Stem Cell Transplant for Primary Immunodeficiency

Overseen By Christen Ebens, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, HIV, Hepatitis, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a stem cell transplant treatment for individuals with primary immunodeficiency disorders. It aims to determine the effectiveness of these transplants for people with specific immune system issues, such as severe combined immunodeficiency (SCID) or Wiskott-Aldrich syndrome. Treatment paths vary depending on the condition, with each involving a distinct preparation and transplant process. Suitable candidates have been diagnosed with certain immune disorders that impact daily life, such as frequent infections or severe symptoms. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance treatment options for immune disorders.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that stem cell transplants from donors are generally safe and effective for individuals with severe immune system problems. Young adults, in particular, have experienced positive outcomes with this treatment. It is a standard approach, widely used and trusted by doctors for these conditions.

However, some studies suggest that results can vary, especially for older patients or those with specific immune issues. Although survival rates have improved over time, individual outcomes can differ based on factors such as age and the type of immune problem.

In summary, while this treatment is usually safe and well-tolerated, personal factors can affect results. Always consult healthcare providers for information tailored to individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the stem cell transplant protocol for primary immunodeficiency because it offers a tailored approach for different conditions. Unlike typical treatments that may involve lifelong medication or regular infusions, this protocol uses allogeneic hematopoietic stem cell transplants to potentially provide a long-term solution. Each arm of the protocol is designed with specific conditioning regimens that balance effectiveness and toxicity. For example, the fully myeloablative regimen aims for maximal immune system reset, while the reduced intensity and toxicity regimens offer less harsh alternatives for those who can't tolerate stronger treatments. This precision in treatment approach could lead to better outcomes and improved quality of life for patients with various immune deficiencies.

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

Research has shown that using donor stem cells to replace a patient's faulty immune system is a common treatment for primary immune deficiencies. This method, known as allogeneic hematopoietic stem cell transplantation (HSCT), uses healthy stem cells from a donor. In this trial, participants will receive different treatment regimens, such as a fully myeloablative regimen, reduced toxicity ablative regimen, reduced intensity conditioning, or no preparative regimen, based on their specific condition. Studies have found that children with severe immune deficiencies often experience significant improvements or even cures with this treatment. Used for over 40 years, it remains a key treatment option. While results can vary, especially in adults, overall success rates have improved over time. ^{1 2 3 4 6}

Who Is on the Research Team?

Christen Ebens, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people aged 0-50 with primary immune deficiencies or histiocytic disorders, such as SCID, Omenn's Syndrome, Wiskott-Aldrich syndrome. Participants need a suitable stem cell donor and good organ function. Those with acute hepatitis, severe liver issues, active infections including HIV, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

I am 50 years old or younger.

I have been diagnosed with an immune system disorder like SCID or CGD.

I have a suitable stem cell donor or cord blood unit that matches me.

Exclusion Criteria

Pregnant or breastfeeding

I have severe liver damage or hepatitis.

I do not have an active, uncontrolled infection or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants receive a preparative regimen based on their condition, which may include myeloablative, reduced toxicity, or reduced intensity conditioning, followed by stem cell infusion on day 0.

2 weeks

Engraftment Monitoring

Participants are monitored for neutrophil engraftment, defined as the first day of three consecutive days where the neutrophil count is 500 cells/mm3 or greater.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness, including incidence of acute and chronic Graft-Versus-Host Disease, overall survival, and transplant-related mortality.

6 months

Long-term Follow-up

Participants are monitored for long-term outcomes such as disease-free survival and incidence of chronic Graft-Versus-Host Disease.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoetic Stem Cell Transplant

Trial Overview The trial tests a standard care approach using allogeneic hematopoietic stem cell transplant (HSCT) combined with drugs like Alemtuzumab at different doses, Melphalan, Busulfan, Cyclophosphamide and Fludarabine phosphate to treat various primary immune deficiencies.

How Is the Trial Designed?

Group I: Arm D: No Preparative Regimen Experimental Treatment 1 Intervention

For use in patients with complete SCID phenotype with no evidence of maternal engraftment or residual immune function who will be receiving their stem cell transplantation from a genotypically matched donor.

