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

Recruiting at 1 trial location

Overseen By Jessenia C Campos, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: HIV, Active psychiatric disorder, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

70 Participants Needed

Trial Summary

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that ongoing therapy for the underlying disease may continue if it's in your best interest, according to the clinical judgment of the principal investigator.

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 data supports the effectiveness of the treatment Allogeneic HSC, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Bone Marrow Transplantation, Allogeneic Stem Cell Transplantation for T-Cell Immunodeficiency Disorders?

Research shows that allogeneic hematopoietic stem cell transplantation can be curative for various immunodeficiencies, including T-cell immunodeficiencies, especially when using matched donors. Even when a perfect donor match isn't available, alternative donor strategies have been successful, improving outcomes 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 blood or bone marrow transplant generally safe for humans?

Allogeneic blood or bone marrow transplants can be risky, with significant complications like delayed immune recovery and graft-versus-host disease (GVHD), which is when the donor's immune cells attack the recipient's body. These risks can lead to serious health issues and even death, so careful consideration and expert guidance are essential. ^{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}

How is the treatment Allogeneic HSC different from other treatments for T-cell immunodeficiency disorders?

Allogeneic HSC transplantation is unique because it involves transferring healthy stem cells from a donor to a patient to rebuild their immune system, which can be curative for severe T-cell immunodeficiencies. This treatment is particularly useful when a matched donor is not available, as it can use alternative donor sources, but it requires careful management to prevent complications like graft-versus-host disease. ^{1 2 3 4 10}

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...

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Conditioning

Participants receive chemotherapy and antibody therapy for 2 weeks to prepare for transplantation

2 weeks

Daily hospital visits

Transplantation

Participants receive donor stem cells via catheter and stay in the hospital for several weeks

3-4 weeks

Continuous hospital stay

Follow-up

Participants are monitored for safety and effectiveness after transplantation

1 year

Multiple follow-up visits

Treatment Details

Interventions

• Allogeneic HSC

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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 36 survivors of severe T-lymphocyte immunodeficiencies who underwent hematopoietic stem cell transplantation, those treated with anti-CD52 antibodies showed better long-term immune reconstitution, including higher rates of full donor myeloid chimerism and more robust B-lymphocyte function.

Both treatment methods resulted in good T-lymphocyte function and low incidence of graft-versus-host disease, but anti-CD34-treated patients had more incomplete donor chimerism and less effective B-lymphocyte responses.

NCBI (Pubmed)

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. Slatter, MA., Brigham, K., Dickinson, AM., et al.[2017]

In a study involving 23 allogeneic donors and their transplant recipients, higher CD26 expression in donor cells was significantly associated with increased risk of acute graft-versus-host disease (GVHD) and improved white blood cell (WBC) engraftment.

The results suggest that measuring CD26 expression in donor cells could serve as a potential predictor for acute GVHD, highlighting the need for further research in this area.

NCBI (Pubmed)

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. Punatar, S., Kandekar, S., Khattry, N., et al.[2022]

Allogeneic hematopoietic stem cell transplantation is an effective curative treatment for various primary immunodeficiencies, including both well-known and newly identified conditions.

The article highlights the challenges in establishing a universal transplant regimen due to the rarity and diverse pathophysiology of these immunodeficiencies, emphasizing the need for tailored approaches in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation for primary immunodeficiencies. Kang, E., Gennery, A.[2019]

In a study involving 25 children with primary immunodeficiencies, haploidentical or mismatched unrelated donor hematopoietic stem cell transplantation (HSCT) after depleting TCRαβ CD3+ cells resulted in an impressive overall survival rate of 83.9% and an event-free survival rate of 80.4% at a median follow-up of 20.8 months.

The approach significantly reduced the incidence of acute graft-versus-host disease (GvHD) to 22%, with no cases of chronic GvHD observed, highlighting the safety and efficacy of this transplantation strategy for treating PIDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. Shah, RM., Elfeky, R., Nademi, Z., et al.[2022]

In a study of 44 patients with severe combined immunodeficiency (SCID) who underwent hematopoietic stem cell transplantation (HSCT), most patients showed normal immune reconstitution, with over 90% achieving normal CD3 counts and 72.7% able to stop intravenous immunoglobulin (IVIG) therapy after HSCT.

Bone marrow transplantation resulted in significantly lower rates of acute graft-versus-host disease (GVHD) compared to peripheral stem cell transplantation, suggesting that bone marrow may be the preferred source for HSCT in SCID patients.

NCBI (Pubmed)

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. Demirtas, D., Cagdas, D., Turul Ozgur, T., et al.[2022]

Allogeneic hematopoietic stem cell transplantation (HSCT) has the potential to cure severe autoimmune diseases by replacing a diseased immune system with a healthy one, although it carries higher risks compared to autologous HSCT, including complications and mortality.

Despite the risks, allogeneic HSCT may lead to sustained remissions in selected cases, as evidenced by outcomes in conditions like aplastic anemia and chronic myelogenous leukemia, and initial experiences in patients with systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. Nash, RA.[2007]

Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially replace a diseased immune system with healthy donor cells, showing promise in treating conditions like severe aplastic anemia and autoimmune diseases, but results can vary widely with both complete remissions and treatment failures reported.

Despite its potential benefits, allogeneic HSCT is associated with significant risks, including morbidity and mortality, leading to the conclusion that it cannot be generally recommended without further carefully conducted studies to identify the best patient populations and treatment technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. Gratwohl, A.[2009]

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) with sibling donors experience a complex mix of emotions, feeling both secure in their donor's support and burdened by a sense of responsibility for the donor's safety.

The study highlights the need for healthcare providers to understand the emotional challenges faced by patients and their sibling donors, as this can impact their care and overall experience during the transplantation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. Kisch, A., Bolmsjö, I., Lenhoff, S., et al.[2022]

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective curative treatment for various hematological and genetic diseases, but it can lead to both early and late complications.

A case study of a 49-year-old patient with acute myeloid leukemia (AML) highlighted the occurrence of acute graft versus host disease (GvHD) and late complications such as chronic GvHD, infections, cataracts, and secondary malignancies, emphasizing the need for awareness and education regarding these risks post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report. Trajkovska, I., Georgievski, B., Cevreska, L., et al.[2020]

Umbilical cord blood is a promising alternative stem-cell source for children with severe primary T-cell immunodeficiencies, showing rapid and reliable recovery of immune function after transplantation in a study of 6 children.

The transplantation resulted in low rates of graft-versus-host disease (GvHD) and effective immune reconstitution, with stable development of T-cells, B-cells, and natural killer cells, indicating its safety and efficacy compared to other donor sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. Knutsen, AP., Wall, DA.[2019]

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]

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]

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

Hematopoietic stem cell transplantation for primary immunodeficiencies. [2019]

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]

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]

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

Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. [2007]

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

Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. [2009]

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

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. [2022]

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

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report. [2020]

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]