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

Trial Summary

What is the purpose of this trial?

Participants are being asked to take part in this study because treatment of his or her disease requires a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation. Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) for the participant and his or her disease does not permit enough time to identify another donor (like someone from a registry list that is not his or her relative) or another suitable donor has not been identified. However, a close relative of the patient has been identified whose stem cells are not a perfect match, but can be used. Alternatively, the patient may have already received a stem cell transplant but have evidence of mixed chimerism, which means some of the patient's own bone marrow cells are present, rather than all of the donor's cells. This may lead to an increased risk of the disease coming back. Or, the patient may have all donor cells but his or her bone marrow is not working very well, which may lead to frequent blood or platelet (cells that help in clotting blood) transfusions or infection. Regardless of the reason, it may be necessary to isolate stem cells from a haploidentical (half-match) donor in order to provide bone marrow function. Because the stem cells from the donor are only half-matched to the participant, the risk of graft-versus-host disease (GvHD) is very high. GvHD is a complication after transplant caused by donor T cells (graft) that attack the transplant recipient, and this complication can cause death after transplant. Thus, it is important that the donor's blood cells are treated to minimize cells that are most likely to attack the host's tissues. This is done by using a special device to capture the CD34+ stem cells from the donor's stem cell product prior to giving the cells to the host. This method minimizes the donor T cells, which are responsible for causing GvHD. Purpose: In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, investigators would like to specially treat the donor's blood cells to minimize the cells that are most likely to attack the patient's tissues.

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 CD34 Reagent System treatment for bone marrow transplant?

The CliniMACS CD34 Reagent System is effective in selecting CD34+ cells, which are important for successful stem cell transplants, by significantly improving CD34+ cell recoveries and reducing unwanted T cells. This system has been shown to increase the pool of potential donors and improve outcomes by reducing complications like graft-versus-host disease. ^{1 2 3 4 5}

Is the CD34-Selected Stem Cell Transplant generally safe for humans?

The CliniMACS CD34 selection system, used for stem cell transplants, has been shown to be safe in humans. It effectively reduces unwanted T cells, which can cause complications, and maintains high cell purity and viability. However, potential side effects include increased infection rates and delayed immune recovery. ^{2 4 6 7 8}

What makes the CliniMACS CD34 Reagent System treatment unique for bone marrow transplant?

The CliniMACS CD34 Reagent System is unique because it uses immunomagnetic beads to selectively isolate CD34+ stem cells, which helps reduce the risk of graft-versus-host disease (a condition where the donor cells attack the recipient's body) by removing unwanted T cells. This system is the only FDA-approved device for this purpose and offers improved recovery of CD34+ cells and significant reduction of T cells compared to older methods. ^{1 2 6 7 9}

Research Team

Robert Krance, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Known HIV positivity

I have severe graft-versus-host disease.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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]

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 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]

References

1. United States 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. [2021]

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

How do I perform hematopoietic progenitor cell selection? [2018]

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

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. [2020]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2019]

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

Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2004]