Stem Cell Transplant for Immune Deficiency Syndrome

Overseen By Shannon L Knight, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: HIV, Brain metastases, Uncontrolled illness, 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

Compensation: Varies

Number of Visits: 1

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a stem cell transplant can effectively treat individuals with primary immunodeficiency disease, a condition where the immune system doesn't function properly. The procedure transfers blood stem cells from a healthy donor to the patient, with the hope that these cells will develop into a new, functioning immune system. This trial is suitable for individuals aged 4-69 who experience significant health issues due to their condition and have not found relief through standard treatments. Participants will undergo a series of screenings and must stay in the hospital for a period after the transplant to monitor recovery and manage any complications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from cutting-edge therapy.

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, it mentions that participants will receive medications through a catheter to prevent complications, so it's best to discuss your current medications with the trial team.

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

In a previous study, alemtuzumab, one of the treatments used in the trial, caused infusion-related reactions in 95% of patients, indicating that most experienced some reactions during administration. About 74% of the patients developed infections, and 30% experienced thyroid problems. Despite these side effects, the overall death rate among patients was lower than the U.S. average.

Research has shown that allogeneic hematopoietic stem cell transplantation (HSCT), another treatment in the trial, is safe for individuals with certain immune system issues. It has a high survival rate, with 94% of patients surviving the procedure. However, it carries risks such as graft-versus-host disease, where the donated cells attack the patient's body, though these risks can be managed with care.

Both treatments have demonstrated benefits in treating other conditions, providing some evidence of safety. However, like all medical procedures, they come with risks. It is important to weigh these risks against the potential benefits when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using stem cell transplants for treating immune deficiency syndromes because this approach targets the root cause by replacing defective immune cells with healthy ones. This technique, known as Allogeneic Hematopoietic Stem Cell Transplantation (HSCT), offers a potential cure rather than just managing symptoms. The treatment includes carefully chosen conditioning regimens with drugs like Alemtuzumab and Fludarabine, which aim to minimize toxicity while effectively preparing the body for the transplant. Unlike standard treatments that usually focus on alleviating symptoms or boosting the immune system temporarily, this method holds promise for long-lasting and possibly permanent immune system restoration.

What evidence suggests that this trial's treatments could be effective for immune deficiency syndrome?

Research has shown that stem cell transplants can effectively treat immune deficiency syndromes. In this trial, participants will receive allogeneic hematopoietic stem cell transplants, which studies indicate have high success rates, with about 93% of patients surviving for at least five years. These transplants are considered a cure for severe immune disorders. However, risks include graft-versus-host disease, where donor cells attack the recipient's body, occurring in about 22% of cases. Some participants in this trial may receive Alemtuzumab, a drug used in certain transplant treatments, which can help manage immune-related conditions but may cause side effects like reactions during infusion. Overall, while these treatments are promising, they come with significant risks and require careful consideration. ^{1 2 3 6 7}

Who Is on the Research Team?

Sung-Yun Pai, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for people aged 4-69 with primary immunodeficiency diseases who haven't responded to standard treatments or have no other options. Participants need functioning major organs, a matched donor, and must agree to use contraception. Excluded are those with brain metastases, HIV, severe allergies to study drugs, uncontrolled illnesses, certain psychiatric conditions, pregnant or breastfeeding women.

Inclusion Criteria

I will have an adult caregiver with me at all times for the first 100 days after my transplant.

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

I may have an immune defect based on my symptoms, even though no genetic cause has been found.

Exclusion Criteria

Pregnant women

Active psychiatric disorder deemed to compromise compliance with the transplant protocol

Patients receiving any other investigational agents except virus-specific therapy

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 conditioning regimen with fludarabine and busulfan, and possibly alemtuzumab, to prepare for the transplant

6 days

Inpatient stay

Transplantation

Participants receive hematopoietic stem cell transplant

1 day

Inpatient stay

Post-Transplant Hospitalization

Participants remain hospitalized for monitoring and receive medications to prevent complications

4 weeks

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits on days 30, 60, 100, 180, 360, and annually for 5 years

5 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Allogeneic HSCT
• Busulfan
• Cyclophosphamide
• Fludarabine
• Mycophenolate mofetil (MMF)
• Tacrolimus (Tacro)

Trial Overview

The trial tests if stem cell transplants can cure primary immunodeficiencies. It involves screening donors and recipients; pre-transplant exams; hospitalization for the transplant procedure including medications through a catheter; post-transplant monitoring with regular visits up to five years.

How Is the Trial Designed?

Group I: Arm A Active Control 8 Interventions

Low Intensity, Intermediate Intensity and High Intensity Conditioning with or without alemtuzumab

Group II: Arm B Active Control 9 Interventions

Intermediate Intensity Conditioning with or without Alemtuzumab

Alemtuzumab is already approved in United States, European Union for the following indications:

Approved in United States as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Approved in European Union as Lemtrada for:

• Multiple sclerosis

Approved in European Union as Campath for:

• Chronic lymphocytic leukemia

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 17 pediatric patients undergoing matched unrelated hematopoietic stem cell transplantation (HSCT) with Campath-1H, the incidence of grade I-II acute graft versus host disease (GVHD) was only 29.4%, and no cases of chronic GVHD were observed, suggesting effective reduction of GVHD risk.

