Stem Cell Selection for Blood Diseases

Overseen By Lauren Harrison, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Mitchell Cairo

Disqualifiers: Pregnancy, Uncontrolled infection, Low performance, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Children, adolescents, and young adults with malignant and non-malignant conditionsundergoing an allogeneic stem cell transplantation (AlloSCT) will have the stem cells selected utilizing α/β CD3+/CD19+ cell depletion. All other treatment is standard of care.

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 treatment Alpha/Beta Depletion, Alpha/Beta T Cell Depletion, TCR αβ+ T Cell Depletion, α/β CD3+ T-cell and CD19+ B-cell depletion for blood diseases?

Research shows that TCR-alpha/beta and CD19 depletion is effective in engineering grafts for children with acute myeloid leukemia (AML), achieving a 100% primary engraftment rate and a 67% overall survival rate at 2 years. This suggests that the treatment can be a robust method for managing high-risk blood diseases. ^{1 2 3 4 5}

Is stem cell treatment with TCR-alpha/beta and CD19 depletion safe for humans?

Research shows that TCR-alpha/beta and CD19 depletion in stem cell treatments is generally safe, with low rates of severe complications like graft-versus-host disease (a condition where the donor cells attack the recipient's body) and non-relapse mortality (death not related to the return of the disease). ^{1 2 5 6 7}

How is the Alpha/Beta Depletion treatment unique for blood diseases?

The Alpha/Beta Depletion treatment is unique because it selectively removes specific immune cells (TCR alpha/beta+ T cells and CD19+ B cells) from donor stem cell grafts, which can help reduce complications like graft-versus-host disease (a condition where donor cells attack the recipient's body) while preserving beneficial cells like natural killer cells. This approach is particularly useful in stem cell transplants from partially matched donors, offering a more targeted and potentially safer alternative to traditional methods. ^{1 2 3 5 8}

Research Team

Mitchell S Cairo

Principal Investigator

New York Medical College

Eligibility Criteria

This trial is for children and young adults (0-30 years) with various blood diseases, including high-risk acute leukemia, lymphoma, sickle cell disease, and bone marrow failure syndromes. Participants must have adequate organ function and not be pregnant or breastfeeding. They can't join if they've had a recent transplant or uncontrolled infection.

Inclusion Criteria

I have Sickle Cell Disease.

I have been diagnosed with high-risk Myelodysplastic syndrome.

I have a bone marrow failure syndrome and treatments haven't worked for me.

Exclusion Criteria

I do not have any untreated infections.

I am not pregnant or breastfeeding.

I had a stem cell transplant from a donor less than 6 months ago, not as a boost.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive full intensity, reduced intensity, or reduced toxicity conditioning based on disease and other factors

2-3 weeks

Transplantation

Patients undergo α/β T-cell and CD 19+ B cell depleted allogeneic stem cell transplantation

1 week

Post-transplant Monitoring

Patients are monitored for engraftment, chimerism, immune reconstitution, GVHD, and QOL

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Alpha/Beta Depletion

Trial Overview The study tests a stem cell transplantation technique using α/β CD3+/CD19+ cell depletion in patients with malignant and non-malignant hematologic conditions. This method aims to improve outcomes by selecting specific cells while maintaining standard care treatments.

Participant Groups

Group I: alpha beta cell depletion Experimental Treatment 1 Intervention

Matched allogeneic donor stem cells will be processed utilizing α/β CD3+/CD19+ cell depletion with the Prodigy system. Standard pre-conditioning and post-transplant motioning will be given.

Alpha/Beta Depletion is already approved in United States, European Union for the following indications:

Approved in United States as CliniMACS CD34 Reagent System for:

• Acute Myeloid Leukemia (AML) in first complete remission undergoing allogeneic HCT from a matched related donor

Approved in European Union as CliniMACS System for:

• Hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional GVHD prophylaxis in patients with AML in first morphologic complete remission (CR1)

Who Is Running the Clinical Trial?

