Bone Marrow Transplant for Immune Deficiency

Recruiting at 2 trial locations

Overseen By Amy H Chai

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

254 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a bone marrow transplant from a healthy donor can be safe and effective for individuals with primary immunodeficiency, a condition where the immune system doesn't function properly. The trial includes different groups to test various patient preparation methods for the transplant. Candidates may qualify if they have experienced frequent or severe infections due to their immune condition. Donors must be healthy and willing to provide bone marrow or blood stem cells. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 chemotherapy is involved, it's possible that some medications might need to be adjusted. Please discuss this with the trial team for specific guidance.

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

Research has shown that transplants using blood or bone marrow from a donor (known as Allo BMT) have been studied in individuals with immune system issues. A large review of 58 studies, involving over 7,900 patients, indicated that these transplants are generally safe. The survival rate shortly after the transplant was 94%. However, risks such as infections or disease progression are common with these treatments.

For donors, research suggests that donating stem cells is usually safe. Short-term results for donors have been positive, even if they have received vaccines like the COVID-19 vaccine.

Overall, research suggests that Allo BMT is generally well-tolerated, but like any medical procedure, there are risks. It is important to discuss these risks with the medical team before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the different conditioning strategies being tested for bone marrow transplants in immune deficiency patients. Unlike traditional high-dose chemotherapy and radiation, the Reduced Intensity Conditioning (RIC) approaches use gentler treatments, which could mean fewer side effects and a better quality of life for patients. The Myeloablative Conditioning (MAC) arm uses more intense treatment, potentially leading to higher success rates in severe cases. The unique aspect of these trials is the exploration of shorter and reduced dosing, especially with the RIC-SHORT and RIC-MMF arms, which aim to balance treatment effectiveness with reduced toxicity. Overall, these trials aim to refine bone marrow transplant protocols, making them safer and more effective for patients with immune deficiencies.

What evidence suggests that this trial's treatments could be effective for primary immunodeficiency?

Research has shown that blood or marrow transplants from a donor can effectively treat primary immune system problems. In one study, 87% of patients showed no signs of infections after the transplant. This trial includes various treatment arms, such as the Myeloablative Conditioning Arm and the Reduced Intensity Conditioning Arms, which explore different conditioning regimens before the transplant. The treatment replaces faulty immune cells with healthy ones from a donor, addressing immune system issues. It is considered safe and effective, especially for young adults. Additionally, this type of transplant has cured severe immune system problems and is now being used for more adults. The success rates and outcomes make it a promising option for those with immune deficiencies. ^{1 2 3 5 6}

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 4-75 with primary immunodeficiencies that could be treated by a blood or marrow transplant. Donors must be healthy and at least 4 years old. Participants need to have certain immune system issues, like severe infections or autoimmune diseases, and good organ function. Pregnant women can't join, and participants must agree to use contraception for one year post-transplant.

Inclusion Criteria

I am between the ages of 4 and 75.

Ability to understand and sign a written informed consent document

Not pregnant or breastfeeding

Exclusion Criteria

Lack of adequate central venous access potential

I have had a condition where my lymphocytes grow abnormally.

I haven't had any cancer except for skin cancer in the last 5 years.

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

Recipients undergo chemotherapy 1-2 weeks before transplant day

1-2 weeks

Inpatient stay

Transplantation

Donor stem cell donation and transplantation procedure

1 day

Inpatient procedure

Post-transplant Hospitalization

Several-week hospital stay for monitoring and treatment post-transplant

Several weeks

Inpatient stay

Initial Follow-up

Participants remain near the clinic for about 3 months with weekly visits

3 months

Weekly visits (in-person)

Long-term Follow-up

Multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years

5 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Allo BMT

Trial Overview The trial tests if blood or bone marrow transplants from donors are safe and effective in treating various primary immunodeficiencies. It involves screening, pre-transplant assessments, chemotherapy before the transplant day, hospital stay for several weeks with follow-up visits up to five years.

How Is the Trial Designed?

Group I: 6/ RIC-SHORT Arm Experimental Treatment 3 Interventions

Reduced Intensity Conditioning with shortened duration and dose-reduced PTCy

Group II: 4/ RIC-MMF Arm Experimental Treatment 3 Interventions

Reduced Intensity Conditioning with MMF duration de-escalation design

Group III: 3/ MAC Arm-Closed with amendment L (07/05/2019) Experimental Treatment 3 Interventions

Myeloablative Conditioning Arm

Group IV: 2/ RIC Arm - Closed with Amendment L (07/05/2019) Experimental Treatment 3 Interventions

Reduced Intensity Conditioning Arm

Group V: 1/ IOC Arm-Closed with amendment L (07/05/2019) Experimental Treatment 3 Interventions

Immunosuppression Only Conditioning Arm

Group VI: 5/ Donor Arm Active Control 1 Intervention

Donor

Allo BMT is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Allogeneic Blood or Marrow Transplantation for:

• Primary Immunodeficiencies
• Severe Combined Immunodeficiency
• Wiskott-Aldrich Syndrome
• X-linked Lymphoproliferative Syndrome

Approved in United States as Allogeneic Blood or Marrow Transplantation for:

• Primary Immunodeficiencies
• Severe Combined Immunodeficiency
• Wiskott-Aldrich Syndrome
• X-linked Lymphoproliferative Syndrome
• Chronic Granulomatous Disease

Approved in Canada as Allogeneic Blood or Marrow Transplantation for:

• Primary Immunodeficiencies
• Severe Combined Immunodeficiency
• Wiskott-Aldrich Syndrome
• X-linked Lymphoproliferative Syndrome

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 94 infants with severe combined immune deficiency (SCID) who underwent bone marrow transplantation (BMT), those receiving stem cells from HLA-identical relatives (RID) had the highest survival rate at 92.3%, compared to 80.5% for HLA-matched unrelated donors (MUD) and 52.5% for HLA-mismatched related donors (MMRD).