Group II: Arm C: Reduced Intensity Conditioning Experimental Treatment 4 Interventions

For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m\^2 IV on days -8 through -4, melphalan 140 mg/m\^2 IV on day -3 and stem cell infusion on day 0.

Group III: Arm B: Reduced Toxicity Ablative Regimen Experimental Treatment 4 Interventions

For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m\^2 IV on days -5 through -2 and stem cell infusion on day 0.

Group IV: Arm A: Fully Myeloablative regimen Experimental Treatment 5 Interventions

For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.

Allogeneic Hematopoetic Stem Cell Transplant is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Approved in China as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Approved in Switzerland as Allogeneic Hematopoietic Stem Cell Transplant for:

• Primary Immune Deficiencies
• Leukemia
• Myelodysplastic Syndromes
• Myeloproliferative Neoplasms
• Aplastic Anemia
• Severe Combined Immunodeficiency (SCID)
• Thalassemia
• Sickle Cell Disease

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

Allogeneic hematopoietic stem cell transplantation can potentially cure primary immunodeficiencies by establishing a functioning immune system, significantly improving patient prognosis.

Recent analyses of large patient cohorts indicate that clinical outcomes of stem cell transplantation for severe combined immunodeficiency diseases have steadily improved, highlighting advancements in treatment modalities, including options without cytoreductive conditioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation for treatment of immunodeficiency. Friedrich, W., Müller, SM.[2018]

Hematopoietic stem cell transplantation is the best treatment for patients with primary immunodeficiencies, especially when using stem cells from HLA-identical donors, although this is only feasible for a limited number of patients.

HLA-mismatched or haploidentical stem cell transplants are increasingly being used for various severe primary immunodeficiencies, and factors like donor selection, infection management, and patient conditioning before the transplant significantly influence the success of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cell transplantation in children with primary immunodeficiencies]. Kelecić, J., Rajić, L., Tjesić-Drinković, D.[2009]

Umbilical cord blood is a promising alternative stem-cell source for children with severe primary T-cell immunodeficiencies, showing rapid and reliable recovery of immune function after transplantation in a study of 6 children.

The transplantation resulted in low rates of graft-versus-host disease (GvHD) and effective immune reconstitution, with stable development of T-cells, B-cells, and natural killer cells, indicating its safety and efficacy compared to other donor sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. Knutsen, AP., Wall, DA.[2019]

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment for primary immunodeficiencies, particularly effective when applied early in the disease course to prevent severe complications from infections.

Recent analyses of large patient cohorts indicate that HSCT has led to significant improvements in outcomes and prognosis for patients with disorders like severe combined immunodeficiency (SCID).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for treatment of primary immunodeficiency disorders. Müller, SM., Friedrich, W.[2007]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown an overall survival rate of 83.4% at 5 years for children with inborn errors of immunity (IEI), based on a study of 67 children over 32 years.

Recent advancements, particularly the use of TCR αβ/CD19-depleted haploidentical transplants, have significantly reduced the incidence of severe acute graft-versus-host disease (aGvHD) from 61.5% to 20%, demonstrating improved safety and efficacy in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience. Dell'Orso, G., Bagnasco, F., Giardino, S., et al.[2023]

In a study of 919 patients who underwent allogeneic stem cell transplantation for primary immunodeficiencies, 3-year survival rates were significantly higher for HLA-identical transplants in SCID patients (77%) compared to mismatched transplants (54%), indicating the importance of donor matching for better outcomes.

The study also found that stem cell transplantation can effectively cure non-SCID immunodeficiencies, with survival rates of 71% for genotypically HLA-matched donors and 59% for unrelated donors, suggesting that unrelated donor grafts can be nearly as effective as those from genetically identical relatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Antoine, C., Müller, S., Cant, A., et al.[2019]

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 &#945;&#946;+ 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 hematopoietic stem cell transplantation can effectively cure primary immunodeficiencies, especially when using bone marrow from an HLA-identical sibling donor.

