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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to reduce the risk of graft-versus-host disease, a complication where transplanted cells attack the body, in patients needing a stem cell transplant. The treatment uses a device called CliniMACS® (also known as the CliniMACS CD34 Reagent System) to remove certain cells from the donor's stem cells before transplantation. The trial seeks participants under 30 years old who need a stem cell transplant and have a willing and healthy donor. The researchers aim to determine if this method can safely assist patients who face challenges with traditional transplants. This unphased trial offers a unique opportunity to contribute to innovative research that could improve transplant outcomes.

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 the CliniMACS® Device is safe for stem cell transplant patients?

Research has shown that the CliniMACS® system, used to remove certain T-cells, may reduce the risk of graft-versus-host disease (GVHD) in patients requiring a stem cell transplant. Studies have found that this method can decrease both short-term and long-term GVHD without compromising transplant success. The FDA has approved the CliniMACS® system for specific uses, indicating its general safety and effectiveness in those situations. However, for other uses, such as in this trial, it is still under evaluation to ensure safety and effectiveness.

The treatment reduces harmful T-cells while preserving helpful stem cells, which helps lower the risk of GVHD. So far, no major safety issues have been reported in its approved uses, providing some confidence in its safety for new applications. Participants should feel comfortable asking questions during the trial to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for patients undergoing stem cell transplants involve using medications to prevent complications like graft-versus-host disease. However, the CliniMACS® T-cell depletion technique offers a unique approach by specifically removing alpha-beta T-cells from the stem cell product. This method targets specific T-cells responsible for causing complications while preserving beneficial cells, potentially reducing the risk of adverse effects. Researchers are excited about this technique because it could improve the safety and effectiveness of stem cell transplants, offering patients a more targeted and less risky treatment option.

What evidence suggests that the CliniMACS® device is effective for minimizing the risk of GVHD in stem cell transplant patients?

Research has shown that the CliniMACS® T-cell depletion system, which participants in this trial will receive, can lower the risk of graft-versus-host disease (GVHD) in patients undergoing stem cell transplants. Studies have found a high success rate in the new stem cells growing and producing healthy blood cells, with few complications. The system removes certain T-cells that can cause GVHD while preserving the essential CD34+ cells needed for a successful transplant. This approach has been linked to reduced short-term and long-term GVHD, leading to better overall patient outcomes. ^{2 3 5 6 7}

Who Is on the Research Team?

Christopher C Dvorak, MD

Principal Investigator

Professor of Clinical Pediatrics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. miltenyibiotec.com miltenyibiotec.com/US-en/products/clinimacs-cd34-reagent-system.html

CliniMACS® CD34 Reagent System | Miltenyi Biotec | USA This method of T cell depletion did not have any negative impact on engraftment success, patient survival, or relapse rate.3. Disclaimer. HUMANITARIAN DEVICE: ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/11/NCT02162511/Prot_SAP_000.pdf

AN EXPANDED ACCESS STUDY USING THE CLINIMACS ... CliniMACS® CD34+ Reagent System has the advantages of the best T cell depletion efficiency achievable and a very high efficiency of CD34+ cell recovery so that ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3762249/

Characteristics of CliniMACS® System CD34-Enriched T ... These studies have shown a high rate of engraftment, minimal transplant-related complications, and, in contrast to recipients of T cell depleted ...

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04337515

CLINIMACS® for Alpha/Beta T-Cell Depletion in Stem ... The CliniMACS® CD34 Reagent System is now indicated for processing hematopoietic progenitor cells collected by apheresis (PBSC) from an ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8432362/

Allogeneic Stem Cell Transplantation with CD34+ ... T cell depletion through positive selection of CD34+ cells has emerged as a promising strategy to reduce acute and chronic GvHD in these patients.

6. static.miltenyibiotec.com static.miltenyibiotec.com/asset/150655405641/document_h7ibembnnh6spdrrkvr78sao20/CliniMACS_CD34_US_healthcare_brochure

CliniMACS® CD34 Reagent System The CliniMACS® CD34 Reagent System reduces the risk of chronic GVHD in patients with AML without negatively impacting post-transplantation outcome. Major ...

7. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/IFU--CliniMACS%C2%AE-CD34-Reagent-System.pdf

CD34 Reagent System The safety of the CliniMACS® CD34 Reagent System was ... Low Risk of Chronic Graft-versus-Host Disease and. Relapse Associated with T Cell-Depleted Peripheral ...