. astctjournal.org astctjournal.org/article/S1083-8791(18)30612-8/pdf

CD3+/CD19+ Depleted Matched and Mismatched ... Reports suggest that haploidentical HSCT using either post- transplant cyclophosphamide or ex vivo T cell depletion can be a highly effective strategy for ...

5. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.987220/full

T-cell depleted haploidentical hematopoietic ... Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation. Bone Marrow Transplant. (1997) 19(11):1069–77. doi: 10.1038/sj.bmt ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9990716/

The Impact of Graft CD3+ T-Cell Dose on the Outcome of T ... Our data suggest that high graft CD3 + T-cell dose is associated with lower risk of relapse, and might improve long-term survival.

7. nature.com nature.com/articles/bmt201722

Ex vivo T-cell depletion in allogeneic hematopoietic stem ... This showed TCD was associated with less risk of acute and chronic GvHD, higher risk of secondary graft failure and comparable survival outcome ...

8. astctjournal.org astctjournal.org/article/S1083-8791(18)30612-8/fulltext

CD3 + /CD19 + Depleted Matched and Mismatched ... Our data indicate that MUD and MMUD pTCD-PSCTs are safe and effective approaches that enable rapid engraftment and immune reconstitution, prevent severe GVHD, ...

9. ashpublications.org ashpublications.org/blood/article/98/12/3192/53143/The-history-and-future-of-T-cell-depletion-as

The history and future of T-cell depletion as graft-versus-host ... T-cell depletion (TCD) of the donor graft offers the potential for prevention of GVHD without the morbidity associated with immunosuppressive drugs.