Stem Cell Transplant for SCID

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: ECOG status 3+, Heart failure, Liver issues, Psychiatric disorder, Seizure disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to prepare individuals with severe combined immune deficiency (SCID) for stem cell transplants. Researchers aim to determine if using low doses of medication without radiation is as effective as combining low-dose medication with radiation. Individuals with SCID who frequently experience infections or require nutritional support and have a stem cell donor match may be suitable candidates. Participants will receive chemotherapy, including drugs like Busulfan, and some will also undergo radiation before the transplant. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since participants will undergo a medication review and take chemotherapy drugs, it's possible that some medications may need to be adjusted. Please discuss your current medications with the study team for specific guidance.

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

Research has shown that treatments for SCID, such as Total Body Irradiation (TBI) combined with chemotherapy, have generally been safe in past studies. Over time, survival rates have significantly improved, with more than 70% of patients living at least five years after treatment. However, TBI can increase the risk of developing other cancers later, especially with high doses.

The chemotherapy drugs used in these trials, such as Busulfan and Sirolimus, have been employed in many treatments for different conditions. They are usually well-tolerated but can cause side effects like low blood counts and a higher risk of infections. Horse anti-thymocyte is another drug used to help the body accept new stem cells, and it can cause reactions like fever or rash, though these are often manageable.

Overall, studies have assessed the safety of these treatments, and they are generally considered safe. However, like any medical treatment, there are risks. Participants should be aware of these and discuss them with their healthcare team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial for Severe Combined Immunodeficiency (SCID) because they offer a fresh approach to tackling this challenging condition. Unlike traditional treatments that typically involve enzyme replacement or gene therapy, this trial explores the use of stem cell transplantation combined with innovative conditioning regimens. Group 1 receives Total Body Irradiation (TBI), which may enhance stem cell engraftment by creating space for new cells. Group 2 skips TBI, potentially reducing radiation-related side effects. This exploration could lead to more effective and safer treatment options for SCID patients, sparking hope for better outcomes.

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

Research has shown that using total body irradiation (TBI) in stem cell transplants for severe combined immune deficiency (SCID) yields promising results. In this trial, participants in Group 1 will receive TBI as part of their treatment. Studies have found that patients treated with TBI tend to live longer, with a 37% better survival rate compared to those not receiving TBI. Another study found that patients who received a gentler treatment approach, including TBI, had an 84% chance of stopping immunoglobulin therapy, which helps fight infections. These findings suggest that TBI, when combined with other treatments, may improve outcomes for SCID patients undergoing stem cell transplants. ^{1 2 6 7 8}

Who Is on the Research Team?

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 3-40 with SCID who have a stem cell donor. They must be HIV negative, not pregnant or breastfeeding, and able to stay near NIH for 3 months post-transplant. Participants should agree to use contraception and have no major organ failure or severe psychiatric conditions.

Inclusion Criteria

I have physical signs of auto-immunity, like severe rashes or joint pain without infection.

I have a chronic lung condition confirmed by tests.

I have skin issues like molluscum or warts, yeast infections on skin or mucous membranes, and low levels of antibodies.

Exclusion Criteria

I have seizures that are not controlled by medication.

Pregnant or lactating females.

I do not have any major illnesses or organ failures that would make a stem cell transplant from a donor risky.

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 a busulfan-based conditioning regimen with or without total body irradiation (TBI) and immune suppression with h-ATG and sirolimus to prepare for stem cell transplant

10 days

Inpatient stay

Stem Cell Transplantation

Participants undergo stem cell transplantation using cells from a matched related or unrelated donor

1 day

Inpatient stay

Immediate Post-Transplant Recovery

Participants remain in the hospital for 30 days post-transplant for monitoring and initial recovery

30 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with weekly visits for 3 months, then annual visits for 5-6 years

6 years

Weekly visits for 3 months, then annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Busulfan
• Horse -Anti-thymocyte
• Sirolimus
• Total Body Irradiation (TBI)

Trial Overview The study tests if low-dose drugs alone or combined with radiation are effective in preparing SCID patients for stem cell transplants. It involves hospital admission, various health assessments, chemotherapy (with some receiving radiation), followed by the transplant procedure.

