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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to prepare stem cells for children, adolescents, and young adults needing a stem cell transplant for certain blood conditions. The goal is to determine if alpha/beta depletion, a technique that removes specific cells from donor stem cells, can improve outcomes for patients with conditions like leukemia, lymphoma, sickle cell disease, or bone marrow failure syndromes. Suitable candidates include individuals aged 0-30 with these conditions who have tried other treatments but still need assistance. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 Alpha/Beta Depletion is safe for children, adolescents, and young adults undergoing allogeneic stem cell transplantation?

Research has shown that reducing certain immune cells is generally safe for people receiving stem cell transplants from donors. In studies, patients have tolerated this treatment well. For example, one study found that removing specific T-cells and B-cells in transplants is a safe option for treating blood diseases. Another study demonstrated that this method remains safe even with donors who are not a perfect match. While some side effects may occur, these studies suggest that the treatment is overall manageable for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for blood diseases, which often involve chemotherapy and radiation, alpha/beta cell depletion uses a novel approach by specifically targeting and removing certain T-cells from donor stem cells. This method reduces the risk of graft-versus-host disease, a common complication in stem cell transplants. Researchers are excited because this technique could increase the safety and success rate of transplants, offering a more targeted and potentially less harmful treatment option for patients.

What evidence suggests that Alpha/Beta Depletion might be an effective treatment for blood diseases?

Research has shown that removing certain immune cells, called alpha/beta T-cells and CD19+ B-cells, may help reduce complications after stem cell transplants. This method, tested in this trial as alpha/beta cell depletion, can lower the risk of graft-versus-host disease, where transplanted cells attack the patient's body. In one study, patients who received this treatment experienced better recovery of their immune systems. Another study found it effective in preventing serious transplant-related problems in children with leukemia. Overall, these findings suggest that removing these specific cells could improve the success of stem cell transplants for various blood diseases. ^{1 2 6 7 8}

Who Is on the Research Team?

Mitchell S Cairo

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05800210

NCT05800210 | Alpha/Beta T Cell and CD19+ B ... This study will assess the safety, efficacy, and feasibility of ⍺/β CD3+ T-cell and CD19+ B-cell depletion in allogeneic stem cell transplantation in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6764418/

TCR αβ+/CD19+ cell depletion in haploidentical ... One of the strategies used for haploidentical transplants involves selective depletion of T cells expressing the αβ T cell receptor and CD19+ B cells prior to ...

3. ashpublications.org ashpublications.org/blood/article/143/3/279/498045/TCR-CD19-cell-depleted-HLA-haploidentical

TCRαβ/CD19 cell–depleted HLA-haploidentical ... T-cell receptor (TCR)αβ/CD19 cell depletion has emerged as an effective graft manipulation strategy for preventing graft-versus-host disease ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4211312/

Alpha/Beta T-Cell Depleted Grafts as an Immunological ... In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts.

5. isct-cytotherapy.org isct-cytotherapy.org/article/S1465-3249(25)00785-6/fulltext

Very early recovery of T cells after alpha/beta T ... In this retrospective study, we've focused on a homogeneous cohort of 262 children with acute leukemia first transplanted in complete remission, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864664/

Unrelated donor α/β T cell– and B cell–depleted HSCT for ... URD HSCT with TCRαβ/CD19 depletion is a safe and effective approach to alternative donor transplantation for hematologic malignancies.

7. isct-cytotherapy.org isct-cytotherapy.org/article/S1465-3249(25)00808-4/fulltext

Long-term outcomes of αβ T-cell/CD19 B-cell-depleted ... We investigated the role of alpha/beta T cell depletion of the graft as a way to improve the results of MUD HSCT in SAA. Patients and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8702395/

Results of a multicenter phase I/II trial of TCRαβ and CD19- ... Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.