Haploidentical Stem Cell Transplant for Blood Diseases

Overseen By Jade Hanson, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins All Children's Hospital

Disqualifiers: Pregnancy, HIV, Active infections, 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: 1

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.

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 TCR Alpha Beta T-cell Depleted Haploidentical Hematopoietic Cell Transplantation?

Research shows that this treatment method, which involves removing specific immune cells to reduce complications, has been used successfully in children with blood cancers and other disorders. It has demonstrated rapid recovery of the immune system, low risk of complications, and satisfactory outcomes in patients who do not have a fully matched donor. ^{1 2 3 4 5}

Is TCR Alpha Beta T-cell Depleted Haploidentical Stem Cell Transplantation generally safe for humans?

Research shows that TCR Alpha Beta T-cell Depleted Haploidentical Stem Cell Transplantation 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). Studies in children with leukemia and other disorders have shown promising safety outcomes, with low non-relapse mortality and manageable side effects. ^{2 3 4 6 7}

How is the TCR Alpha Beta T-cell Depleted Haploidentical Hematopoietic Cell Transplantation treatment different from other treatments for blood diseases?

This treatment is unique because it involves selectively removing specific immune cells (TCR alpha beta T-cells and CD19+ B-cells) from the donor graft, which helps reduce the risk of complications like graft-versus-host disease while preserving beneficial cells that aid in recovery and fighting infections. ^{1 2 3 4 8}

Research Team

Deepak Chellapandian, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Eligibility Criteria

This trial is for children with severe blood diseases like sickle cell, thalassemia, and bone marrow failure who haven't responded to other treatments. They must have specific symptoms or complications of their condition. Kids can't join if they've had a solid organ transplant, active GVHD from previous transplants, an available HLA-matched sibling donor, are pregnant/breastfeeding, have HIV or uncontrolled infections.

Inclusion Criteria

I have a bone marrow condition or an autoimmune blood issue.

I have a half-matched donor for a transplant.

Signed written informed consent

Exclusion Criteria

I have a sibling who matches my HLA type and can donate bone marrow.

Pregnant or breastfeeding females

I have a blood disorder but no liver conditions that would exclude me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo TCR alpha beta and CD19 depleted stem cell transplantation from haploidentical donors

Immediate procedure

1 visit (in-person)

Engraftment Monitoring

Monitoring of donor engraftment and recovery of lymphocyte subpopulations

100 days

Regular visits (in-person)

Follow-up

Participants are monitored for transplant-related complications, infections, and overall survival

Up to 2 years

Periodic visits (in-person)

Treatment Details

Interventions

• TCR Alpha Beta T-cell Depleted Haploidentical HCT

Trial Overview The study tests a new type of stem cell transplant from half-matched family donors using TCR alpha beta and CD19 depleted grafts. It aims to see if this method is safe and effective in treating non-malignant hematological disorders in kids.

Participant Groups

Group I: TCR alpha beta T cell depletion Experimental Treatment 1 Intervention

The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol

TCR Alpha Beta T-cell Depleted Haploidentical HCT is already approved in European Union, United States for the following indications:

Approved in European Union as TCRαβ/CD19-depleted haplo-HSCT for:

• Primary immunodeficiencies
• Inherited bone marrow failure syndromes
• Red blood cell disorders
• Metabolic diseases

Approved in United States as TCR Alpha Beta T-cell Depleted Haploidentical HCT for:

• Non-malignant hematological disorders in children
• Primary immunodeficiencies
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Johns Hopkins All Children's Hospital

Lead Sponsor

Trials

47

Recruited

5,009,000+

Findings from Research

In a study of 159 children with leukemia undergoing T-cell depleted haploidentical transplantation, there were no significant differences in transplant outcomes between the two techniques (CD3+/CD19+ vs TCRαβ+/CD19+), indicating that both methods are equally effective.

Key factors influencing better disease-free survival included early disease status at transplant, presence of chronic graft-versus-host disease (cGvHD), and donor KIR-B genotype, rather than the specific T-cell depletion platform used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms. Gonzalez-Vicent, M., Molina, B., Lopez, I., et al.[2022]

Haploidentical stem cell transplantation is becoming a viable option for patients without matched donors, allowing for a broader range of potential donors.

Selective depletion of specific T cells and B cells before transplantation helps reduce the risk of complications like graft-versus-host disease while preserving important immune cells for effective engraftment and anti-tumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR αβ+/CD19+ cell depletion in haploidentical hematopoietic allogeneic stem cell transplantation: a review of current data. Sahasrabudhe, K., Otto, M., Hematti, P., et al.[2020]

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]

In a study of 18 pediatric patients with high-risk malignancies, using total body irradiation (TBI) as a conditioning regimen for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) resulted in successful engraftment in all patients, compared to a high rate of graft rejection (75%) with a reduced-toxicity chemotherapy regimen.

Patients conditioned with TBI showed significantly better overall survival (66% vs. 37%) and event-free survival (61% vs. 33%) compared to those who received chemotherapy, indicating that TBI is a more effective approach for this type of transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two cytoreductive regimens for αβ-T-cell-depleted haploidentical HSCT in pediatric malignancies: Improved engraftment and outcome with TBI-based regimen. Jacoby, E., Varda-Bloom, N., Goldstein, G., et al.[2017]

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]

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]

A multicenter phase I/II trial involving 60 patients showed that haploidentical hematopoietic stem cell transplantation (HSCT) using TCRαβ/CD19-depleted grafts is a safe and effective treatment option, with no cases of severe acute graft-versus-host disease (GVHD) and only 10% experiencing mild GVHD.

With a median follow-up of 733 days, the overall survival rate was 63% and the disease-free survival rate was 50% at 2 years, indicating promising outcomes for patients with various high-risk conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients. Bethge, WA., Eyrich, M., Mielke, S., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms. [2022]

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

TCR αβ+/CD19+ cell depletion in haploidentical hematopoietic allogeneic stem cell transplantation: a review of current data. [2020]

3. 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]

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

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

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

Comparison of two cytoreductive regimens for αβ-T-cell-depleted haploidentical HSCT in pediatric malignancies: Improved engraftment and outcome with TBI-based regimen. [2017]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients. [2022]