Haploidentical HCT for Primary Immunodeficiency

Recruiting at 1 trial location

Overseen By Jade Hanson, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins All Children's Hospital

Disqualifiers: Pregnancy, HIV, Uncontrolled infections, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for stem cell transplants in individuals with certain immune system issues, such as primary immunodeficiency or related disorders. The aim is to determine the safety and effectiveness of Haploidentical Hematopoietic Cell Transplantation, which uses specially processed cells from a half-matched family donor. Suitable candidates for this trial include those with severe combined immunodeficiency or chronic granulomatous disease who have a family member that is a half-match for stem cell donation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

What prior data suggests that this transplantation method is safe?

Research has shown that haploidentical hematopoietic cell transplantation is generally safe. In past studies, about 84% of patients survived three years post-transplant, indicating positive outcomes for most. However, approximately 22% experienced acute GvHD, where new cells attack the body, ranging from mild to severe. Graft failure, where the transplant doesn't work as planned, was rare, occurring in about 4% of cases.

Other studies have reported similar findings, with nearly 80% survival rates for patients with primary immune deficiencies. Most deaths resulted from infections before the transplant, not the procedure itself. This suggests the procedure is generally well-tolerated and offers a good chance of success for those without a fully matched donor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Haploidentical Hematopoietic Cell Transplantation (HCT) is unique because it offers a new way to treat primary immunodeficiency by using TCR alpha beta T cell depletion. This approach is different from traditional methods, which typically rely on fully matched donor transplants. By allowing for partially matched donors, this treatment expands the pool of potential donors, making it easier to find a match for patients. Researchers are excited because this method could lead to fewer complications and better outcomes in patients who have limited donor options.

What evidence suggests that this haploidentical transplantation method is effective for primary immunodeficiency?

Research has shown that stem cell transplants from half-matched donors, known as haploidentical hematopoietic cell transplants, yield promising results for treating primary immune system disorders. In this trial, participants will receive a haploidentical hematopoietic cell transplant with TCR alpha beta T cell depletion. One study reported a five-year survival rate of about 72% in patients with various immune deficiencies, such as severe combined immunodeficiency (SCID) and Wiskott-Aldrich syndrome. Another study found that many patients regained important immune functions within 3 to 6 months after the transplant. Additionally, a study involving multiple centers reported an 80% survival rate in patients with a specific genetic deficiency. These findings suggest that this treatment could effectively improve health outcomes for people with primary immunodeficiencies. ^{1 4 6 7 8}

Who Is on the Research Team?

Deepak Chellapandian, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children with primary immunodeficiency or inherited metabolic disorders. Eligible participants include those with various immune system issues, autoimmune diseases, and certain metabolic conditions that could benefit from a stem cell transplant. Pregnant individuals, patients with HIV or uncontrolled infections, prior organ transplants, or severe graft-versus-host disease are excluded.

Inclusion Criteria

I have a disorder that affects my immune system's function.

Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%, Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing, Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m2, Hepatic: Serum conjugated (direct) bilirubin < 2.0 x ULN for age; AST and ALT < 5.0 x ULN for age, Karnofsky or Lansky (age-dependent) performance score ≥ 50, Signed written informed consent

I have a donor match for a transplant that matches at least half of the required genetic markers.

Exclusion Criteria

I have a sibling who matches my HLA type and can donate bone marrow, or I have a matched unrelated donor.

I have HIV or an uncontrolled infection.

Patient has received prior solid organ transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo TCR alpha beta and CD19 depleted stem cell transplantation using CliniMACS

Up to 100 days

Engraftment Monitoring

Monitoring of donor engraftment and chimerism, including platelet and neutrophil engraftment

Up to 42 days

Follow-up

Participants are monitored for safety, effectiveness, and complications such as GvHD and infections

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Haploidentical Hematopoietic Cell Transplantation

Trial Overview

The study tests a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cells from half-matched family donors to treat the underlying condition. The process involves collecting stem cells through peripheral blood or bone marrow and filtering them using an investigational device called CliniMACS.

How Is the Trial Designed?

Group I: TCR alpha beta T cell depletion Experimental Treatment 1 Intervention

The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol

Haploidentical Hematopoietic Cell Transplantation is already approved in United States, European Union for the following indications:

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

• Severe Aplastic Anemia
• Hematological Malignancies
• Immunodeficiency Disorders

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

• Severe Aplastic Anemia
• Acute Leukemia
• Chronic Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Johns Hopkins All Children's Hospital

Lead Sponsor

Trials

47

Recruited

5,009,000+

Published Research Related to This Trial

Hematopoietic Cell Transplantation (HCT) from HLA-haploidentical parental donors is a viable and readily available treatment option for infants with Severe Combined Immunodeficiency (SCID) when matched family donors are not available.

