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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new type of stem cell transplant for individuals with bone marrow failure syndromes. By using special stem cells from a closely matched donor, it explores treatments for conditions such as aplastic anemia and Fanconi anemia, among others that affect bone marrow. The trial focuses on those who have faced persistent issues like frequent blood transfusions or severe infections due to these syndromes. Participants will receive established chemotherapy or radiation before the stem cell transplant, which uses the CliniMACS system for TCR αβ depletion. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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 this stem cell transplant method is safe for bone marrow failure syndrome?

Research has shown that using specially prepared stem cells for transplants is generally well-tolerated. One study found that this method lowered the risk of graft-versus-host disease (GVHD), a common issue where donor immune cells attack the patient's body. This occurs because certain immune cells are removed from the donor's stem cells before administration to the patient.

Another study demonstrated that both adults and children handled this treatment well, showing promising results in treating bone marrow failure. Some side effects were reported, but they were mostly manageable and not severe.

Overall, the evidence suggests that this treatment approach is relatively safe for patients, though individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for bone marrow failure syndrome because they employ a unique technique known as TCRalpha/beta and B cell depletion. This approach targets specific immune cells to reduce the risk of transplant rejection and complications, which is a significant improvement over standard options like full-intensity chemotherapy or radiation. Unlike traditional treatments that can be harsh and indiscriminate, these tailored regimens use stem cells from unrelated or partially matched donors, broadening donor availability and potentially reducing the severity of side effects. This innovative method could offer a safer and more effective pathway for patients, particularly those with challenging conditions like Fanconi Anemia.

What evidence suggests that this trial's treatment could be effective for bone marrow failure syndrome?

Research has shown that specially treated stem cells can lower the risk of graft-versus-host disease (GVHD), a common issue in stem cell transplants. A review of several studies found positive results, particularly in children with blood-related conditions, by effectively removing unwanted donor T-cells. Another study confirmed the safety and practicality of this method, highlighting its potential benefits. In this trial, the CliniMACS system aids in the process by cleaning the stem cells before use, making transplants safer and more effective. Early findings suggest promise for people with bone marrow failure syndromes, and this trial will explore its effectiveness in different patient groups, including those with and without trilineage aplasia and those with Fanconi Anemia. ^{1 2 3 4 6}

Who Is on the Research Team?

Timothy S Olson, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04806347

Study Details | NCT04806347 | Alpha/Beta T-cell Depleted ... This single institution, phase I clinical trial will determine the safety and feasibility of employing T-cell receptor (TCR) αβ+ and CD19+ (Cluster of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6944939/

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy We report the results of the first ten TCRαβ+ and B cell depletion procedures for clinical use performed at our centre.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05968170

TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by efficiently removing donor T-cells from the graft prior to infusion by enriching ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0966327425000486

Comprehensive up-to-date analysis on TCRαβ/CD19 ... This meta-analysis assesses the efficacy of TCRαβ+/CD19+ depleted hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8702395/

Results of a multicenter phase I/II trial of TCRαβ and CD19- ... Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.

6. researchgate.net researchgate.net/publication/394862375_Long-term_outcomes_of_ab_T-cellCD19_B-cell-depleted_peripheral_blood_stem_cell_transplantation_from_unrelated_donors_in_pediatric_and_adolescent_patients_with_severe_aplastic_anemia_a_single-center_st

Long-term outcomes of αβ T-cell/CD19 B ... This study aimed to assess the prevalence of somatic mutations (SMs) in severe/very severe aplastic anemia (V/SAA) and transfusion-dependent ...