Allogeneic Blood or Bone Marrow Transplant for T-Cell Immunodeficiency Disorders

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Dimana Dimitrova, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Background: Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems. Eligibility: Donors: Healthy people ages 4 and older Recipients: People the same age with abnormal T-cell function causing health problems Design: All participants will be screened with: * Medical history * Physical exam * Blood, heart, and urine tests Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test. Recipients will also have lung tests. Some participants will have scans and/or bone marrow collected by needle in the hip bones. Donors will learn about medicines and activities to avoid and repeat some screening tests. Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia. Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm. Recipients will have: * More bone marrow and a small fragment of bone removed * Dental, diet, and social worker consultations * Scans * Chemotherapy and antibody therapy for 2 weeks * Catheter inserted in a chest or neck vein to receive donor stem cells * A hospital stay for several weeks with more medicines and procedures * Multiple follow-up visits

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are receiving standard therapy for your underlying disorder, you may continue it as a bridge to the transplant. It's best to discuss your specific medications with the trial team.

What data supports the idea that Allogeneic Blood or Bone Marrow Transplant for T-Cell Immunodeficiency Disorders is an effective treatment?

The available research shows that Allogeneic Blood or Bone Marrow Transplant is an effective treatment for T-Cell Immunodeficiency Disorders. It has been shown to be curative for both well-known and newly discovered immunodeficiencies. The treatment is especially successful when a matched donor is available, but even when a perfect match isn't possible, using a partially matched donor can still be beneficial. This treatment is preferred for several immune disorders because it can restore the immune system's function, which is crucial for patients with these conditions. ^{1 2 3 4 5}

What safety data is available for allogeneic blood or bone marrow transplant in T-cell immunodeficiency disorders?

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with significant risks, including delayed immune reconstitution and graft-versus-host disease (GVHD). The treatment has been studied in various conditions, such as autoimmune diseases, aplastic anemia, and chronic myelogenous leukemia, showing potential for sustained remissions but also significant morbidity and mortality. Early complications occur within the first 100 days, while late complications arise after 100 days post-transplant. The risks may outweigh the benefits, and careful prospective studies are needed to better define target populations and optimize the technology used. ^{2 6 7 8 9}

Is Allogeneic HSC a promising treatment for T-Cell Immunodeficiency Disorders?

Yes, Allogeneic HSC is a promising treatment for T-Cell Immunodeficiency Disorders. It has been shown to be effective in curing these disorders, especially when a matched donor is available. Even when a perfect match isn't possible, alternative donor options can still lead to successful outcomes. This treatment helps rebuild the immune system, which is crucial for patients with severe T-cell immunodeficiencies. ^{1 2 3 4 10}

Research Team

Dimana Dimitrova, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for people aged 4 and older with T-cell disorders, such as immune deficiencies or lymphoproliferative diseases. Participants must have certain medical conditions like abnormal T-cell function or specific genetic mutations affecting the immune system. They need to be in a stable condition to undergo transplant procedures and agree to use contraception if of childbearing potential.

Inclusion Criteria

I am at least 4 years old.

My organs are enlarged or not working well due to T-cell infiltration.

I have a latent herpesvirus infection in my T cells.

Exclusion Criteria

You cannot participate if you are currently taking any experimental drugs, except for virus-specific cytotoxic T-cells used to treat viral infections prior to a certain type of transplant.

Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol or which does not allow for appropriate informed consent

HIV positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of TCP/D severity and/or the attribution of clinical manifestations of immunodeficiency to a disorder of TCP/D.

Treatment Details

Interventions

• Allogeneic HSC (Cell Therapy)

Trial Overview The study tests whether transferring healthy blood stem cells from one person (donor) to another (recipient) can effectively treat various T-cell related health issues. It involves screening, preparation including chemotherapy, receiving donor stem cells through a catheter, and follow-up visits.

Participant Groups

Group I: 2/IOC Arm Experimental Treatment 3 Interventions

Immunosuppression Only Conditioning Arm

Group II: 1/RIC Arm Experimental Treatment 3 Interventions

Reduced Intensity Conditioning Arm

Group III: 3/donor arm Active Control 1 Intervention

Healthy Donor- Donors for recipients in arm 1 or arm 2

Allogeneic HSC is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Allogeneic Hematopoietic Cell Transplantation for:

• Acute leukemia
• Chronic leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Multiple myeloma
• Myelodysplastic syndromes
• Myeloproliferative neoplasms

🇺🇸 Approved in United States as Allogeneic Hematopoietic Cell Transplantation for:

• Acute myeloid leukemia
• Acute lymphoblastic leukemia
• Chronic myeloid leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Multiple myeloma
• Myelodysplastic syndromes
• Myeloproliferative neoplasms

