CliniMACS® for Blood Cancers

(TB19DHCT Trial)

Overseen By Lauren Rayman

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Nationwide Children's Hospital

Disqualifiers: HIV, Uncontrolled infections, 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

Duration: 100 days

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for preparing stem cell transplants for children and young adults with blood cancers. The treatment uses a device called CliniMACS® (also known as the CliniMACS CD34 Reagent System) to sort and remove specific immune cells from donor stem cells before the transplant. This approach aims to make transplants from non-matching donors safer and more effective. The trial seeks participants under 30 who need a stem cell transplant and lack a perfectly matched sibling donor. As an unphased trial, this study offers the chance to contribute to pioneering research that could enhance transplant safety and effectiveness.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop 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 children and young adults with hematologic malignancies?

Research has shown that the CliniMACS® device, used to sort certain blood cells, has undergone testing in various studies. One study found that the device prepared cell grafts without any reported device-related issues. However, patients receiving these prepared cells faced risks, including serious viral infections. This indicates that while the treatment is generally well-tolerated, potential infection risks exist. Prospective participants should carefully weigh the benefits and risks before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for blood cancers, which often rely on chemotherapy or traditional bone marrow transplants, CliniMACS® offers a unique approach by using TCR αβ/CD19+ depleted grafts. This method selectively removes certain T-cells that can cause complications, potentially reducing the risk of graft-versus-host disease (GVHD) and making it safer for patients receiving transplants from alternative donors. Researchers are excited about CliniMACS® because it could expand the pool of eligible donors and improve outcomes for patients who might not have matched donors available.

What evidence suggests that the CliniMACS® device is effective for blood cancers?

Research has shown that the CliniMACS® system excels at purifying specific blood stem cells, achieving a median purity of 97.7%. This is crucial for patients undergoing a type of stem cell transplant. In this trial, participants will undergo allogeneic HSCT using TCR αβ/CD19+ depleted grafts with the CliniMACS® system. The system effectively removes certain immune cells (T and B cells) that can cause complications. Studies have demonstrated that this method helps recover a high number of necessary stem cells, making the transplant process safer and more successful for treating blood cancers. Overall, the CliniMACS® system is well-regarded in medical settings for its efficiency and effectiveness. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 30 years old with blood cancers who need a bone marrow transplant but don't have a matched sibling donor. They should be in good health otherwise, able to tolerate the transplant process, and have an acceptable performance status score.

Inclusion Criteria

I am 30 years old or younger.

I have a detailed HLA test result available.

I need a stem cell transplant for my blood cancer and don't have a matching sibling donor.

Exclusion Criteria

Patient reports a history of allergic reactions to murine protein

I do not have a suitable donor available for my treatment.

I am receiving a transplant from umbilical cord blood or a sibling match.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an allogeneic HSCT from a matched unrelated donor (MUD), mismatch unrelated donor (MMUD) or a mismatched related (haploidentical) donor following CliniMACS® αβT cell/CD19+B cell depletion

100 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and incidence of graft failure and GVHD

1 year

What Are the Treatments Tested in This Trial?

Interventions

• CliniMACS®

Trial Overview The study tests CliniMACS® device's ability to deplete specific immune cells (αβT/CD19+ B cells) from stem cell grafts before transplantation. It aims to see if this can help patients accept cells from partially matched or unrelated donors without complications.

How Is the Trial Designed?

Group I: HSCT using TCR αβ/CD19+ depleted grafts Experimental Treatment 1 Intervention

Allogeneic HSCT using the TCR αβ/CD19+ depleted platform and grafts from alternative donors (MUD, MMUD and haploidentical)

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?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Published Research Related to This Trial

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 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 system effectively purifies CD34+ peripheral blood stem cells (PBSC) from adult patients, achieving a median purity of 97.7% and a recovery rate of 69.5%, indicating its efficiency in reducing tumor cell contamination for autologous transplants.

