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

Trial Summary

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.

What data supports the effectiveness of the treatment Allo BMT for immune deficiency?

Allogeneic bone marrow transplantation (Allo BMT) is considered an effective treatment for various immune deficiency disorders, as it is the only cure for many primary immune deficiency disorders and inherited bone marrow failure syndromes. Studies have shown that it is also effective for severe combined immunodeficiency (SCID), with a high survival rate in patients receiving HLA-identical transplants. ^{1 2 3 4 5}

Is allogeneic bone marrow transplantation generally safe for humans?

Allogeneic bone marrow transplantation (BMT) can be risky, with potential complications like graft failure, graft-versus-host disease (GVHD), and infections. Long-term effects may include lung problems, cataracts, and other health issues. While it can be life-saving for certain conditions, it is associated with significant risks and is usually done in specialized centers. ^{1 6 7 8 9}

How is the treatment Allo BMT different from other treatments for immune deficiency?

Allo BMT is unique because it involves transplanting healthy bone marrow from a donor to replace the patient's faulty immune system, offering a potential cure for many immune deficiencies. Unlike other treatments that may only manage symptoms, this approach aims to restore normal immune function by using donor stem cells. ^{2 10 11 12 13}

What is the purpose of this trial?

Background: Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies. Eligibility: Donors: Healthy people ages 4 or older Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant Design: Participants will be screened with medical history, physical exam, and blood tests. Participants will have urine tests, EKG, and chest x-ray. Donors will have: Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone. OR Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm. Possible vein assessment or pre-anesthesia evaluation Recipients will have: Lung test, heart tests, radiology scans, CT scans, and dental exam Possible tissue biopsies or lumbar puncture Bone marrow and a small piece of bone removed by needle in the hipbone. Chemotherapy 1-2 weeks before transplant day Donor stem cell donation through a catheter put into a vein in the chest or neck Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures. After discharge, recipients will: Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission. Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years.

Research Team

Dimana Dimitrova, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

I have a donor who is a close match to my tissue type.

Ability to understand and sign a written informed consent document

Exclusion Criteria

I have had a condition where my lymphocytes grow abnormally.

Lack of adequate central venous access potential

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

References

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

Allogeneic bone marrow transplantation in the treatment of hematologic diseases. [2021]

2. 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]

3. France pubmed.ncbi.nlm.nih.gov

Current status of allogeneic bone marrow transplantation. [2019]

4. United States 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. [2019]

5. England pubmed.ncbi.nlm.nih.gov

European experience of bone-marrow transplantation for severe combined immunodeficiency. [2019]

6. 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]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

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

Long-term treatment burden following allogeneic blood and marrow transplantation in NSW, Australia: a cross-sectional survey. [2022]

10. 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]

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

Allogeneic bone marrow transplantation. [2019]

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

Bone marrow transplantation for severe combined immune deficiency. [2022]

13. Japan pubmed.ncbi.nlm.nih.gov

Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia. [2023]