Haploidentical HCT for Primary Immunodeficiency

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

Trial Summary

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 data supports the effectiveness of the treatment Haploidentical Hematopoietic Cell Transplantation for Primary Immunodeficiency?

Haploidentical Hematopoietic Cell Transplantation (HaploHCT) is effective for treating primary immunodeficiencies, especially when a matched donor is unavailable. Studies show that it can cure about two-thirds of children with these conditions, with a 2-year survival rate of around 66%. ^{1 2 3 4 5}

Is haploidentical hematopoietic cell transplantation generally safe for humans?

Haploidentical hematopoietic cell transplantation (HaploHCT) has been associated with challenges like graft rejection and graft-versus-host disease (GvHD, where the donor cells attack the recipient's body), but recent advances have improved safety and outcomes. Techniques like T-cell depletion and post-transplant cyclophosphamide have been developed to reduce these risks, making the procedure safer over time. ^{3 4 6 7 8}

How is Haploidentical Hematopoietic Cell Transplantation different from other treatments for primary immunodeficiency?

Haploidentical Hematopoietic Cell Transplantation is unique because it allows for the use of stem cells from a partially matched family donor, making it more accessible for patients who do not have a fully matched donor. This treatment has become the preferred option for many severe primary immunodeficiencies due to the availability of haploidentical donors and its success in reconstituting the immune system. ^{2 3 4 5 9}

What is the purpose of this trial?

This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.

Research Team

Deepak Chellapandian, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

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

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases. [2021]

2. Croatia pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cell transplantation in children with primary immunodeficiencies]. [2009]

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

HLA-haploidentical donor transplantation in severe combined immunodeficiency. [2011]

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

HLA-haploidentical donor transplantation in severe combined immunodeficiency. [2011]

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

Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for patients with sickle cell disease: current status. [2022]

7. Netherlands 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. [2022]

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

Overview of the progress on haploidentical hematopoietic transplantation. [2020]

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

Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. [2020]