MUD BMT resulted in better long-term immune reconstitution, achieving a full T-cell repertoire in 94.7% of patients, compared to only 61.1% in those receiving MMRD BMT, suggesting that MUD BMT is a more effective alternative when RID is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation for severe combined immune deficiency. Grunebaum, E., Mazzolari, E., Porta, F., et al.[2022]

In a study comparing allogeneic bone marrow transplantation (BMT) and immunosuppressive therapy (IST) for young patients with severe aplastic anemia, both treatments resulted in similar quality-adjusted life years (QALYs), with BMT at 6.77 and IST at 6.74.

The findings suggest that IST could be a viable alternative to BMT, especially when considering individual patient responses, as the effectiveness of IST can significantly influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia. Kanda, Y., Usuki, K., Inagaki, M., et al.[2023]

A survey of 441 adult survivors of allogenic blood and marrow transplant (allo-BMT) revealed that over 25% attended hospital clinics at least monthly and many required regular medical procedures, indicating a significant ongoing treatment burden.

Compliance with recommended long-term follow-up care decreased over time, highlighting the need for healthcare providers to recognize and address the challenges faced by survivors in managing their health post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment burden following allogeneic blood and marrow transplantation in NSW, Australia: a cross-sectional survey. McErlean, G., Brice, L., Gilroy, N., et al.[2022]

Allogeneic bone marrow transplants are an effective treatment for various hematologic diseases, including leukemia and aplastic anemia, with over 33,000 procedures performed between 1955 and 1990, particularly increasing in the late 1980s.

Recent advancements have allowed for successful transplants using unrelated or partially matched donors, although complications like graft failure and graft versus host disease remain significant challenges that can be predicted through risk factor assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of allogeneic bone marrow transplantation. Sobocinski, KA., Horowitz, MM., Rimm, AA., et al.[2019]

In a study of 214 T-cell-depleted bone marrow transplantations for severe combined immunodeficiencies (SCID), patients with B+ SCID had a significantly better disease-free survival rate (60%) compared to those with B- SCID (35%), highlighting the impact of SCID variant on treatment outcomes.

Factors such as the presence of lung infections before transplantation and the use of monoclonal antibodies for T-cell depletion were associated with poorer prognoses, indicating the need for careful patient assessment and tailored treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the european society for immunodeficiency. Bertrand, Y., Landais, P., Friedrich, W., et al.[2019]

Patients with severe combined immunodeficiency (SCID) who received HLA-identical bone marrow transplants (BMT) had a high survival rate of 76%, with a remarkable 97% cure rate observed in those treated since 1983, indicating the efficacy of this treatment.

The study found that conditioning regimens before BMT significantly improved the chances of sustained engraftment and normal B-cell function, highlighting the importance of pre-transplant preparation in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience of bone-marrow transplantation for severe combined immunodeficiency. Fischer, A., Landais, P., Friedrich, W., et al.[2019]

Allogeneic bone marrow transplantation (BMT) is a highly effective treatment option for various blood disorders, offering a 20% to 90% chance of long-term, disease-free survival after high-dose chemoradiotherapy.

While most patients do not have an HLA-compatible sibling donor, the use of unrelated HLA-compatible donors has been increasing and shows promising outcomes for treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation. Tabbara, IA.[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 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]

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]

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]

Allogeneic bone marrow transplantation (BMT) is a critical treatment for various hematologic diseases, particularly severe aplastic anemia and certain leukemias, with the best outcomes seen in younger patients and those in remission.

While BMT can offer a chance for cure, it carries significant risks, including graft failure, graft-versus-host disease, and long-term complications, which may limit its use to specialized centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation in the treatment of hematologic diseases. Yee, GC., McGuire, TR.[2021]

Citations

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

Successful outcome following allogeneic hematopoietic ... At last follow-up, 87% of the surviving patients had no evidence of persistent or recurrent infections. Allo-HSCT is safe and effective in young adult patients ...

2. 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 ...

3. 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 ...

4. astctjournal.org astctjournal.org/article/S2666-6367(24)00842-X/fulltext

Outcomes of Allogeneic Hematopoietic Stem Cell ... Allo-HCT provides promising outcomes for patients aged 70 or older with transplant-eligible diseases. Disease progression, followed by infections, is the ...

5. jacionline.org jacionline.org/article/S0091-6749(25)00516-0/fulltext

The impact of allogeneic hematopoietic stem cell ... Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure most severe IEIs. The indications for allo-HSCT have recently been extended to adults.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9534375/

The safety and short‐term outcomes of allogeneic ... This study preliminarily demonstrated that donors who received the SARS‐CoV‐2 vaccine did not affect the short‐term outcome of allo‐HSCT except ...