Stem Cell Transplant for Blood Cancer

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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This single arm pilot phase I study with safety run-in is designed to estimate the safety and efficacy of a familial mismatched or haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a novel graft modification technique (selective αβ-TCR and CD19 depletion).

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 data supports the idea that Stem Cell Transplant for Blood Cancer is an effective treatment?

The available research shows that Stem Cell Transplant for Blood Cancer, specifically using the TCRαβ/CD19 depletion method, is effective. In a study involving 213 children with acute leukemia, the treatment showed promising results with a 5-year survival rate of 75.4% and a disease-free survival rate of 71.6%. Additionally, the risk of severe complications was low, with only 14.7% experiencing significant acute issues and 8.1% having chronic problems. This suggests that the treatment is effective and has outcomes similar to those from matched donor transplants. Another study highlighted rapid recovery and improved immune function in pediatric patients, further supporting its effectiveness. ^{1 2 3 4 5}

What safety data is available for stem cell transplants using TCR-alpha/beta and CD19 depletion?

The safety data for TCR-alpha/beta and CD19 depletion in stem cell transplants shows promising results. Studies report low non-relapse mortality rates, low incidences of acute and chronic GvHD, and good overall survival rates. For example, a study on pediatric acute leukemia patients showed a 5-year non-relapse mortality of 5.2% and a 10-year overall survival of 75.4%. Another study on children with AML reported a 2-year overall survival of 67% and event-free survival of 60%. These results suggest that this method is effective and relatively safe, with manageable risks of GvHD and transplant-related mortality. ^{1 2 3 4 6}

Is the treatment Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus a promising treatment for blood cancer?

Yes, this treatment is promising for blood cancer. It has shown good survival rates and low complications in patients, especially children with leukemia. The process helps in successful stem cell transplants by reducing harmful immune reactions, leading to better outcomes. ^{1 2 3 6 7}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

Donor must meet selection criteria defined by FACT

Timeline

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

Treatment Details

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.

Participant Groups

Group I: 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.

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product. [2023]

2. 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]

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

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

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

Haploidentical hematopoietic stem cell transplantation with αβTCR+/CD19+ depletion in pediatric patients with malignant and non-malignant disorders. [2022]

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

Haploidentical bone marrow transplantation in Mexico. [2012]

6. 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]

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

Generation and flow cytometric quality control of clinical-scale TCRαβ/CD19-depleted grafts. [2017]