Stem Cell Transplant for Blood Cancer

Recruiting at 1 trial location

Overseen By Jeffrey Bednarski, M.D., Ph.D.

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Active non-hematologic malignancy, others

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

Compensation: Varies

Number of Visits: 1

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating certain blood cancers, such as leukemia, using specially prepared stem cells from a family member. The main goal is to determine if this innovative treatment, called Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus, is safe and effective. The trial seeks individuals who have had a type of leukemia or blood disorder, possibly in remission, and have a family member who can donate stem cells. Participants should not have an active infection or another major illness. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you cannot be on other investigational agents. It's best to discuss your specific medications with the trial team.

What prior data suggests that this graft modification technique is safe for stem cell transplantation?

Research has shown that removing certain immune cells using a special system is generally safe. This process removes harmful cells while preserving helpful stem cells. Studies indicate that this method aids in the recovery of important stem cells, comparable to other known treatments.

Other findings suggest that using these specially prepared stem cells is both safe and effective. Reports have shown low rates of complications like graft-versus-host disease (GVHD), where the new cells might attack the body, making it as safe as other types of stem cell transplants.

While this trial is still in its early stages, past studies generally support the safety of these techniques in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancer, which often rely on chemotherapy or traditional stem cell transplants, this new approach uses a specialized stem cell transplant technique. Researchers are excited about it because it involves a process called ex vivo T-cell receptor αβ and CD19+ depletion. This targets specific cells in the immune system that can cause complications after the transplant. By removing these cells before the transplant, this method aims to reduce the risk of graft-versus-host disease, potentially making the treatment safer and more effective for patients.

What evidence suggests that this novel graft modification technique could be effective for blood cancer?

Research has shown that a new method in stem cell transplants, called ex vivo T-cell receptor alpha-beta and CD19+ depletion, holds promise. This method is used in a type of transplant known as haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In this trial, participants will receive the ex vivo αβ-TCR/CD19 depleted haplo-HSCT. Studies have found that this method can reduce the risk of graft-versus-host disease (GVHD), a common complication where the donor's immune cells attack the patient's body. In children, results have been encouraging, with fewer cases of GVHD compared to older methods. This technique removes specific immune cells that might cause problems, making the transplant safer. Overall, these findings suggest that this approach could offer a safer option for patients needing stem cell transplants. ^{2 3 6 7 8}

Who Is on the Research Team?

Jeffrey Bednarski, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 30 years old with certain high-risk blood cancers or tumors who have a family member that can be a half-matched stem cell donor. They must have good heart, lung, liver, and kidney function and agree to use birth control if they can have children. Patients with uncontrolled illnesses, active infections, or those pregnant cannot join.

Inclusion Criteria

I can do most activities but need help with some.

I have a specific type of leukemia or myelodysplastic syndrome in a certain stage.

My heart, liver, kidneys, and lungs are all working well.

Exclusion Criteria

Recipient must not have an available matched related donor unless urgent transplantation is required

Recipient must not be pregnant and/or breastfeeding

I do not have cancer that has spread to my brain or outside the bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo standard of care conditioning regimen prior to HSCT

1-2 weeks

Transplantation

Infusion of ex vivo αβ-TCR/CD19 depleted haplo-HSCT from a stimulated peripheral stem cell source

Day 0

1 visit (in-person)

Post-Transplant Monitoring

Monitoring for safety, engraftment, and donor cell chimerism

100 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus
• αβ-TCR/CD19 cell depleted haploidentical hematopoietic stem cell graft

Trial Overview The study tests a new way of preparing donated stem cells from family members before transplanting them into patients. It involves removing specific immune cells (αβ-TCR+ T-cells and CD19+ B-cells) which may help reduce complications after the transplant.

How Is the Trial Designed?

Group I: Recipients: ex vivo αβ-TCR/CD19 depleted haplo-hematopoietic stem cell infusion (HSCT) Experimental Treatment 1 Intervention

* Patients will undergo standard of care conditioning regiment prior to HSCT * On Day 0, patients will undergo infusion of the ex vivo αβ-TCR/CD19 depleted haplo-HSCT from a stimulated peripheral stem cell source per institutional standard of care. Patients whose graft has a residual CD20+ count \> 1.0 x 10\^5 may receive a single infusion of rituximab on Day +1 at a dose of 375 mg/m\^2 at provider's discretion.

