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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Severe combined immune deficiency (SCID) is a group of conditions where the immune system does not work properly. The only cure for most SCIDs is a stem cell transplant (getting cells from a donor). These transplants can have serious complications. Before the transplant, people often get high doses of drugs and radiation to prepare the body to accept the cells from the donor. Researchers want to see if low doses of drugs alone without radiation work just as well as low doses of drugs with radiation for SCID patients getting stem cell transplants. Objective: To test a set of drugs with or without radiation given before a stem cell transplant. Eligibility: People ages 3-40 who have SCID and who have a stem cell donor - either related or unrelated. Design: Participants will be admitted to the hospital 10 days before transplant. They will undergo: medical history medication review physical exam blood and urine tests (may include a 24-hour urine collection) heart, lung, and breathing tests imaging scans bone marrow sample nutrition assessment dental exam eye exam meeting with a social worker. Participants will get a plastic port called a central line. It is a hollow tube that is placed in the upper chest. It will be used to give medicines and take blood. All participants will take chemotherapy drugs. Some will get radiation. Participants will have a stem cell transplant. They will get the cells as an infusion through their central line. They will stay in the hospital for 30 days after transplant. Participants must stay within 1 hour of NIH for 3 months after transplant. During this time, they will have follow-up visits at NIH at least once a week. Then they will have follow-up visits once or twice a year for 5-6 years.

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.

What data supports the effectiveness of the treatment for SCID involving Busulfan, Busulfex, Myleran, Horse -Anti-thymocyte, Sirolimus, Rapamune, and Total Body Irradiation (TBI)?

Research shows that Busulfan and Total Body Irradiation (TBI) are used in stem cell transplants for leukemia, with Busulfan being an alternative to TBI due to fewer long-term side effects. This suggests potential effectiveness in similar transplant settings, like SCID, though specific data for SCID is not provided. ^{1 2 3 4 5}

Is stem cell transplant for SCID safe?

Stem cell transplants using busulfan or total body irradiation (TBI) have been studied for safety in leukemia patients. Busulfan has been associated with higher risks of liver disease, bladder issues, seizures, and graft-versus-host disease (a condition where the donor cells attack the recipient's body) compared to TBI. TBI can cause long-term issues like impaired growth and intellectual development in children. ^{1 2 4 6 7}

How is the stem cell transplant treatment for SCID different from other treatments?

This treatment for SCID is unique because it combines busulfan, horse anti-thymocyte, sirolimus, and total body irradiation (TBI), which is a novel combination not typically used together for this condition. While TBI is often used in other conditions, it can cause significant side effects, and busulfan is sometimes used as an alternative. The combination aims to balance effectiveness and reduce potential toxicities. ^{1 2 3 4 5}

Research Team

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

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

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

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

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. [2017]

3. England 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. [2013]

4. England 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. [2023]

5. Austria pubmed.ncbi.nlm.nih.gov

[High-dose busulfan with subsequent bone marrow transplantation in poor-risk forms of leukemia]. [2013]

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

A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation in acute lymphoblastic leukemia: better long term event-free survival with conditioning regimens containing total body irradiation. [2013]