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

Trial Summary

What is the purpose of this trial?

Background: During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications. Objective: To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them. Eligibility: People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors Design: Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow. Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests CT or PET scans Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow. Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications. Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years

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.

What data supports the effectiveness of the drug Alemtuzumab in treating immune deficiency syndrome?

Research shows that Alemtuzumab, when used in stem cell transplants, can effectively reduce the risk of graft-versus-host disease (GVHD), a common complication, without significantly increasing life-threatening infections or relapse rates compared to conventional treatments. ^{1 2 3 4 5}

Is stem cell transplant with Alemtuzumab generally safe for humans?

Alemtuzumab, used in stem cell transplants, can reduce complications like graft-versus-host disease but may delay immune recovery, increasing infection risk. Some cases report serious side effects like kidney failure, but these are rare. Overall, it shows promise in reducing transplant-related complications, though more studies are needed to confirm long-term safety. ^{1 2 3 4 5}

What makes this treatment for immune deficiency syndrome unique?

This treatment is unique because it uses alemtuzumab (Campath), a monoclonal antibody that targets specific immune cells to prevent graft-versus-host disease (GVHD) in stem cell transplants, reducing the risk of severe complications compared to traditional methods. It combines multiple drugs to prepare the body for transplant, aiming to improve outcomes by minimizing immune reactions and enhancing engraftment. ^{1 2 3 4 6}

Research Team

Sung-Yun Pai, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. [2023]

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

Pretransplant conditioning with Campath-1H (alemtuzumab) in pediatric matched unrelated hematopoietic stem cell transplants: an institutional experience. [2017]

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

Alemtuzumab in stem cell transplantation. [2021]

4. United States 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. [2017]

5. Italy pubmed.ncbi.nlm.nih.gov

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

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

Conditioning with purine analogs leads to good engraftment rates of immunodepleted grafts for aplastic anemia. [2017]