Stem Cell Transplant for Immune Deficiency Syndrome

Recruiting at 1 trial location

Overseen By Danielle E Pregent-Arnold, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B, 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: 2

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether stem cell transplants can effectively treat individuals with GATA2 deficiency, a genetic condition that can cause severe immune problems and even leukemia. The trial involves receiving healthy stem cells from a donor to help the body produce strong bone marrow and blood cells, potentially combating the disease. This procedure, known as Allogeneic Hematopoietic Stem Cell Transplant (Allogeneic HSCT), is suitable for individuals aged 6 to 70 diagnosed with GATA2 deficiency who have experienced serious infections or immune issues. Participants will undergo a series of treatments and assessments, including chemotherapy or radiation, followed by the stem cell transplant, and will need to remain under close medical supervision for a period. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since participants will undergo chemotherapy or radiation before the transplant, it's possible that some medications might need to be adjusted. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using donor stem cells for transplants is generally safe for individuals with certain immune disorders. Studies have found that this treatment often results in high survival rates. For example, one study reported a 94% survival rate and an 86% rate of living without complications in some cases.

Additionally, past patients have demonstrated that the procedure can be performed with fewer complications when specific preparation methods are used. For instance, certain treatments before the transplant can reduce the risk of graft-versus-host disease, a condition where donor cells attack the recipient’s body.

It's important to note that while many patients do well, there are risks. Some studies have reported that a small percentage of patients may experience serious complications or a recurrence of their condition. However, many patients who survive show no signs of ongoing infection or disease issues after the transplant.

Overall, using donor stem cells has proven to be a well-tolerated treatment for individuals with genetic immune deficiencies, offering a chance for long-term remission and improved quality of life. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for immune deficiency syndromes, which often rely on medications to manage symptoms, the stem cell transplant approach, specifically allogeneic hematopoietic stem cell transplantation (HSCT), aims to address the root cause by rebuilding the immune system. This treatment is unique because it involves transplanting healthy stem cells from a matched donor, potentially offering a long-term solution by regenerating a functional immune system. Researchers are particularly excited about the possibility of achieving better matches with haploidentical or partially matched donors, which could expand the pool of eligible donors and improve outcomes for more patients. By focusing on the underlying immune system dysfunction, this approach holds promise for a more comprehensive and lasting impact compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for GATA2 deficiency?

Research has shown that stem cell transplants from donors, known as Allo-HSCT, successfully treat severe immune system disorders in both children and adults. In past studies, about 200 adults experienced positive results with this treatment. In this trial, participants will receive Allo-HSCT from different types of donors, depending on their assigned treatment arm. Allo-HSCT replaces a patient's faulty stem cells with healthy ones from a donor, creating new, healthy blood and immune cells. This method has been especially effective in reducing disease complications and has even led some patients to no longer need medication. These findings suggest that stem cell transplants could be a promising treatment for conditions like GATA2 deficiency. ^{3 4 6 7 8}

Who Is on the Research Team?

Danielle E Pregent-Arnold, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for people aged 8-70 with GATA2 deficiency, a genetic condition that can lead to leukemia. Participants need functioning kidneys, liver, heart, and lungs. They must have a matching stem cell donor and agree to use birth control. Excluded are those with active infections or malignancies, pregnant or breastfeeding women, HIV-positive individuals, and anyone allergic to the study drugs.

Inclusion Criteria

Ability to understand and sign a written informed consent document

Left ventricular ejection fraction > 40%

I will have an adult caregiver with me after my transplant.

Exclusion Criteria

History of allergic reactions to specific compounds

History of psychiatric disorder affecting compliance with transplant protocol

Pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-transplant Conditioning

Participants receive chemotherapy or radiation to prepare for the transplant

1 week

Daily visits (in-patient)

Transplant

Participants receive the donated stem cells

1 day

1 visit (in-patient)

Post-transplant Monitoring

Frequent blood tests and scans for the first 6 months, followed by less frequent visits

6 months

Frequent visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic HSCT

Trial Overview The trial tests whether an allogeneic hematopoietic stem cell transplant (HSCT) from a matched donor can treat GATA2 mutations effectively. It involves chemotherapy or radiation before the transplant and requires hospitalization until stable post-transplant followed by regular monitoring.

How Is the Trial Designed?

