Haploidentical Stem Cell Transplant for Blood Diseases

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new type of stem cell transplant to determine its safety and effectiveness in treating certain blood diseases. The treatment, called TCR Alpha Beta T-cell Depleted Haploidentical HCT, uses stem cells from a half-matched family member, such as a parent, which are specially processed. Individuals with severe sickle cell disease, thalassemia, or specific bone marrow failure syndromes who have not responded to standard treatments might be suitable candidates. The trial aims to offer new hope for those facing these challenging conditions. 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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that TCR Alpha Beta T-cell Depleted Haploidentical Stem Cell Transplant (HSCT) is generally safe. Studies have found low rates of deaths unrelated to disease recurrence, meaning fewer patients die from other causes. Additionally, there are low rates of graft-versus-host disease (GVHD), a serious complication where donor cells attack the patient's body.

Importantly, this treatment has been used successfully in children with various blood disorders, indicating its general safety. While researchers continue to study this treatment, these findings offer encouragement for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard blood disease treatments that typically rely on fully matched donor stem cell transplants, TCR Alpha Beta T-cell Depleted Haploidentical HCT offers a novel approach by allowing partially matched family members to be donors. This treatment uses a unique method called TCR alpha beta T cell depletion, which removes specific immune cells that could cause complications, like graft-versus-host disease. Researchers are excited because this approach could make stem cell transplants accessible to more patients, potentially reducing wait times and increasing success rates for those who lack a full match.

What evidence suggests that this TCR Alpha Beta T-cell Depleted Haploidentical HCT is effective for blood diseases?

Research has shown that a special type of stem cell transplant, the TCR Alpha Beta T-cell Depleted Haploidentical HCT, can effectively treat certain blood disorders. In previous studies, children who received this treatment demonstrated high survival rates, with about 91.4% living for at least five years and 86.8% remaining disease-free. These results suggest promise for treating serious conditions. In this trial, participants will receive stem cells from a partially matched family member. The stem cells undergo special processing to remove certain cells, reducing complications and improving outcomes. ^{3 5 6 7 8}

Who Is on the Research Team?

Deepak Chellapandian, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34592755/

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical ... TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment of children with NMDs.

2. ashpublications.org ashpublications.org/bloodadvances/article/6/1/281/477111/TCR-CD19-depleted-HSCT-from-an-HLA-haploidentical

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical ... With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In ...

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

Comprehensive up-to-date analysis on TCRαβ/CD19 ... The clinical efficacy of TCRαβ/CD19-depleted HSCT is underscored by the encouraging outcomes data. Our meta-analysis demonstrated that haplo-HSCT provides a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05288595

TCR Alpha/Beta and CD19-deplete Haplo-HSCT This is a single-site, open label, interventional, non-randomized, phase II trial of TCRαβ/CD19 deplete allogeneic HCT as donor source and sole ...

5. nature.com nature.com/articles/s41409-021-01551-z

Results of a multicenter phase I/II trial of TCRαβ and CD19 ... Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8753220/

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical ... Key Points. TCRαβ/CD19-depleted HLA-haploidentical HSCT is an effective strategy for children with several nonmalignant disorders.

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

TCRαβ/CD19 cell–depleted HLA-haploidentical ... TCRαβ/CD19 cell–depleted haploHSCT is characterized by low NRM and acute/chronic GVHD, with OS and DFS similar to other transplants.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05968170

TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide range of diagnoses including hematologic malignancies, bone marrow ...