Group II: Donors: Active Control 1 Intervention

Donors who meet the eligibility criteria will be mobilized as per institutional standard practice using G-CSF 10 mcg/kg/day with leukapheresis to take place on Day 5. The target volume for collection is 20 L. Up to 4 days of pheresis are permitted to ensure target collection.

Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus is already approved in European Union, United States for the following indications:

Approved in European Union as Selective αβ-TCR and CD19 depletion for:

• Pediatric hematologic malignancies

Approved in United States as Selective αβ-TCR and CD19 depletion for:

• Pediatric hematologic malignancies

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

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]

Haploidentical hematopoietic stem cell transplantation using the αβTCR+/CD19+ depletion technique has shown promising results in pediatric patients, leading to rapid engraftment and improved immune recovery.

This method also presents a low risk of graft-versus-host disease (GVHD), making it a safer option for patients without a matched donor, although further research is needed to optimize conditioning regimens for better transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem cell transplantation with αβTCR+/CD19+ depletion in pediatric patients with malignant and non-malignant disorders. Bielorai, B., Jacoby, E., Varda-Bloom, N., et al.[2022]

A new automated process using the CliniMACS Prodigy successfully depletes alloreactive T cells from hematopoietic stem cell grafts, achieving a high depletion efficiency of 4 log for both CD45RA+ and TCRαβ/CD19+ cells with minimal manual intervention.

The resulting products maintain a high viability of over 90% for stem cells and retain important immune cells like TCRγδ+ and NK cells, which are crucial for immunological surveillance, making them suitable for haplo-identical hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product. Wiercinska, E., Quade-Lyssy, P., Hümmer, C., et al.[2023]

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]

A new 10-color quality control panel was developed to accurately quantify residual TCRαβ+ T cells and CD19+ B cells in stem cell grafts, which is crucial for preventing severe graft-versus-host disease (GvHD) after haploidentical stem cell transplantation (HSCT).

The immunomagnetic purification method achieved significant depletion of TCRαβ and CD19 cells, with recovery rates of 82.1% for stem cells, 67.1% for NK cells, and 72.7% for TCRγδ+ T cells, potentially improving transplantation outcomes by ensuring a safer graft composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation and flow cytometric quality control of clinical-scale TCRαβ/CD19-depleted grafts. Bremm, M., Cappel, C., Erben, S., 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]

Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes was performed on four Mexican children with hematological malignancies, showing successful engraftment in three out of four cases over a follow-up period of 9½ years.

Despite the successful engraftment, all patients experienced cytomegalovirus reactivation, and one child died due to graft rejection and infectious complications, highlighting the significant risk of infections associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical bone marrow transplantation in Mexico. Vázquez-Meraz, JE., Arellano-Galindo, J., Mendoza-García, E., et al.[2012]

Citations

1. 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 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0966327425000486

Comprehensive up-to-date analysis on TCRαβ/CD19 ... This meta-analysis assesses the efficacy of TCRαβ+/CD19+ depleted hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05011422?cond=Stem+Cell&aggFilters=status%3A

Study Details | Haploidentical Hematopoietic Stem Cell ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6521977/

Advances in Ex Vivo T Cell Depletion – Where Do We Stand? In this review we summarize methods and outcomes of ex vivo T cell depleted (TCD) HCT with a focus on CD34+ selection.

5. jacionline.org jacionline.org/article/S0091-6749%2817%2931202-2/fulltext

T-cell receptor αβ+ and CD19+ cell–depleted ... We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αβ CD3+ cells from the graft. Methods. CD3+ ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23993299/

Depletion of T-cell receptor alpha/beta and CD19 positive ... Profound depletion of TCRαβ(+) T cells can be achieved with the CliniMACS system. Recovery of CD34(+) stem cells is in the same range than after CD34(+) ...

7. researchgate.net researchgate.net/publication/256329960_Depletion_of_T-cell_receptor_alphabeta_and_CD19_positive_cells_from_apheresis_products_with_the_CliniMACS_device

Depletion of T-cell receptor alpha/beta and CD19 positive ... Profound depletion of TCRαβ(+) T cells can be achieved with the CliniMACS system. Recovery of CD34(+) stem cells is in the same range than after ...

8. 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 ...