Successful HCT outcomes in SCID should consider not only survival rates but also the stability and function of the graft, as well as potential late complications from the disease or treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-haploidentical donor transplantation in severe combined immunodeficiency. Friedrich, W., Hönig, M.[2011]

Haploidentical hematopoietic stem cell transplant (HSCT) offers a promising alternative for patients lacking fully HLA-matched donors, with improved outcomes over the past decade.

Despite initial high mortality rates due to graft rejection and severe graft-versus-host disease, advancements in techniques have enhanced the safety and efficacy of haploidentical HSCT, making it a viable option for treating various hematologic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the progress on haploidentical hematopoietic transplantation. Farhadfar, N., Hogan, WJ.[2020]

Haploidentical stem cell transplantation (haploHCT) offers a life-saving option for high-risk sickle cell disease patients without matched donors, but it faces challenges like graft failure and graft-versus-host disease (GvHD).

Recent strategies, including T-cell depletion methods and post-transplant cyclophosphamide, aim to improve engraftment rates while minimizing GvHD, and achieving stable mixed chimerism post-transplant has shown promise for better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for patients with sickle cell disease: current status. Pawlowska, AB., Sun, V., Rosenthal, J.[2022]

Haploidentical hematopoietic stem cell transplantation (HCT) with post-transplantation cyclophosphamide (haplo-PTCy) is a feasible treatment option for children with primary immunodeficiency diseases (PID), showing a 66% overall survival rate after 2 years, including 64% for severe combined immunodeficiency (SCID) patients.

The procedure demonstrated a high cumulative incidence of neutrophil recovery (88% in SCID and 84% in non-SCID patients), but also a notable risk of acute graft-versus-host disease (GVHD), with 33% of patients experiencing grade II-IV GVHD within 100 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases. Fernandes, JF., Nichele, S., Arcuri, LJ., et al.[2021]

Hematopoietic Cell Transplantation (HCT) from HLA-haploidentical parental donors is a viable and readily available treatment option for infants with Severe Combined Immunodeficiency (SCID) when matched family donors are not available.

Successful HCT not only focuses on survival rates but also emphasizes the importance of graft stability, function, and monitoring for potential late complications related to both the disease and the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-haploidentical donor transplantation in severe combined immunodeficiency. Friedrich, W., Hönig, M.[2011]

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]

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]

A nationwide study of 566 patients in Japan showed that hematopoietic cell transplantation (HCT) for non-SCID inborn errors of immunity has a 10-year overall survival rate of 74% and an event-free survival rate of 64%.

HCT from unrelated bone marrow (URBM) and matched sibling donors (MSD) had comparable survival rates (79% and 81%, respectively), while unrelated cord blood (URCB) had a lower survival rate of 69% but was still a common option, indicating its potential as an alternative donor source.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985-2016. Miyamoto, S., Umeda, K., Kurata, M., et al.[2022]

Reduced toxicity conditioning regimens for hematopoietic cell transplantation (HCT) in children with primary immunodeficiencies (PID) have significantly improved transplant outcomes, reducing acute toxicities and transplant-related mortality.

Treosulfan has shown promise as a preparative agent, and the use of peripheral stem cells has been linked to better donor chimerism, making reduced toxicity conditioning the new standard of care for patients with PID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. Lum, SH., Hoenig, M., Gennery, AR., et al.[2020]

Citations

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pmc.ncbi.nlm.nih.gov

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A multicenter study reported outcome of HSCT in 76 patients with RAG deficiency (37). In this study, survival was ~80% for 25 patients who ...

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Outcomes after Haploidentical Stem Cell Transplantation ...

The majority of patients reached 200/μL CD4+ and 1000/μL CD3+ cell counts between 3 and 6 months; 17 of 40 patients with available data and alive at 100 days ...

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The most common indications for HSCT were SCID, Wiskott-Aldrich syndrome, and chronic granulomatous disease. Five-year overall survival (OS) was 72 % for the ...

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Outcomes in the entire cohort showed a 3-year overall survival, event-free survival (EFS), and grade 3 to 4 graft-versus-host disease (GVHD)– ...

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pmc.ncbi.nlm.nih.gov/articles/PMC7100782/

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Overall mortality was found to be 37.5% with overall survival of 62.5% with a median follow-up of 23.3 months. In resource limited settings, PTCy has the ...

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astctjournal.org

astctjournal.org/article/S2666-6367(25)01408-3/fulltext

Efficacy and Safety of Haploidentical Hematopoietic Stem ...

Haplo-HSCT combined with UCB infusion is a safe and effective strategy for patients lacking young donors, offering rapid hematopoietic recovery, ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2666636725014083

Efficacy and safety of haploidentical hematopoietic stem ...

Haplo-HSCT combined with UCB infusion is a safe and effective strategy for patients lacking young donors, offering rapid hematopoietic recovery, ...

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frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1495666/full

Haploidentical stem cell transplantation with posttransplant ...

The Primary Immune Deficiency Treatment Consortium in the United States reported an overall survival rate of 91% at 5 years (2), whereas the ...