Haploidentical Stem Cell Transplant for Blood Diseases

Recruiting in Palo Alto (17 mi)

Overseen by Deepak Chellapandian, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Johns Hopkins All Children's Hospital

Disqualifiers: Pregnancy, HIV, Active infections, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

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.

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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.

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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.

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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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Johns Hopkins All Children's Hospital Saint Petersburg, FL

Who Is Running the Clinical Trial?

Johns Hopkins All Children's Hospital Lead Sponsor

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] T-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCRαβ+/CD19+ depletion techniques has been increasingly used in children with hematological malignancies. We present a retrospective study aimed to compare transplant outcomes in children with leukemia receiving a TCD haploidentical transplant using either CD3+/CD19+ or TCRαβ+/CD19+ platforms.

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] Allogeneic hematopoietic stem cell transplantation is a curative option for patients with a variety of diseases. Transplantation from a related haploidentical donor is being increasingly utilized for patients who lack an available human leukocyte antigen matched related or unrelated donor. 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 transplant. This allows for the removal of cells responsible for graft-versus-host disease and post-transplant lymphoproliferative disorder but maintains hematopoietic progenitor and stem cells for engraftment (CD34+ cells), as well as cells to elicit graft-versus-tumor effect and provide anti-infective activity (such as gamma-delta T cells and natural killer cells). The aim of this review article is to present and discuss the data available to date from studies utilizing this method of transplantation.

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] Haploidntical hematopoietic stem cell transplantation has been increasingly used in recent years for patients without a matched donor. The αβTCR+/CD19+ depletion technique provide a graft that is enriched with CD34 cells, γδ-T-cells and natural killer. The current experience with αβTCR+/CD19+ depleted grafts in pediatric patients with malignant and non-malignant disorders, demonstrated rapid engraftment, improved immune reconstitution and low risk of GVHD. Future studies will need to define the optimal conditioning regimen in order to improve transplant outcome.

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] In vitro or in vivo depletion of alloreactive T cells can facilitate haplo-identical hematopoietic stem cell transplantation (HSCT). Very satisfactory transplant outcomes were thus reported for TCRαβ/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current semi-automatic manufacturing process on the CliniMACS Plus, although robust, still requires a significant amount of manual labor to be completed. Towards advancing and further facilitating large scale cell processing, a new TCRαβ/CD19 depletion module combined with the previously described CD45RA depletion module (to serve as allo-reactivity attenuated donor lymphocyte infusion) was established on the CliniMACS Prodigy.

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] Graft manipulation using selective depletion of αβ-T cells provides a source of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) enriched in effector cells. We report our experience implementing this haplo-HSCT for high-risk malignancies in pediatric patients focusing on the conditioning regimen.

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

TCRαβ/CD19 cell-depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis. [2023] TCRαβ/CD19-cell depletion is a promising graft manipulation technique frequently used in the context of HLA-haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of ex-vivo T cell-depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median value of 47.6 months for surviving patients). With a 5-year cumulative incidence of non-relapse mortality of 5.2% (95% confidence interval, CI, 2.8-8.8) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9-29.2), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI 68.6-80.9) and 71.6% (95% CI 64.4-77.6), respectively. Cumulative incidence of both grade II-IV acute and chronic GvHD were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including also type of disease, use of total body irradiation in the conditioning regimen [hazard ratio (HR) 0.5 (95% CI, 0.26-0.98, p=0.04)], disease status at HSCT [CR>3 versus CR1/2; HR 2.23 (95% CI, 1.20-4.16, p=0.01] and high levels of pre-HSCT minimal residual disease [HR 2.09 (95% CI, 1.01-4.33, p=0.04)] were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable to those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.

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

Generation and flow cytometric quality control of clinical-scale TCRαβ/CD19-depleted grafts. [2017] Label="BACKGROUND">The depletion of TCR&#945;&#946;+ T cells and CD19+ B cells is a graft purification method for haploidentical stem cell transplantation (HSCT) retaining stem cells, NK cells and TCR&#947;&#948;+ T cells. To avoid treatment-related occurrence of severe GvHD a precise quantification of residual TCR&#945;&#946;+ T cells in the graft is of essential importance.

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] Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCR&#945;&#946; and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n&#8201;=&#8201;43), myelodysplastic or myeloproliferative syndrome (n&#8201;=&#8201;6), multiple myeloma (n&#8201;=&#8201;1), solid tumors (n&#8201;=&#8201;6), and non-malignant disorders (n&#8201;=&#8201;4) were enrolled. TCR &#945;&#946;/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1&#8201;&#215;&#8201;106 CD34+ cells/kg and 14.2&#8201;&#215;&#8201;103 TCR&#945;&#946;+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCR&#945;&#946;/CD19-depleted grafts represents a viable treatment option.