CD34-Selected Stem Cell Transplant for Bone Marrow Transplant

(EXCESS Trial)

Recruiting at 1 trial location

Overseen By Robert Krance, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: GvHD, Infection, HIV, 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: 30

241 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to make stem cell transplants safer and more effective by reducing the risk of graft-versus-host disease (GvHD), where donor cells attack the recipient's body. The CliniMACS CD34 Reagent System treats donor cells before transplant, targeting patients without a perfectly matched donor or those with mixed chimerism (presence of their own cells alongside donor cells) or poor bone marrow function. Potential participants have had a stem cell transplant but face issues like mixed chimerism, poor bone marrow function, or disease relapse.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for those encountering challenges after a stem cell transplant.

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 CD34 Reagent System is safe for stem cell transplantation?

Research has shown that the CliniMACS CD34 Reagent System is designed to lower the risk of graft-versus-host disease (GvHD), a serious condition where donor cells attack the patient's body after a stem cell transplant. Studies have found that this system effectively reduces the number of donor T cells, the main cause of GvHD.

Regarding safety, evidence suggests that the CliniMACS CD34 Reagent System is generally well-tolerated. However, serious side effects have occurred. For example, one study found that 2% of patients developed a severe condition called post-transplantation lymphoproliferative disorder, which was fatal in that instance. This highlights the importance of weighing both the benefits and risks of this treatment option.

Overall, the system has been used safely in various situations, but like any medical treatment, potential risks exist. Participants should consult their healthcare provider to understand how it might affect their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the CliniMACS CD34 Reagent System in stem cell transplants because it offers a promising approach to improve outcomes for patients with poor graft function or disease relapse after bone marrow transplants. Unlike standard treatments, which often involve just chemotherapy and radiation to prepare patients for stem cell transplants, this method uses CD34+ stem cells collected and purified, potentially leading to better integration and effectiveness. Especially intriguing is the system's ability to deliver these stem cells as a "top-off" treatment, either with or without additional conditioning, offering tailored treatment options based on patient needs. This flexibility and precision may enhance patient recovery and long-term success rates compared to traditional methods.

What evidence suggests that the CliniMACS CD34 Reagent System is effective for reducing graft-versus-host disease in bone marrow transplants?

Studies have shown that the CliniMACS CD34 Reagent System can lead to a high success rate in engraftment, meaning the new stem cells effectively start producing healthy blood cells. In this trial, participants in different cohorts will receive CD34+ cells processed with this system. Cohort 1 will receive CD34+ cells for transplant following a conditioning regimen, while Cohorts 2 and 3 will receive CD34+ cells as a "top off," with Cohort 3 requiring additional conditioning. This system also reduces T cells, which can cause graft-versus-host disease (GvHD), a serious condition where donor cells attack the patient's body. Research indicates that using CD34-selected stem cells results in fewer transplant-related complications. Specifically, patients have experienced fewer problems compared to those who received transplants without this special cell processing. Overall, the CliniMACS CD34 System shows promise in improving the success and safety of stem cell transplants. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert Krance, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients needing a stem cell transplant who don't have a perfect match donor. It's open to individuals from birth to 70 years old, with mixed chimerism or poor bone marrow function after an initial transplant, or those requiring additional cellular therapy due to relapsed disease.

Inclusion Criteria

My bone marrow is not functioning well.

My condition has come back or hasn't improved.

I can understand and sign the consent form myself or have someone who can.

Exclusion Criteria

Known HIV positivity

I do not have a severe or life-threatening infection.

I have severe graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stem Cell Collection

Stem cells are collected from a haploidentical donor and processed using the CliniMACS CD34 Reagent System

1-2 weeks

1 visit (in-person)

Transplantation

Participants receive CD34+ selected peripheral blood stem cell transplant with or without conditioning

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GvHD after transplant

1 year

Visits on days 28, 60, 100, 180, and 365 post-transplant

What Are the Treatments Tested in This Trial?

Interventions

• CliniMACS CD34 Reagent system

Trial Overview The CliniMACS CD34 Reagent System is being tested. This system treats the donor's blood cells before transplantation in order to reduce graft-versus-host disease (GvHD) by isolating 'good' stem cells and minimizing T cells that could attack the patient's body.

How Is the Trial Designed?

Group I: Cohort 3: CD34+ cells as a top off With Conditioning Experimental Treatment 1 Intervention

Cohort 3 consists of patients needing additional CD34+ stem cells collected by 'CliniMACS CD 34+ Reagent System' as a "topoff" with the need for additional conditioning prior to the infusion. These patients who have already received SCT with conditioning and are receiving CD34+ cells from their original donor for poor graft function, declining chimerism or disease relapse.

Group II: Cohort 2: CD34+ cells as a top off Without Conditioning Experimental Treatment 1 Intervention

Cohort 2 consists of patients needing additional CD34+ stem cells collected by 'CliniMACS CD34 Reagent system' as a "topoff" without the need for additional conditioning prior to the infusion. These patients who have already received SCT and are receiving CD34+ cells from their original donor for poor graft function, declining chimerism or disease relapse.