How Is the Trial Designed?

Group I: Group 1 Active Control 5 Interventions

Patients will be treated with Total Body Irradiation (TBI)

Group II: Group 2 Active Control 4 Interventions

Patients will not be treated with Total Body Irradiation (TBI)

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

Approved in United States as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Malignant lymphoma
• Bone marrow transplantation conditioning

Approved in European Union as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 43 children with acute lymphoblastic leukemia (ALL) undergoing allogeneic stem cell transplant, those receiving total body irradiation (TBI) had a significantly better event-free survival (EFS) rate of 58% compared to 29% for those receiving busulfan (Bu) after a median follow-up of 43 months.

The results indicate that busulfan is less effective than TBI, particularly for patients receiving stem cells from unrelated donors, where EFS was only 20% for Bu compared to 57% for TBI, suggesting that TBI may be the preferred conditioning regimen for pediatric ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bunin, N., Aplenc, R., Kamani, N., et al.[2013]

The studies compared the efficacy of busulfan versus total body irradiation (TBI) as preparative treatments for hematopoietic transplantation in patients with acute myeloid leukemia (AML).

The findings from these comparisons could provide insights into the optimal conditioning regimens for improving treatment outcomes in AML patients undergoing transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Busulfan or TBI: answer to an age-old question. Champlin, RE.[2021]

In a meta-analysis of 15 randomized controlled trials involving 10,160 pediatric patients, total body irradiation plus cyclophosphamide (TBI/CY) was found to be more effective than busulfan plus cyclophosphamide (BU/CY) in reducing transplant failure rates and improving long-term disease-free survival rates.

The TBI/CY regimen also demonstrated a lower incidence of adverse reactions compared to the BU/CY regimen, indicating it may be a safer option for pediatric hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. Wang, X., Mu, D., Geng, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6019104/

Long term outcomes of severe combined immunodeficiency Over time, the 5-year overall survival has improved from 56% in patients treated prior to 1995, to currently greater than 70% and depending on donor and age at ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4641002/

Radiation-Sensitive Severe Combined Immunodeficiency For those who were treated with RIC or MAC there was an 84% (CI 69–93%) chance of ceasing gammaglobulin supplementation vs a 41% (CI 31–52%) ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1401177

Transplantation Outcomes for Severe Combined ... Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024024467

Review Article Efficacy and Safety of Total Body Irradiation ... This meta-analysis includes 20 cohort studies and one RCT. The relative risk (RR) for OS was 1.37 (95% CI: 1.20-1.57), while the RR for EFS was 1.28 (95% CI: ...

5. jacionline.org jacionline.org/article/S0091-6749(15)00589-8/abstract

Radiation-sensitive severe combined immunodeficiency A reduced-intensity regimen using fludarabine and low-dose cyclophosphamide might be effective for patients with LIG4, NHEJ1, and NBS1 defects, although more ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11646108/

Long‐Term Outcomes of Reduced‐Toxicity Conditioning ... 8‐Gy TBI/FLU/CY RTC was safe in children with hematological malignancies, regardless of the donor source.

7. tandfonline.com tandfonline.com/doi/full/10.1080/07853890.2022.2125171

Full article: Outcomes of allogeneic haematopoietic stem ... We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy.

8. ashpublications.org ashpublications.org/blood/article-abstract/133/26/2790/272767/Total-body-irradiation-dose-and-risk-of-subsequent

Total body irradiation dose and risk of subsequent neoplasms ... SMN risk was highest in survivors exposed to high-dose unfractionated (600-1200 cGy) or very high-dose fractionated (1440-1750 cGy) TBI.