The procedure demonstrated safety, as it did not affect the viability of the selected cells, and the subsequent autologous transplant showed a median time to neutrophil recovery of 12 days, supporting its use in patients with various malignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device. Després, D., Flohr, T., Uppenkamp, M., et al.[2019]

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]

In a study of 643 CliniMACS CD34-selection procedures, it was found that overloading tubing sets with excess total nucleated cells did not negatively impact the recovery and purity of CD34+ cells, allowing for more efficient processing.

The capacity of CliniMACS reagents was safely increased from 600 million to 1 billion CD34+ cells without compromising recovery, which can reduce processing time and costs for hematopoietic progenitor cell selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 'out-of-specification' CliniMACS CD34-selection procedures of hematopoietic progenitor cell-apheresis products. Braakman, E., Schuurhuis, GJ., Preijers, FW., et al.[2019]

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 CliniMACS Plus Instrument effectively isolates hematopoietic progenitor cells (HPCs) and other immune cells, achieving viable cell recovery rates between 32.3% and 65.4%, with the highest recovery for CD34+ selections.

Cell purity was notably high, ranging from 86.3% to 99.0%, particularly for CD4+ selections, indicating that the instrument is reliable for preparing cellular therapies, with optimization possible through adjustments in manufacturing variables.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument. Panch, SR., Reddy, OL., Li, K., et al.[2021]

Allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells in high-risk patients showed promising results, with 62.5% of patients alive and in remission after a median follow-up of 815 days.

The procedure was well tolerated, with no severe complications in the first 100 days, although 37.5% of patients experienced severe acute graft-versus-host disease (aGVHD) after receiving nonselected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. Markiewicz, M., Hołowiecki, J., Wojnar, J., et al.[2021]

The CliniMACS device effectively selects CD34+ cells from peripheral blood stem cells, achieving a median purity of 79% and a recovery rate of 66% in a study involving eight adult patients with hematologic malignancies.

This method significantly reduces T cell content from a median of 3.1 billion pre-selection to just 7.9 million post-selection, while maintaining high cell viability (98%), which is crucial for safe and effective autologous stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience. Leong, CF., Habsah, A., Teh, HS., et al.[2008]

Citations

1. miltenyibiotec.com miltenyibiotec.com/US-en/products/cell-therapy/clinimacs-cd34-reagent-system-fda-approved/health-care-professionals/clinical-data.html

Clinical data | Miltenyi Biotec | USA The CliniMACS® CD34 Reagent System was tested in a phase II single-arm multicenter study with a total of 37 patients in first morphologic complete remission ...

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324908701592

Evaluation of 'out-of-specification' CliniMACS CD34 ... In this retrospective evaluation of 643 CliniMACS CD34-selection procedures, we validated the capacity of CliniMACS tubing sets and CD34 reagent.

4. withpower.com withpower.com/trial/phase-neoplasms-11-2023-c8712

CliniMACS® for Blood Cancers (TB19DHCT Trial) The CliniMACS system effectively purifies CD34+ peripheral blood stem cells (PBSC) from adult patients, achieving a median purity of 97.7% and a recovery rate ...

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

CliniMACS® CD34 Reagent System | Miltenyi Biotec | USA The CliniMACS CD34 Reagent System is a medical device system that is designed for the in vitro enrichment of CD34 + target cells from heterogeneous hematologic ...

6. miltenyibiotec.com miltenyibiotec.com/US-en/products/cell-therapy/clinimacs-cd34-reagent-system-fda-approved/health-care-professionals/the-fda-approved-system/warnings-and-precautions.html

Warnings and precautions | Miltenyi Biotec | USA Patients who receive the CD34+ cell-enriched population prepared using the CliniMACS CD34 Reagent System are at risk for serious opportunistic viral infections, ...

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 potential risks of using the CliniMACS® CD34 Reagent. System were evaluated via a Data Analysis Protocol (DAP), which retrospectively compared the Day-100, ...