In a unique case, a younger sibling underwent three bone marrow harvests at ages 1.3 to 4 years, successfully providing transplants for three siblings with the same immunodeficiency, highlighting the potential for multiple donations despite ethical and safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethical considerations of using a single minor donor for three bone marrow harvests for three HLA-matched siblings with primary immunodeficiency. Parikh, SH., Pentz, RD., Haight, A., et al.[2019]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a safe and effective treatment for adult patients with primary immunodeficiencies (PID), showing an overall survival rate of 80.4% at 9 months post-transplant, with 100% survival for patients with chronic granulomatous disease (CGD).

The study involved 32 adult patients, all of whom successfully engrafted and demonstrated over 90% donor chimerism and immune reconstitution, indicating that allo-HSCT can lead to significant clinical improvement without active PID-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curative allogeneic hematopoietic stem cell transplantation following reduced toxicity conditioning in adults with primary immunodeficiency. Marçais, A., Mahlaoui, N., Neven, B., et al.[2022]

In a study of 20 patients with primary immunodeficiency diseases, hematopoietic stem cell transplants resulted in a 65% overall survival rate, indicating a promising outcome for this treatment.

The median engraftment times for neutrophils and platelets were 14.25 days and 24.7 days, respectively, with graft-versus-host disease occurring in 30% of patients, highlighting both the efficacy and potential complications of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic Stem Cell Transplant for Primary Immunodeficiency Diseases: A Single-Center Experience. Patiroglu, T., Akar, HH., Unal, E., et al.[2018]

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a safe and effective treatment for young adults with severe primary immunodeficiencies (PIDs), showing an overall survival rate of 85.2% at 3 years across 29 patients.

Patients with PIDs other than chronic granulomatous disease (CGD) had even better outcomes, with a 3-year survival rate of 88.9%, and 87% of surviving patients showed no signs of persistent infections, indicating strong immune reconstitution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency. Fox, TA., Chakraverty, R., Burns, S., et al.[2022]

In a study of seven pediatric patients with various primary immunodeficiencies who underwent eight hematopoietic stem cell transplants, the status of patients before the transplant was identified as the most critical factor influencing outcomes, highlighting the importance of early diagnosis and timely referral for treatment.

Out of the seven patients, four survived and are doing well after the transplant, while complications such as graft failure and regimen-related toxicity were significant challenges, indicating that while the procedure can be effective, careful management of pre-existing conditions is essential for improving survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies: Hospital Israelita Albert Einstein experience. Fernandes, JF., Kerbauy, FR., Ribeiro, AA., et al.[2016]

Hematopoietic stem cell transplantation (SCT) has shown an 80% cure rate for children with primary immunodeficiencies when using HLA-matched sibling donors, highlighting its efficacy as a treatment option.

Early diagnosis and timely SCT are crucial for improving outcomes, as delays can lead to irreversible complications from the disease or infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for primary immunodeficiencies: King Faisal Specialist Hospital experience from 1993 to 2006. Al-Ghonaium, A.[2008]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6225386/

Successful outcome following allogeneic hematopoietic ... Children with severe PIDs have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which has been the major therapeutic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01652092

Allogeneic Hematopoietic Stem Cell Transplant for Patients ... This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies. Detailed ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3357108/

Allogeneic Hematopoietic Cell Transplantation for Primary ... Allogeneic hematopoietic cell transplantation (HCT) has been employed for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, ...

4. ashpublications.org ashpublications.org/hematology/article/2020/1/649/474361/Allogeneic-hematopoietic-stem-cell-transplantation

Allogeneic hematopoietic stem cell transplantation in adults ... Published retrospective data for HSCT in adult patients with complex CVID have indicated worse outcomes than for other PID patients after ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497122001422

Hematopoietic stem cell transplantation for Wiskott-Aldrich ... Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/condition/1023/allogeneic-hematopoietic-stem-cell-transplant?activelyRecruiting=false&page=15

Allogeneic Hematopoietic Stem Cell Transplant This protocol is a retrospective review of donor search results for patients with inherited immunodeficiency diseases requiring allogeneic hematopoietic stem ...