CliniMACS® T-Cell Depletion for Stem Cell Transplant Patients

Overseen By Christopher C. Dvorak, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Christopher Dvorak

Disqualifiers: Pregnant, Life expectancy <1 month, 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

Duration: Up to 30 days

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients in need of an allogeneic hematopoietic cell transplant (HCT) are at risk of developing graft-versus-host-disease (GVHD). In certain clinical situations, the optimal approach to minimize the risk of GVHD is to perform ex vivo alpha-beta T-cell depletion of the donor cells. However, the CliniMACS® Device is FDA-approved only for a narrow indication. All other uses of ex vivo processed cells must be done under a feasibility study protocol.

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 CliniMACS® T-Cell Depletion treatment for stem cell transplant patients?

Research shows that the CliniMACS system effectively purifies and recovers CD34+ cells (important stem cells) while efficiently removing T cells, which can help reduce complications in stem cell transplants. This method has been used successfully in both children and adults with severe blood disorders and autoimmune diseases, showing higher purity and recovery rates compared to other methods. ^{1 2 3 4 5}

Is CliniMACS® T-Cell Depletion safe for humans?

The CliniMACS® system, used for T-cell depletion in stem cell transplants, has shown consistent safety in studies, with no endotoxins (harmful substances) detected and negative results for bacterial contamination. It has been used successfully in both children and adults for various conditions, indicating a generally safe profile. ^{1 2 3 5 6}

How is the CliniMACS® treatment different from other treatments for stem cell transplant patients?

The CliniMACS® treatment is unique because it uses a magnetic separation technique to efficiently deplete T cells from stem cell grafts, resulting in higher purity and recovery of CD34+ cells compared to other methods. This approach helps reduce the risk of complications like graft-versus-host disease in stem cell transplants. ^{1 2 3 5 7}

Research Team

Christopher C Dvorak, MD

Principal Investigator

Professor of Clinical Pediatrics

Eligibility Criteria

This trial is for males and females aged 0-30 needing a stem cell transplant due to certain diseases, with donors available who can give bone marrow or blood stem cells. It's not for those with identical related donors (unless they have Fanconi Anemia), life expectancy under one month, mouse protein or iron dextran allergies, pregnant/breastfeeding individuals, or if birth control isn't used.

Inclusion Criteria

Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

I have a healthy donor ready to give bone marrow or stem cells.

My condition requires a stem cell transplant.

Exclusion Criteria

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study

I have a healthy, willing, and HLA-matched relative to donate (unless I have Fanconi Anemia).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alpha-beta T-cell depleted stem cell transplants using the CliniMACS system

Up to 30 days

Multiple visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including engraftment and GVHD evaluations

12 months

Regular visits for monitoring and assessments

Long-term follow-up

Participants are monitored for long-term outcomes such as transplant-related mortality and chronic GVHD

12 months

Treatment Details

Interventions

• CliniMACS®

Trial Overview The study tests the CliniMACS® Device's ability to remove specific T-cells from donor cells before transplant to prevent graft-versus-host disease. This process is being evaluated as it's currently only FDA-approved for limited use and needs further investigation in other settings.

Participant Groups

Group I: Patients receiving allogeneic hematopoietic cell transplant Experimental Treatment 1 Intervention

The test product is a stem cell product which has been alpha-beta T- cell depleted using the CliniMACS system. Alpha-beta T-cell depleted cells are given intravenously over a period of time as dictated by the final volume of the infused product (5 ml/kg/hour). The target dose of CD34+ cells is ≥20x10\^6/kg, but a minimum of ≥2.5x10\^6/kg is required. The target dose of T-cell receptor (TCR) alpha-beta CD3+ cells is ≤1x10\^5/kg.

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

Approved in United States as CliniMACS CD34 Reagent System for:

• Prevention of graft-versus-host disease (GVHD) in patients with acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic cell transplant from a matched related donor

Approved in European Union as CliniMACS System for:

• Available as CE-marked medical devices for various cell separation and processing applications, but specific indications are not detailed beyond general use for hematopoietic cell processing

Who Is Running the Clinical Trial?

Christopher Dvorak

Lead Sponsor

Trials

2

Recruited

90+

Findings from Research

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 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]

The CliniMACS Prodigy system successfully automates the selection of CD34+ hematopoietic stem cells (HSCs) from apheresis products, achieving a high recovery rate of 74% with excellent cell viability of 99.9%.

The automated process maintains comparable quality to previous manual methods, ensuring similar CD34+ cell recovery and T-cell content, making it suitable for routine clinical use in generating T-cell-depleted stem cell grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated CD34+ cell isolation of peripheral blood stem cell apheresis product. Spohn, G., Wiercinska, E., Karpova, D., et al.[2018]

Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes was performed on four Mexican children with hematological malignancies, showing successful engraftment in three out of four cases over a follow-up period of 9½ years.

Despite the successful engraftment, all patients experienced cytomegalovirus reactivation, and one child died due to graft rejection and infectious complications, highlighting the significant risk of infections associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical bone marrow transplantation in Mexico. Vázquez-Meraz, JE., Arellano-Galindo, J., Mendoza-García, E., et al.[2012]

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]

Using the larger capacity tubing set (LS) for CD34(+) enrichment from cord blood units (CBU) resulted in significantly higher recovery rates (56% vs. 45%) and better cell viability (74% vs. 59%) compared to the standard tubing set (TS).

The study involved processing 46 freshly collected CBUs and found that the choice of tubing set and the age of the unit were the main factors influencing the efficiency of CD34(+) cell recovery and viability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved immunomagnetic enrichment of CD34(+) cells from umbilical cord blood using the CliniMACS cell separation system. Blake, JM., Nicoud, IB., Weber, D., et al.[2021]

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. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System. [2020]

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

Automated CD34+ cell isolation of peripheral blood stem cell apheresis product. [2018]

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

Haploidentical bone marrow transplantation in Mexico. [2012]

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

Improved immunomagnetic enrichment of CD34(+) cells from umbilical cord blood using the CliniMACS cell separation system. [2021]

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]