Group I: Arm A Active Control 6 Interventions

10/10 HLA Matched Related Donor or Unrelated Donor or 9/10 HLA with DQ mismatch Transplant

Group II: Arm B Active Control 7 Interventions

9/10 or 8/10 HLA Match Related Donor or Unrelated Donor or Haploidentical Donor Transplant

Group III: Arm C (combined with Arm B per Amendment N) Active Control 7 Interventions

Haploidentical Related Donor Transplant

Group IV: Arm D (Deleted this arm per amendment I) Active Control 5 Interventions

Umbilical Cord Blood Transplant

Group V: Arm E (Deleted this arm per amendment O) Active Control 1 Intervention

Donor

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

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplant for:

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes
• Primary Immunodeficiency Diseases
• Severe Combined Immunodeficiency
• Sickle Cell Disease
• Thalassemia

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplant for:

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes
• Primary Immunodeficiency Diseases
• Severe Combined Immunodeficiency
• Sickle Cell Disease
• Thalassemia
• Hodgkin Lymphoma
• Non-Hodgkin Lymphoma

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplant for:

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes
• Primary Immunodeficiency Diseases
• Severe Combined Immunodeficiency
• Sickle Cell Disease
• Thalassemia

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplant for:

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes
• Primary Immunodeficiency Diseases
• Severe Combined Immunodeficiency
• Sickle Cell Disease
• Thalassemia

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

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critical treatment option for various diseases, but it carries risks of morbidity and mortality, highlighting the importance of donor safety during the stem cell donation process.

Bone marrow donation is a well-established and generally safe procedure, with a low incidence of serious adverse events (only 1 fatal event reported among 27,770 donations), and the most common side effects being pain and fatigue, indicating that careful donor selection is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bone marrow stem cell donation: a review. Bosi, A., Bartolozzi, B.[2010]

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]

In a study involving 15 patients with severe aplastic anemia (SAA), high-dose allogeneic hematopoietic stem cell transplantation (allo-HSCT) using G-CSF mobilized peripheral blood and bone marrow stem cells from HLA-identical siblings resulted in successful bone marrow engraftment for all patients, with only one case of late rejection.

The treatment showed a promising safety profile, with no acute graft-versus-host disease (GVHD) observed and a low incidence of chronic GVHD at 6.67%, alongside a high three-year disease-free survival rate of 79.8%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia. Sun, ZM., Liu, HL., Geng, LQ., et al.[2021]

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]

Cell therapy began in 1968 with the first successful transplantation of hematopoietic stem cells, which has since helped thousands of patients with immune disorders like Wiskott-Aldrich syndrome and Severe Combined ImmunoDeficiency (SCID).

Despite its success, the effectiveness of hematopoietic stem cell therapy is still limited by immunologic challenges related to HLA compatibility, which poses significant obstacles for broader application in treating various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cell therapy for inherited diseases of the hematopoietic system]. Cavazzana-Calvo, M., Dal-Cortivo, L., André-Schmutz, I., et al.[2007]

HLA-haplotype disparate T-cell depleted marrow grafts can successfully treat severe combined immunodeficiency (SCID), leading to durable immune function reconstitution without severe graft vs. host disease in many cases.

Despite the success, challenges remain, such as resistance to engraftment and issues with B cell development, but ongoing research is uncovering the cellular mechanisms that influence these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of HLA-non-identical T-cell-depleted marrow transplants for correction of severe combined immunodeficiency disease. O'Reilly, RJ., Keever, CA., Small, TN., et al.[2008]

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]

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]

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]

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]

In a study of 25 patients undergoing allogeneic bone marrow transplantation (alloBMT) with reduced intensity conditioning and post-transplantation cyclophosphamide, the 2-year overall survival rate was an impressive 92%, indicating high efficacy of this treatment approach.

The modified protocol resulted in low rates of graft-versus-host disease (GVHD), with only 17% experiencing grade II acute GVHD and 14% chronic GVHD, suggesting that the removal of low-dose TBI and the use of alternative donor sources can enhance safety and reduce complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Deficiencies and Bone Marrow Failure Syndromes. Klein, OR., Bapty, S., Lederman, HM., 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]

Citations

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

Successful outcome following allogeneic hematopoietic ... Children with severe PIDs have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which has been the major therapeutic ...

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

Allogeneic hematopoietic stem cell transplantation in adults ... There is a growing body of publications detailing outcome data on approximately 200 cases of allo-HSCT for PID in adults.4,5,11,17-25 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1542356525004045

Outcomes of Allogeneic Hematopoietic Stem Cell ... HSCT resulted in IBD medication-free remission and reduction in disease-associated complications. This highlights the strength of genetic evaluation in ...

4. astctjournal.org astctjournal.org/article/S2666-6367(21)00800-9/fulltext

Efficacy of Allogeneic Hematopoietic Cell Transplantation ... Allogeneic hematopoietic cell transplantation (HCT) may be efficacious for autoimmune diseases (AIDs), but its efficacy for individual AIDs is unknown.

5. nature.com nature.com/articles/s41409-025-02569-3

Impact of center volume on outcomes in allogeneic ... The impact of center volume on outcomes in pediatric hematopoietic cell transplantation (HCT) is not well established.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11703937/

Pre-Transplant Immune Dysregulation Predicts for Poor ... Allogeneic haematopoietic stem cell transplantation (alloHSCT) is safe and effective for adolescents and adults with inborn errors of immunity ( ...

7. 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 ...

8. 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 ...