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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called allogeneic blood or bone marrow transplant for individuals with T-cell immunodeficiency disorders. Researchers aim to determine if this method can safely provide a new, healthy immune system to address issues caused by abnormal T-cells, which are crucial for fighting infections. The trial includes two main treatment paths: one involves reduced-intensity conditioning (a less intense pre-treatment), and the other uses only immunosuppression (medications to lower immune activity). This study is suitable for individuals with T-cell-related health problems, such as frequent or prolonged fevers due to immune issues, who have a related or unrelated donor match. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

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.

Is there any evidence suggesting that allogeneic blood or bone marrow transplant is likely to be safe for humans?

Research has shown that using blood stem cells from a donor, known as allogeneic hematopoietic stem cell (HSC) transplants, can safely treat T-cell issues. When a gentler approach called reduced intensity conditioning (RIC) is used, studies have found it to be well-tolerated by patients with conditions like certain blood cancers. This approach is easier on the body, making it safer for those who might not handle stronger treatments well.

For those receiving the transplant with only immunosuppression, evidence also suggests safety. These transplants replace faulty immune cells with healthy ones from the donor. Studies report promising survival rates and manageable side effects.

While all treatments carry risks, these findings offer encouragement for those considering this type of transplant. The goal is to provide a new, healthy immune system with fewer complications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using allogeneic hematopoietic stem cell (HSC) transplants for T-cell immunodeficiency disorders because these transplants offer the potential for a long-term solution by replacing faulty immune cells with healthy ones from a donor. Unlike traditional treatments that mainly focus on managing symptoms or boosting the immune system temporarily, this approach aims to correct the underlying immune deficiency. The trial explores two innovative conditioning methods: Reduced Intensity Conditioning (RIC), which lessens the harsh side effects often associated with transplants, and Immunosuppression Only Conditioning (IOC), which could make the procedure safer for more patients. These methods could make transplants more accessible and tolerable, offering hope for a more permanent fix to these challenging disorders.

What evidence suggests that this trial's treatments could be effective for T-cell immunodeficiency disorders?

Research has shown that allogeneic hematopoietic stem cell transplants (allo-HSCT) can effectively replace faulty immune systems in people with T-cell disorders. Studies have found that this treatment leads to high survival rates. For example, about 88.9% of patients with rare immune deficiencies survived three years after the transplant. Another study showed a 76% survival rate when the donor was a close match. This trial will compare different conditioning regimens for allo-HSCT, including a Reduced Intensity Conditioning Arm and an Immunosuppression Only Conditioning Arm. The treatment works by giving patients new stem cells, which can grow into healthy immune cells and fix the T-cell problem. These findings suggest that allo-HSCT is a promising option for improving the health of people with T-cell immunodeficiencies. ^{2 3 6 7 8}

Who Is on the Research Team?

Dimana Dimitrova, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 (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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3357108/

Allogeneic Hematopoietic Cell Transplantation for Primary ... Nearly 750 children with SCID have been transplanted, and over 500 are alive. Among 250 patients with WAS who received HCT, nearly 200 are alive; similarly, 46 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6225386/

Successful outcome following allogeneic hematopoietic ... The rarer PID patients without chronic granulomatous disease (CGD) achieved an OS at 3 years of 88.9% (n = 18), compared with 81.8% for CGD patients (n = 11).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Allo-HSCT in SCD has OS, EFS, and mortality rates of 94%, 86% and 6%, respectively. •. NMA conditioning has the lowest aGVHD, cGVHD, and ...

4. ashpublications.org ashpublications.org/hematology/article/2020/1/649/474361/Allogeneic-hematopoietic-stem-cell-transplantation

Allogeneic hematopoietic stem cell transplantation in adults ... Allo-HSCT allows the replacement of defective or dysregulated recipient immune and hematopoietic cells with long-term repopulating cells from a ...

5. aetna.com aetna.com/cpb/medical/data/800_899/0830.html

Hematopoietic Cell Transplantation for Primary ... Survival was 76% in phenoidentical transplants (n = 23) and 46% (n = 47) in mismatched related donor transplants. The authors concluded that individual disease ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2943393/

Allogeneic hematopoietic cell transplantation: the state of ... Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of malignant and non-malignant conditions.

7. astctjournal.org astctjournal.org/article/S1083-8791(19)30204-6/fulltext

Risks and Outcomes of Allogeneic Hematopoietic Stem ... Twenty-four patients were alive in complete remission on long-term follow-up, with 25 deaths reported. Fifteen deaths (60%) occurred due to relapse, including 3 ...

8. nature.com nature.com/articles/s41409-022-01739-x

Curative allogeneic hematopoietic stem cell transplantation ... Overall survival (OS) was 80.4% (100% for CGD and 74% for other PID patients) at 9 months and beyond (median follow-up 51.6 months). Six ...