Stem Cell Transplant for Immune Deficiency Syndrome

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Dennis D Hickstein, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B, Psychiatric disorder, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Background: - GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells. Objectives: - To see if stem cell transplants are successful at treating GATA2 mutations and related conditions. Eligibility: - Recipients who are between 8 and 70 years of age and have GATA2 deficiency. Design: * All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests. * Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells. * Recipients will stay in the hospital until their condition is stable after transplant. * Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time.

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.

What data supports the effectiveness of the treatment Allogeneic HSCT for Immune Deficiency Syndrome?

Research shows that allogeneic hematopoietic stem cell transplantation (HSCT) can cure many primary immune deficiency disorders, such as Severe Combined Immunodeficiency (SCID), by replacing faulty immune cells with healthy ones from a donor. This treatment has been used successfully for various inherited immune disorders, although challenges like matching donor compatibility remain.

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Is allogeneic hematopoietic stem cell transplantation (HSCT) generally safe for humans?

Allogeneic hematopoietic stem cell transplantation (HSCT) has been used for over 30 years and is generally considered safe, though it does come with risks. The main concerns are related to anesthesia during the procedure and potential complications like graft-versus-host disease (GVHD), which can cause significant health issues. However, serious adverse events are rare, and the procedure is closely monitored to ensure donor and patient safety.

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How is the treatment Allogeneic HSCT different from other treatments for immune deficiency syndrome?

Allogeneic HSCT is unique because it involves transplanting stem cells from a donor to replace the patient's faulty immune system, offering a potential cure for immune deficiency syndromes. Unlike other treatments that may only manage symptoms, this approach aims to reconstitute the immune system, especially when a matched donor is available, although it can be complex due to compatibility issues.

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Eligibility Criteria

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

Trial Timeline

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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Deficiencies and Bone Marrow Failure Syndromes. [2022] Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS).

2. France pubmed.ncbi.nlm.nih.gov

[Cell therapy for inherited diseases of the hematopoietic system]. [2007] Cell therapy was born in 1968 with the first allogeneic transplantation of hematopoietic stem cells for two immune deficiency disorders: the Wiskott-Aldrich syndrome and the Severe Combined ImmunoDeficiency (SCID). From this pioneering experience, thousands of patients affected with inherited or acquired diseases of the hematopoietic system have benefited from this therapeutic approach. Unfortunately, immunologic obstacles, represented by the compatibility in the major histocompatibility HLA system, still dictate today important limitations for a larger therapeutic utilization of hematopoietic stem cells (HSC). In this review, we have summarized the difficulties and the scientific advances leading us to improve the clinical results; the therapeutic research's track for primary immunodeficiencies is also discussed.

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. 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).

5. England 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. [2021] Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.

6. 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.

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

Safety of bone marrow stem cell donation: a review. [2010] Allogeneic hematopoietic stem cell transplantation (HSCT) represents the first choice of treatment or an important therapeutic option for several diseases, but it is still marked by morbidity and mortality. In contrast, the donation of hematopoietic stem cells (HSCs) is considered to be a safe procedure. The invaluable ethical source of donation and its central role in transplantation implies that the greatest attention be due to the donor and to the donation process through a serious monitoring protocol for donor safety. Both the Joint Accreditation Committee and the European Committee pay particular attention to the notification of adverse events and adverse reactions. Bone marrow donation is a well established procedure, that has now been performed for >30 years. Although it does not require drug administration, there is hospital admission for 1-3 days with 7-10 days off work. The main risk is related to the anesthesia. Pain in the aspiration area, together with astenia are considered to be the most frequent side effects, as shown by the USA National Marrow Donor Program experience in 1,193 donations. In the European Group for Blood and Marrow Transplantation analysis performed between 1993 and 2005 on 27,770 first HSCTs from bone marrow, only 1 fatal event (pulmonary embolism) and 12 serious adverse events were observed. The most frequent adverse events were cardiac. The incidence of adverse events was significantly lower (P

8. 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.

9. 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.

10. Switzerland pubmed.ncbi.nlm.nih.gov

The use of HLA-non-identical T-cell-depleted marrow transplants for correction of severe combined immunodeficiency disease. [2008] Since the introduction of methods for depleting T lymphocytes from human allogeneic marrow grafts in 1980, such transplants have been increasingly used as a source of lymphoid progenitors for the curative treatment of patients with lethal genetic disorders of immunity who lack an HLA matched sibling donor. This review of the results of HLA-haplotype disparate T-cell depleted marrow grafts applied to the treatment of severe combined immunodeficiency (SCID) indicates that such transplants can lead to durable engraftment and successful reconstitution of immune function without severe graft vs. host disease in a high proportion of cases. Resistance to engraftment and selective abnormalities of B cell development and function in the post transplant period constitute major obstacles to the success of these transplants. However, considerable progress has been made towards the elucidation of the cellular mechanisms responsible for graft resistance, graft-host tolerance and either the full or limited immunologic reconstitutions achieved.

11. 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.

12. 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.