🇨🇦 Approved in Canada as Allogeneic Hematopoietic Cell Transplantation for:

• Acute leukemia
• Chronic leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Multiple myeloma
• Myelodysplastic syndromes
• Myeloproliferative neoplasms

🇯🇵 Approved in Japan as Allogeneic Hematopoietic Cell Transplantation for:

• Acute myeloid leukemia
• Acute lymphoblastic leukemia
• Chronic myeloid leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Multiple myeloma
• Myelodysplastic syndromes
• Myeloproliferative neoplasms

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

National Marrow Donor Program Minneapolis, MN

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14080

Patients Recruited

41,180,000+

References

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

Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency. [2017] Results of treatment of severe T-lymphocyte immunodeficiencies by means of hematopoietic stem cell (HSC) transplantation have improved. T cell-depleted haploidentical transplantations are successful if there is no HLA-identical donor. Methods to remove T lymphocytes include addition of anti-CD52 antibodies and CD34(+) HSC selection.

2. Netherlands pubmed.ncbi.nlm.nih.gov

CD26 expression on donor harvest as a risk predictive biomarker for developing graft-versus-host disease post-allogeneic hematopoietic stem cell transplantation: A ten-year follow-up study. [2022] Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft-versus-host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long-term transplant outcomes.

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

Hematopoietic stem cell transplantation for primary immunodeficiencies. [2019] Allogeneic hematopoietic stem cell transplantation has been shown to be curative for well-described as well as newly discovered immunodeficiencies. However, it is difficulty to define a universal transplant regimen given the rarity of these disorders and the varied pathophysiology these disorders encompass. This article discusses those primary immunodeficiencies most commonly treated by hematopoietic stem cell transplant and describes the transplant issues specific to these disorders.

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

T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. [2022] Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants.

5. England pubmed.ncbi.nlm.nih.gov

Long Term Follow-Up of the Patients with Severe Combined Immunodeficiency After Hematopoietic Stem Cell Transplantation: A Single-Center Study. [2022] We aimed to evaluate hematopoietic stem cell transplantation (HSCT) related outcomes of patients with severe combined immunodeficiency (SCID).

6. England pubmed.ncbi.nlm.nih.gov

Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. [2007] Allogeneic hematopoietic stem cell transplantation (HSCT) tests the hypothesis that the replacement of a 'diseased' autoreactive immunological and stem cell compartment with one that is not autoreactive (but potentially alloreactive) can cure severe autoimmune diseases. The primary risks of allogeneic HSCT are the morbidity and morality associated with delayed immune reconstitution and GVHD. Although the risk of complications and mortality is greater than autologous HSCT, studies of allogeneic HSCT should be conducted in selected cases because there is a greater potential for sustained remissions. This review will discuss the anticipated results from allogeneic HSCT by summarizing outcomes in aplastic anemia and chronic myelogenous leukemia as well as a brief description of Seattle's experience with allogeneic HSCT in the first two patients with systemic sclerosis.

7. England pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. [2009] Allogeneic hematopoietic stem cell transplantation (HSCT) offers the unique opportunity to replace a diseased hematopoietic or immune system by healthy donor cells. Proof of principle comes from experimental animal data, from the experience with severe aplastic anemia, from observations of patients with concomitant autoimmune disease and from scattered case reports. Complete remissions have been described as well as failures. Allogeneic HSCT remains associated with significant morbidity and mortality. The potential risks might outweight the benefits. Currently, allogeneic HSCT cannot be recommended in general. Carefully conducted prospective studies are warranted to define target populations and best technology to be used. Conditions for such studies have been identified by an international expert panel.

8. Scotland pubmed.ncbi.nlm.nih.gov

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. [2022] Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor.

9. North Macedonia pubmed.ncbi.nlm.nih.gov

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report. [2020] Allogeneic hematopoietic stem cells transplantation (HSCT) is a curative intervention in patients with haematological malignant and non-malignant diseases, immunodeficiency, autoimmune, and other genetic diseases. Early complications are complications that are occurring in the first 100 days, while complications arising after the 100th day of transplantation belong to late complications.

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

Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. [2019] Hematopoietic stem-cell transplantation is the treatment of choice for severe primary T-cell immunodeficiencies. When an HLA-identical sibling donor is not available, an alternative donor stem-cell source is needed. In primary T-cell immunodeficiencies, T-cell-depleted HLA-haploidentical bone marrow transplantation has been particularly successful in reconstituting the T-cell immune system in many of the severe combined immunodeficiency syndrome types. However, there are some problems associated with this preparation as a stem donor source, such as increased resistance to engraftment, a long period of time for T-cell engraftment to occur, and failure to engraft B cells and B-cell functions. These problems can be especially troublesome if the patient is infected before the transplantation.