Mitchell Cairo

Lead Sponsor

Trials

2

Recruited

60+

Findings from Research

In a study of 273 patients receiving T cell-depleted marrow using the T10B9 antibody, higher doses of TCR gamma delta + T cells were significantly associated with better engraftment probabilities, suggesting their beneficial role in the transplantation process.

TCR alpha beta + T cells were linked to a higher risk of acute graft-versus-host disease (GVHD) in recipients of related donor marrow, while TCR gamma delta + T cells did not increase this risk, indicating that different T cell subsets have distinct impacts on engraftment and GVHD outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation. Kawanishi, Y., Passweg, J., Drobyski, WR., et al.[2006]

Aggressive T-cell depletion is crucial for the success of haplo-identical stem cell transplantation, but traditional methods have resulted in high transplant-related mortality, with only a 20% overall survival rate.

The study found that while the recovery of CD34+ and NK cells was generally high, the T- and B-cell depletion process was not consistently effective, leading to the consideration of alternative protocols for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust. Wiercinska, E., Seifried, E., Bonig, H.[2021]

Plerixafor significantly improved the collection of CD34+ hematopoietic progenitor cells in pediatric allogeneic donors, achieving a median increase of 14.8-fold in poor mobilizers and 6.5-fold in insufficient mobilizers, compared to a 3.45-fold increase with G-CSF alone.

The use of plerixafor was safe, with only mild to moderate side effects reported, and it did not compromise the purity of TCR-alpha/beta depletion in the apheresis product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor added to G-CSF allows mobilization of a sufficient number of hematopoietic progenitors without impacting the efficacy of TCR-alpha/beta depletion in pediatric haploidentical and genoidentical donors failing to mobilize with G-CSF alone. Kurnikova, E., Trakhtman, P., Pershin, D., et al.[2022]

A study of 506 adult patients receiving CD34+ selected hematopoietic stem cell transplants showed that using a combined prognostic model of Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) can effectively predict overall survival and relapse-free survival outcomes.

Patients with a high DRI had a significantly increased risk of death and relapse compared to those with low/intermediate DRI, indicating that this model can help in selecting the best candidates for CD34+ selected transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. Cho, C., Hilden, P., Avecilla, ST., et al.[2022]

In a study involving 33 children with high-risk acute myeloid leukemia (AML) who received TCR-alpha/beta and CD19-depleted grafts, primary engraftment was achieved in all patients, indicating the effectiveness of this graft manipulation method.

The cumulative incidence of acute graft-versus-host disease (aGvHD) was 39%, with a 10% transplant-related mortality rate, while the overall survival rate at 2 years was 67%, suggesting that this approach is both safe and effective for improving outcomes in pediatric AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Maschan, M., Shelikhova, L., Ilushina, M., et al.[2022]

In a study involving 213 children with acute leukemia, TCRαβ/CD19 cell depletion during HLA-haploidentical hematopoietic stem cell transplantation showed promising long-term outcomes, with a projected 10-year overall survival rate of 75.4% and a disease-free survival rate of 71.6%.

The incidence of severe complications such as acute and chronic graft-versus-host disease was low (14.7% and 8.1%, respectively), indicating that this graft manipulation technique is both safe and effective for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCRαβ/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis. Merli, P., Algeri, M., Galaverna, F., et al.[2023]

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 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]

References

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

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation. [2006]

2. England pubmed.ncbi.nlm.nih.gov

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust. [2021]

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

Plerixafor added to G-CSF allows mobilization of a sufficient number of hematopoietic progenitors without impacting the efficacy of TCR-alpha/beta depletion in pediatric haploidentical and genoidentical donors failing to mobilize with G-CSF alone. [2022]

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

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. [2022]

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

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. [2022]

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

TCRαβ/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis. [2023]

7. China 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]. [2017]

8. Switzerland 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. [2022]