Stem Cell Transplant for Bone Marrow Failure Syndrome

Overseen By Megan Atkinson

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Myelodysplastic syndrome, No suitable donor, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.

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 CliniMACS, TCR αβ depletion, αβ T-cell depletion for bone marrow failure syndrome?

The CliniMACS system, used for T-cell depletion, has shown effectiveness in improving the purity and recovery of stem cells in transplants, which is important for successful outcomes. Additionally, T-cell depletion has been associated with reduced risk of graft-versus-host disease, a common complication in transplants. ^{1 2 3 4 5}

Is the stem cell transplant using CliniMACS and TCR αβ depletion safe for humans?

The CliniMACS system, used for TCR αβ and CD19 cell depletion, has been applied in various stem cell transplants and is generally considered safe, though it requires careful handling and has been associated with some risks like increased chances of graft failure and leukemia relapse in certain cases. ^{1 3 4 5 6}

How is the CliniMACs treatment different from other treatments for bone marrow failure syndrome?

The CliniMACs treatment is unique because it uses a process called TCR αβ and B cell depletion to prepare stem cell transplants, which helps reduce the risk of complications like graft-versus-host disease (GVHD) by removing specific immune cells from the donor graft. This method is particularly beneficial for patients receiving stem cell transplants from partially matched donors, as it allows for a safer and more effective transplant process. ^{1 3 4 5 7}

Research Team

Timothy S Olson, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for patients with various bone marrow failure syndromes who have suitable organ function and no active infections. It's open to those able to consent or minors with guardian consent, including specific conditions like Fanconi anemia, severe aplastic anemia, and others linked to bone marrow failure. Pregnant women or those without a closely matched donor are excluded.

Inclusion Criteria

I have a genetic condition that mainly affects one type of blood cell.

I have been diagnosed with severe or very severe aplastic anemia.

I have a condition that causes my red blood cells to break down at night.

Exclusion Criteria

My condition does not match the specific disease, organ, or infection criteria.

Pregnant females. All females of childbearing potential must have negative pregnancy test

I don't have a closely matched donor for a transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive disease-specific chemotherapy and/or radiation-based conditioning regimens

1-2 weeks

Transplantation

Hematopoietic stem cell transplantation using TCR alpha/beta and B cell depleted peripheral blood stem cells

1 week

Follow-up

Participants are monitored for engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and survival

1 year

Treatment Details

Interventions

• CliniMACs

Trial Overview The study tests the use of TCR alpha/beta+ T cell-depleted peripheral blood stem cells from unrelated donors or partially matched relatives in treating acquired and inherited bone marrow failures. This single-arm pilot study aims to assess the safety and effectiveness of this transplant method.

Participant Groups

Group I: TCRalpha/beta Tcell Depletion for BMF with trilineage aplasia Experimental Treatment 1 Intervention

Patients with acquired or inherited bone marrow failure (iBMF) with trilineage aplasia excluding Fanconi Anemia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

Group II: TCRalpha/beta Tcell Depletion for BMF w/o trilineage aplasia Experimental Treatment 1 Intervention

Patients with acquired or inherited bone marrow failure (iBMF) without trilineage aplasia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

Group III: TCRalpha/beta Tcell Depletion for BMF w/ Fanconi Anemia Experimental Treatment 1 Intervention

Patients with acquired or inherited bone marrow failure (iBMF) with Fanconi Anemia and related DNA Repair Disorders will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

CliniMACs is already approved in European Union, United States for the following indications:

Approved in European Union as CliniMACS for:

• Hematological malignancies
• Bone marrow failure syndromes

Approved in United States as CliniMACS for:

• Acquired and inherited bone marrow failure syndromes
• Leukemia
• Myelodysplastic syndrome

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Findings from Research

A new automated process using the CliniMACS Prodigy successfully depletes alloreactive T cells from hematopoietic stem cell grafts, achieving a high depletion efficiency of 4 log for both CD45RA+ and TCRαβ/CD19+ cells with minimal manual intervention.

The resulting products maintain a high viability of over 90% for stem cells and retain important immune cells like TCRγδ+ and NK cells, which are crucial for immunological surveillance, making them suitable for haplo-identical hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product. Wiercinska, E., Quade-Lyssy, P., Hümmer, C., et al.[2023]

The CliniMACS Prodigy system allows for a complete recovery (100%) of CD34+ cells after selection, which is crucial for hematology patients undergoing treatment.

This optimization in cell recovery can significantly enhance the effectiveness of therapies that rely on CD34+ cells, improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. Pello, OM., Lanzarot, D., Colorado, M., et al.[2020]

The study evaluated two methods for T cell depletion in peripheral blood stem cell grafts, finding that the CliniMACS system provided higher purity (94.87%) and recovery (58%) of CD34+ cells compared to the CellPro system, which had a purity of 85.6% and recovery of 24.8%.

Both methods are deemed suitable for preparing stem cell grafts for mismatched transplants in patients with severe hematological disorders and for autologous transplants in autoimmune diseases, but the CliniMACS system is preferred due to its superior efficiency in T cell removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two different methods for CD34+ selection and T cell depletion in peripheral blood stem cell grafts--our experiences with CellPro, E rosetting and CliniMACS technique. Poloucková, A., Vodvárková, A., Kobylka, P., et al.[2006]

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]

The CliniMACS Prodigy® system successfully performed TCRαβ+ T cell and B cell depletion in ten haploidentical stem cell transplants, achieving a median log reduction of TCRαβ+ cells of -4.21, indicating effective cell removal.

The procedure demonstrated reliability and ease of use, with a median CD34 recovery of 83%, although B cell depletion was slightly less efficient with a median log reduction of -3.72.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy: Results of 10 Graft-Processing Procedures from Haploidentical Donors. Haastrup, E., Ifversen, MRS., Heilmann, C., et al.[2022]

The CliniMACS device effectively depleted TCRαβ(+) T cells by an average of 4.7 logs and B cells by 4.1 logs, achieving very low residual levels of these cells in apheresis products, which is crucial for certain therapeutic applications.

The recovery rates for key cell types post-separation were high, with 73% for CD34(+) stem cells and 80% for natural killer cells, while maintaining a cell viability of 98%, indicating that the CliniMACS system is both effective and safe for preparing cell products for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device. Schumm, M., Lang, P., Bethge, W., et al.[2020]

The study successfully demonstrated the simultaneous depletion of T and B cells from mobilized peripheral blood stem cells (PBSCs) using the CliniMACS device, achieving a T cell depletion efficiency of 99.98% and B cell depletion of over 99.99%.

Importantly, the depletion process did not adversely affect the function of the remaining hematopoietic stem cells, maintaining a high recovery rate of CD34(+) cells and NK cells, which is crucial for the success of haploidentical stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[An effective method for T-cell and B-cell simultaneous depletion in vitro from mobilized peripheral blood stem/progenitor cell graft for haploidentical transplantation]. Xiao, J., Li, HH., Jin, XS., et al.[2017]

References

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

Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. [2020]

3. Slovakia pubmed.ncbi.nlm.nih.gov

Comparison of two different methods for CD34+ selection and T cell depletion in peripheral blood stem cell grafts--our experiences with CellPro, E rosetting and CliniMACS technique. [2006]

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

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

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

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy: Results of 10 Graft-Processing Procedures from Haploidentical Donors. [2022]

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

Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device. [2020]

7. China pubmed.ncbi.nlm.nih.gov

[An effective method for T-cell and B-cell simultaneous depletion in vitro from mobilized peripheral blood stem/progenitor cell graft for haploidentical transplantation]. [2017]