48 Participants Needed

TCD HCT for Fanconi Anemia

LB
MM
Overseen ByMargaret MacMillan, MD, Msc, FRCPC
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: Masonic Cancer Center, University of Minnesota
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.

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 T Cell Receptor α/β TCD HCT for Fanconi Anemia?

A study involving 24 patients with Fanconi Anemia showed that using TCRαβ+/CD19+-depleted stem cell transplantation led to successful engraftment in 91.6% of patients, with high survival rates and low incidence of severe complications. This suggests that the treatment is effective in achieving stable blood cell production and reducing complications in these patients.12345

Is T Cell Receptor α/β TCD HCT generally safe for humans?

There is no specific safety data available for T Cell Receptor α/β TCD HCT in the provided research articles.678910

What makes the T Cell Receptor α/β TCD HCT treatment unique for Fanconi Anemia?

The T Cell Receptor α/β TCD HCT treatment is unique because it involves the selective depletion of α/β T cells, which can reduce the risk of graft-versus-host disease (a condition where the donor cells attack the recipient's body) while preserving other immune cells that can help fight infections and support recovery.1011121314

Research Team

Margaret MacMillan | Masonic Cancer Center

Margaret MacMillan, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for patients with Fanconi anemia who have a suitable donor for blood cell transplant, are under 65 years old, and have good heart and lung function. They must not be pregnant or breastfeeding, have had solid tumor cancer in the last 2 years, or active infections. Participants need to agree to use contraception during treatment.

Inclusion Criteria

I am under 65 years old.
I have severe anemia, MDS, acute leukemia, or a high-risk genotype.
My liver, heart, and lung functions meet the required health standards.
See 5 more

Exclusion Criteria

I am not pregnant or breastfeeding and have a negative pregnancy test.
I have not had an uncontrolled infection in the last week.
I was diagnosed with a solid tumor cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell transplantation

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Monitoring for chronic graft versus host disease and overall survival

1 year

Treatment Details

Interventions

  • T Cell Receptor α/β TCD HCT
Trial Overview The study tests T cell receptor α/β depletion (α/β TCD) hematopoietic cell transplantation (HCT) in Fanconi anemia patients. It aims to reduce graft-versus-host disease without routine immune suppression drugs, hoping for faster immune recovery and fewer severe infections post-transplant.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.Experimental Treatment4 Interventions
given to TBD patients with: * Early MDS features (with or without cytogenetic abnormalities) AND * Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.
Group II: Treatment Plan 4: CY, FLU, and alemtuzumabExperimental Treatment3 Interventions
given to TBD patients with: * Bone marrow failure AND * Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 3 patients would be treated per year. Statistical outcomes will be descriptive.
Group III: Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi AnemiaExperimental Treatment5 Interventions
Given to: * Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI * Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia who cannot tolerate TBI * Per treating physician preference
Group IV: Treatment Plan 2: CY, FLU and MP in patients with Fanconi AnemiaExperimental Treatment6 Interventions
Given to: • HLA-identical sibling donor recipients with aplastic anemia
Group V: Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP in patients with Fanconi AnemiaExperimental Treatment7 Interventions
Given to: * Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR * Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia

T Cell Receptor α/β TCD HCT is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as α/β TCD HCT for:
  • Inherited Bone Marrow Failure Disorders
  • Fanconi Anemia
  • Primary Immunodeficiency Diseases
🇺🇸
Approved in United States as α/β TCD HCT for:
  • Inherited Bone Marrow Failure Disorders
  • Fanconi Anemia
  • Primary Immunodeficiency Diseases
  • Nonmalignant Diseases

Find a Clinic Near You

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials
285
Recruited
15,700+

Findings from Research

γ/δ T cells, which make up 2-10% of T cells in human blood, have shown potential as beneficial effector cells in hematopoietic stem cell transplantation (HSCT), suggesting they could improve outcomes in allogeneic transplants.
Depleting α/β T lymphocytes from grafts can lower the risk of graft-versus-host disease (GvHD) while preserving γ/δ T cells and other beneficial cells, which may enhance engraftment and reduce infection risks.
Transplantation in the onco-hematology field: focus on the manipulation of αβ and γδ T cells.Daniele, N., Scerpa, MC., Caniglia, M., et al.[2012]
In a study of 23 patients receiving allogeneic stem cell transplants, T cell depletion (TCD) strategies were found to slow the recovery of CD4 T cells, especially in those receiving fully TCD grafts, which persisted for the entire 12-month monitoring period.
Despite the slower recovery of CD4 cells, TCD recipients showed a more rapid recovery of natural killer (NK) cells, indicating that TCD may influence the reconstitution of different immune cell types post-transplant.
The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia.Lowdell, MW., Craston, R., Ray, N., et al.[2017]
In a phase 2 trial involving 24 patients with Fanconi anemia, 91.6% achieved sustained primary engraftment after receiving T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation, with quick recovery times for neutrophils and platelets.
The treatment was well tolerated with no fatal transplant-related toxicities, and after a median follow-up of 5.2 years, the overall survival rate was 100%, indicating high efficacy and safety of this transplantation method.
HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia.Strocchio, L., Pagliara, D., Algeri, M., et al.[2022]

References

Transplantation in the onco-hematology field: focus on the manipulation of αβ and γδ T cells. [2012]
The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia. [2017]
HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. [2022]
Low dose T-cell lymphocyte infusion combined with marrow T-cell depletion as prophylaxis of acute graft vs host disease for HLA identical sibling bone marrow transplantation. [2019]
A new limiting dilution culture system for the detection of T cell subsets in T cell-depleted marrow grafts. [2006]
Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias. [2023]
High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review. [2023]
Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy. [2021]
Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Characterization and modulation of anti-αβTCR antibodies and their respective binding sites at the βTCR chain to enrich engineered T cells. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
T-cell receptor beta usage by 35 different antigen-specific T-cell clones restricted by HLA-Dw4 or -Dw14.1. [2019]
13.United Statespubmed.ncbi.nlm.nih.gov
Defective interactions between TCR chains and CD3 heterodimers prevent membrane expression of TCR-alpha beta in human T cells. [2017]
14.United Statespubmed.ncbi.nlm.nih.gov
The molecular bases of δ/αβ T cell-mediated antigen recognition. [2022]
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