Group III: Cohort 1: CD34+ Cells for transplant Experimental Treatment 1 Intervention

Cohort 1 consists of patients receiving CD34+ selected peripheral blood stem cell transplant with a preceding conditioning regimen (chemotherapy with, or without, radiation). The stem cells will then be separated out from the white blood cells by a special machine- called a CliniMACS CD34 Reagent System in the laboratory.

CliniMACS CD34 Reagent system is already approved in United States, European Union for the following indications:

Approved in United States as CliniMACS CD34 Reagent System for:

• Hematopoietic stem cell transplantation for various hematologic diseases
• Treatment of graft failure following allogeneic hematopoietic stem cell transplant

Approved in European Union as Miltenyi CliniMACS CD34 Selection Device for:

• Allogeneic hematopoietic stem cell transplantation for hematologic diseases
• Stem cell boosting in the setting of graft failure

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

The Miltenyi CliniMACS cell isolation system significantly improves the recovery of CD34+ hematopoietic stem/progenitor cells by 50%-100% while consistently reducing unwanted CD3+ T-cells by 3 logs, enhancing the safety and efficacy of stem cell transplants.

Despite the benefits of HPC selection in increasing donor pools and potentially reducing graft-versus-host disease, there are risks such as primary graft failure and increased infection rates, which must be carefully managed before implementing these techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do I perform hematopoietic progenitor cell selection? Avecilla, ST., Goss, C., Bleau, S., et al.[2018]

The CliniMACS CD34+ selection device effectively isolates high-purity CD34+ progenitor cells from apheresis products, achieving a median purity of 97% and a median viability of 99% across 71 separations from both autologous and allogeneic sources.

The device also demonstrates extensive T cell depletion, with only 0.04% residual CD3+ cells remaining, making it a promising tool for enhancing the safety and efficacy of stem cell transplants in patients with malignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device. Schumm, M., Lang, P., Taylor, G., et al.[2006]

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]

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 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 can effectively select CD34+ cells from mobilized peripheral blood stem cell concentrates, achieving a high proportion of CD34+ cells similar to the semiautomated CliniMACS Plus Instrument.

However, the recovery rate of CD34+ cells and the depletion of unwanted CD3+ cells were lower with the automated Prodigy compared to the semiautomated method, indicating potential areas for improvement in the automated process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates. Stroncek, DF., Tran, M., Frodigh, SE., et al.[2021]

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 CliniMACS device produced a higher purity of CD34+ cells (90% vs 78%) and lower T-cell content (0.06% vs 0.44%) compared to the Isolex 300i, indicating better selection efficiency.

Despite the higher purity from CliniMACS, the Isolex 300i showed greater functional capacity, with a higher recovery of colony-forming units and better expansion of progenitor cells, attributed to lower levels of apoptotic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variable product purity and functional capacity after CD34 selection: a direct comparison of the CliniMACS (v2.1) and Isolex 300i (v2.5) clinical scale devices. Watts, MJ., Somervaille, TC., Ings, SJ., et al.[2019]

The study evaluated immunomagnetic selection of CD34+ cells in 55 subjects, showing that a new octapeptide releasing agent achieved a significantly higher median purity of 98.5% compared to the traditional chymopapain method, which had a purity of 85.8%.

Both semi-automated and fully automated systems provided similar results in terms of CD34+ cell purity and yield, but the fully automated system significantly reduced the time and labor needed for the selection process, enhancing the efficiency of preparing cells for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enrichment of peripheral blood CD34+ cells for transplantation using a fully automated immunomagnetic cell selection system and a novel octapeptide releasing agent. Marolleau, JP., Dal Cortivo, L., Mills, B., et al.[2004]

Citations

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

CliniMACS® CD34 Reagent System | Miltenyi Biotec | USA The effectiveness of the device for this use has not been demonstrated. The CliniMACS® CD34 Reagent System is indicated for processing hematopoietic progenitor ...

2. miltenyibiotec.com miltenyibiotec.com/US-en/products/cell-therapy/clinimacs-cd34-reagent-system-fda-approved/health-care-professionals/the-fda-approved-system/clinimacs-cd34-reagent-system-technology.html

CliniMACS CD34 Reagent System Technology The CliniMACS CD34 Reagent System is indicated for processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA- ...

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

CD34 Reagent System The CD34 Reagent System is a medical device for preparing CD34+ cells, used for treatment of AML in first remission, and is a viscous, colloidal solution.

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

AN EXPANDED ACCESS STUDY USING THE CLINIMACS ... A CD34-positive selection device – Miltenyi CliniMACS® (15), Isolex (3) – was used to select stem cells and deplete T lymphocytes. Patients received a median of ...

5. 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 ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/44/NCT03093844/ICF_001.pdf

Safety and efficacy of Miltenyi CliniMACS® CD34 Reagent ... The study requires stem cell selection using a device called the Miltenyi CliniMACS® CD34. Reagent System. The device is not FDA approved for ...

7. static.miltenyibiotec.com static.miltenyibiotec.com/asset/150655405641/document_e92cbvqs1p4dh07vljo0ipad08?content-disposition=inline

CliniMACS CD34 Reference List Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.