Despite a 35.3% relapse rate of primary disease, the overall survival rates were high at 100% at 100 days and 94% at one year, indicating that Campath-1H does not significantly increase the risk of life-threatening infections or relapse compared to conventional regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretransplant conditioning with Campath-1H (alemtuzumab) in pediatric matched unrelated hematopoietic stem cell transplants: an institutional experience. Nageswara Rao, AA., Kumar, R., Altaf, S., et al.[2017]

In a study of 30 patients undergoing allogeneic stem cell transplantation (SCT) for severe marrow aplasia, all patients successfully engrafted within a median of 12 days, demonstrating the effectiveness of a purine analog-based conditioning regimen combined with alemtuzumab.

Despite two cases of delayed graft failure, the overall outcomes were excellent, with all patients surviving and being transfusion-free at a median follow-up of 1,560 days, indicating that this approach is safe and effective for preventing graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioning with purine analogs leads to good engraftment rates of immunodepleted grafts for aplastic anemia. Novitzky, N., Thomas, V., du Toit, C.[2017]

Alemtuzumab (Campath 1H), a monoclonal antibody targeting CD52 on B and T cells, is increasingly used as a conditioning agent for bone marrow transplantation, but it can have serious side effects.

In a case study of a 37-year-old woman, acute renal failure and disseminated intravascular coagulation (DIC) occurred after receiving Campath, leading to the abortion of her transplant and ongoing dialysis, highlighting the need for caution and further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute renal failure and disseminated intravascular coagulation following an idiosyncratic reaction to Alemtuzumab (Campath 1H) or fludarabine. Osborne, WL., Lennard, AL.[2017]

Alemtuzumab (CAMPATH-1H) is an effective monoclonal antibody for depleting T-cells in stem cell transplantation, significantly reducing the risk of graft-versus-host disease (GVHD) while maintaining low rates of graft rejection.

Current protocols for using alemtuzumab, either added to stem cell infusions or administered before transplantation, show excellent control of GVHD and have been associated with reduced transplant-related mortality, particularly from infections, although further clinical trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab in stem cell transplantation. Hale, G.[2021]

A population pharmacokinetic model for alemtuzumab was developed using data from 206 pediatric patients, revealing that body weight significantly affects the drug's clearance and distribution, which can lead to variable drug exposure.

The study suggests that the current standard dosing method may not be optimal for all children, and individualized dosing based on this model could improve treatment outcomes and reduce toxicity associated with alemtuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. Admiraal, R., Jol-van der Zijde, CM., Furtado Silva, JM., et al.[2023]

In a study of 127 patients undergoing allogeneic hematopoietic cell transplantation, reducing the dose of alemtuzumab to 10 mg for graft-versus-host disease (GVHD) prophylaxis was feasible and did not significantly increase the risk of severe aGVHD compared to higher doses.

The study found that while there were no significant differences in the incidence of severe aGVHD across different alemtuzumab doses, the 20 mg dose showed a significant difference in the incidence of aGVHD grade II-IV compared to the 40 mg dose, suggesting that lower doses may be effective in preventing GVHD while minimizing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation. Bertz, H., Spyridonidis, A., Wäsch, R., et al.[2017]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10920415/

Real-World Retrospective Analysis of Alemtuzumab Outcomes ...

Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed ...

2.

lemtrada.com

lemtrada.com/about/clinical-study-relapses

LEMTRADA® (alemtuzumab) Clinical Study Results

13% of patients who took LEMTRADA experienced confirmed disability progression compared with 21% of those who took Rebif.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2211034820306933

A real-world cohort analysis of alemtuzumab outcomes in ...

Over an average of 2.6 years follow-up, there were small but significant improvements in neurological disability scores, and a 61% rate of the composite “No ...

4.

neurology.org

neurology.org/doi/10.1212/WNL.0000000000004354

Alemtuzumab CARE-MS II 5-year follow-up

This study provides Class III evidence that efficacy outcomes were maintained or further improved with alemtuzumab during extended follow-up in patients with ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5522829/

Alemtuzumab: a review of efficacy and risks in the treatment of ...

The study confirmed the results of CAMMS2237 in terms of all clinical outcomes. Higher efficacy compared to IFN β 1a was confirmed regardless of ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2211034820307914

Alemtuzumab outcomes by age: Post hoc analysis from the ...

In Year 8, 61%–86% of alemtuzumab-treated patients in each age cohort were free of MRI disease activity. Treatment effect of alemtuzumab on slowing of ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8978465/

Benefit/risk following review of trial and post-marketing data

Over 9 years, 19 (1.6%) deaths (2.1 per 1000 patient-years) were reported in patients exposed to alemtuzumab 12 mg (overall age-adjusted US death rate: 7.3 per ...