CD34+ Stem Cells for Graft Failure

Overseen By Kelsey Stocker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Disqualifiers: Disease relapse, Donor unavailable, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

21 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed trial is a single arm, non-randomized, single center pilot study utilizing CliniMACS CD34 Reagent System for patients following allogeneic hematopoietic stem cell transplant (HSCT) requiring treatment of graft dysfunction or failure.

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

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the CD34+ Selected Stem Cell treatment for graft failure?

Research shows that CD34+ selected stem cells can lead to rapid and lasting engraftment, meaning they help the body accept and use the new cells effectively. The CliniMACS system used in this treatment has been shown to produce high-purity CD34+ cells, which are important for successful stem cell transplants, and reduces the risk of complications like graft-versus-host disease. ^{1 2 3 4 5}

Is CD34+ stem cell treatment safe for humans?

CD34+ stem cell treatments, such as those using the CliniMACS system, have been shown to be generally safe in humans, with studies reporting no severe complications in the first 100 days and an acceptable safety profile. These treatments have been used in various conditions, including high-risk patients, with careful monitoring and controlled procedures to ensure safety. ^{1 2 6 7 8}

What makes the CD34+ Selected Stem Cell treatment unique for graft failure?

The CD34+ Selected Stem Cell treatment is unique because it involves selecting and enriching CD34+ stem cells, which can lead to rapid and durable engraftment with less toxicity due to a smaller infusion volume. This method also reduces the risk of complications like graft-versus-host disease by depleting T-cells and potentially tumor cells, making it safer for partially matched transplants. ^{1 2 3 4 9}

Research Team

Jingmei Hsu

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for patients who have had a stem cell transplant from another person (allogeneic HSCT) but are experiencing poor graft function or complete graft failure. Specific eligibility details are not provided, so it's important to contact the study team for more information.

Inclusion Criteria

Negative pregnancy test within seven (7) days of product infusion for women of childbearing potential

I am an adult who has received a transplant from a donor, regardless of the match.

Transplanted donor availability

Exclusion Criteria

Allergic reaction to murine proteins or iron dextran

Women of childbearing potential with positive serum HCG

I don't have a donor available for stem cell collection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a single infusion of CD34 selected HSCT from the original donor

1 day

1 visit (in-person)

Follow-up

Participants are monitored for engraftment and GvHD up to Day 100 post-procedure

14 weeks

Regular visits as per institutional standards

Extended Follow-up

Participants are monitored for chronic GvHD up to Day 365 post-procedure

52 weeks

Treatment Details

Interventions

• CD34+ Selected Stem Cell

Trial Overview The trial is testing a procedure where CD34+ cells, which are a type of stem cell, are selected and then given back to the patient to see if this can improve how well the transplanted cells work or fix cases where they've stopped working.

Participant Groups

Group I: Individuals with Poor Graft Function or Failure Following Allogeneic HSCT Experimental Treatment 2 Interventions

The recipient will undergo evaluations, then undergo a single infusion of CD34 selected HSCT from the original donor. No additional GvHD prophylaxis will be administered. Patients who develop GvHD will receive the standard of care based on the discretion of the treating physician . Patients will receive supportive care per institutional standards and at the discretion of the treating physician.

CD34+ Selected Stem Cell is already approved in United States for the following indications:

Approved in United States as CliniMACS CD34 Reagent System for:

• Acute Myeloid Leukemia (AML) in first morphologic complete remission

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

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 avidin-biotin immunoadsorption technique effectively selects CD34+ progenitor cells from bone marrow and mobilized peripheral blood, leading to rapid and durable engraftment in clinical studies.

Using CD34+ selected cells results in significantly less infusional toxicity for patients due to the smaller volume of cells compared to traditional methods, and it also allows for additional benefits like T-cell and tumor cell depletion, enhancing the safety and efficacy of cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of CD34+ hematopoietic progenitor cells. Berenson, RJ., Shpall, EJ., Auditore-Hargreaves, K., et al.[2019]

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 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]

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 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]

CD34-selected stem cell boost (SCB) significantly improves outcomes in patients with poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), achieving a complete response rate of 72% and an overall response rate of 80% based on a review of 7 studies involving 209 patients.

The treatment has an acceptable safety profile, with incidences of acute and chronic graft-versus-host disease (GVHD) at 17% and 18%, respectively, indicating that while there are risks, the benefits of SCB in improving survival rates (54% at 42 months) are notable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis. Shahzad, M., Siddiqui, RS., Anwar, I., et al.[2021]

The UNMC protocol for CD34(+) cell enumeration demonstrated better performance than the ISHAGE method, showing a larger dynamic range and improved correlation with CFU-GM results across all measured doses.

The UNMC method also exhibited superior inter-technologist reproducibility, with a coefficient of variation of 7%, compared to 23% for the ISHAGE method, indicating it may be a more reliable technique for assessing graft hematopoietic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of ISHAGE protocol CD34 cell enumeration with a lineage negative backgating technique. Pirruccello, SJ., Page, CJ., Bishop, MR., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Transplantation of CD34+ hematopoietic progenitor cells. [2019]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. [2021]

7. 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]

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

Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of ISHAGE protocol CD34 cell enumeration with a lineage negative backgating technique. [2018]