Stem Cell Transplant for Bone Marrow Failure Syndrome

(ExpMACs Trial)

Overseen By Megan Atkinson

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Infections, HLA matched sibling, pregnancy

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

Duration: 4-6 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special type of stem cell transplant for individuals with serious blood and immune disorders who lack a perfectly matched donor. The treatment uses a technique called CD3+/CD19+ depletion to prepare the stem cells, aiming to assist those with conditions like bone marrow failure or certain types of leukemia. It targets patients without a fully matched sibling donor who are ineligible for other similar treatments. Participants must have a serious condition requiring a stem cell transplant and a living donor ready to donate stem cells. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 protocol is safe for patients with bone marrow failure syndrome?

Research has shown that using stem cells with CD3+/CD19+ depletion in transplants is generally safe, though some risks exist. Studies have found that this method often leads to successful engraftment, where the transplanted cells effectively settle and grow in the patient's body. Engraftment rates range from 83% to 100%.

However, challenges can arise. Graft rejection, where the body does not accept the new cells, and graft-versus-host disease (GVHD), where the new cells attack the body, are possible issues. Despite these risks, GVHD is usually rare, and treatments for it are generally well-tolerated.

Overall, while risks exist, research suggests the treatment is manageable. Participants should consult trial doctors to fully understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for bone marrow failure syndrome, which often rely on fully matched sibling donors for stem cell transplants, this new approach uses a technique called CD3+/CD19+ depletion. This means that the process specifically removes certain immune cells from the donor stem cells, allowing patients without a fully matched sibling donor to still receive a transplant. Researchers are excited about this method because it expands the pool of potential donors and could make stem cell transplants accessible to more patients, potentially improving outcomes for those with limited options.

What evidence suggests that this stem cell transplant might be an effective treatment for bone marrow failure syndrome?

Research has shown that stem cell transplants using a technique called CD3+/CD19+ depletion hold promise for treating conditions like bone marrow failure syndrome. In this trial, participants will receive a transplant of stem cells with CD3+/CD19+ depletion. Studies indicate high success rates, with the new stem cells successfully settling in the patient's body, ranging from 83% to 100%. This method reduces the risk of graft-versus-host disease (GVHD), where donor cells attack the patient's body. Additionally, this approach results in fewer treatment-related deaths. Overall, early findings suggest this treatment could be a safe and effective option for patients needing a stem cell transplant without a fully matched donor. ^{1 2 3 4 5}

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 without a fully matched sibling donor who need a stem cell transplant due to serious conditions like leukemia, metabolic diseases correctable by HSCT, bone marrow failure, or immune system problems. They must meet specific health criteria and not be pregnant or have uncontrolled infections.

Inclusion Criteria

My organ functions meet the required levels, and I don't have an untreated infection.

You don't have a fully matched sibling for a specific type of stem cell transplant, and you don't meet the requirements for other treatment options at the hospital.

I am capable of becoming pregnant and have a negative pregnancy test.

Exclusion Criteria

My donor cannot give stem cells through their bloodstream.

I am currently pregnant.

I do not have any ongoing serious infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo allogeneic hematopoietic stem cell transplant (HSCT) with CD3+/CD19+ depleted stem cells

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after the transplant, focusing on complications such as graft vs. host disease (GVHD)

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transplant of stem cells with CD3+/CD19+ depletion (CliniMACs)

Trial Overview The trial provides access to a special stem cell transplant using CliniMACs technology to deplete certain cells (CD3+/CD19+) from the donated material. It's aimed at those who can't participate in other trials but need this potentially life-saving procedure.

How Is the Trial Designed?

Group I: Expanded access to CliniMACs device for T cell depletion Experimental Treatment 1 Intervention

access for patients who lack a fully HLA matched sibling, and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-open protocols that utilize CliniMACs technology for T depletion. Subjects will undergo transplant of stem cells with CD3+/CD19+ depletion.

Transplant of stem cells with CD3+/CD19+ depletion (CliniMACs) is already approved in European Union, United States for the following indications:

Approved in European Union as CD3+/CD19+ depleted PBSC for:

• Hematologic malignancies
• Hemoglobinopathies
• Primary immunodeficiencies

Approved in United States as CD3+/CD19+ depleted PBSC for:

• Hematologic malignancies
• Hemoglobinopathies
• Primary immunodeficiencies

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

In a study involving 33 children with high-risk acute myeloid leukemia (AML) who received TCR-alpha/beta and CD19-depleted grafts, primary engraftment was achieved in all patients, indicating the effectiveness of this graft manipulation method.

The cumulative incidence of acute graft-versus-host disease (aGvHD) was 39%, with a 10% transplant-related mortality rate, while the overall survival rate at 2 years was 67%, suggesting that this approach is both safe and effective for improving outcomes in pediatric AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Maschan, M., Shelikhova, L., Ilushina, M., et al.[2022]

The use of the CliniMACS Plus system for CD34+ cell enrichment in allogeneic stem cell transplantation achieved an average product purity of 95.66%, indicating a high-quality process that enhances the potential for using partially matched grafts without increasing the risk of graft-versus-host disease.

All end products tested negative for bacterial contamination and endotoxins, demonstrating the safety and reliability of the manufacturing process, which was validated across six different cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System. Kilic, P., Bay, M., Yildirim, Y., et al.[2020]

A novel treatment for severe combined immunodeficiency (SCID) using haploidentical hematopoietic stem cell transplantation (HSCT) with selective depletion of GvHD-inducing T-cells showed rapid engraftment and no signs of graft-versus-host disease (GvHD) in a 9-month-old patient.

The addition of donor lymphocyte infusion (DLI) enriched with memory T-cells effectively enhanced the patient's antiviral immunity, leading to increased T-cell counts and clearance of severe viral infections without causing GvHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions. Brodszki, N., Turkiewicz, D., Toporski, J., et al.[2018]

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]

Aggressive T-cell depletion is crucial for the success of haplo-identical stem cell transplantation, but traditional methods have resulted in high transplant-related mortality, with only a 20% overall survival rate.

The study found that while the recovery of CD34+ and NK cells was generally high, the T- and B-cell depletion process was not consistently effective, leading to the consideration of alternative protocols for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust. Wiercinska, E., Seifried, E., Bonig, H.[2021]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7122955/

PMC Search Update Combining pTCD with use of mobilized peripheral stem cells as a graft source has the added benefit of providing a much higher donor CD34+ stem ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05968170

TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide range of diagnoses including hematologic malignancies, bone marrow ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4828537/

Recent advances in haploidentical hematopoietic stem cell ... Many other studies showed that CD3/CD19 depletion could induce excellent primary engraftment rates, ranging from 83% to 100%, with acceptable GVHD and low TRM, ...

4. astctjournal.org astctjournal.org/article/S2666-6367(23)01321-0/fulltext

CD3+TCRαβ/CD19+-Depleted Mismatched Family or ... This single-center retrospective case series reports the outcomes of salvage CD3+TCRαβ/CD19-depleted mismatched family or unrelated donor stem ...

5. ashpublications.org ashpublications.org/blood/article/143/3/279/498045/TCR-CD19-cell-depleted-HLA-haploidentical

TCRαβ/CD19 cell–depleted HLA-haploidentical ... T-cell receptor (TCR)αβ/CD19 cell depletion has emerged as an effective graft manipulation strategy for preventing graft-versus-host disease ( ...