Haploidentical HCT for Primary Immunodeficiency
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Johns Hopkins All Children's Hospital
Disqualifiers: Pregnancy, HIV, Uncontrolled infections, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
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.
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%.
12345Is 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.
34678How 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.
23459Eligibility 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
+2 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: TCR alpha beta T cell depletionExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins All Children's HospitalSaint Petersburg, FL
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Who Is Running the Clinical Trial?
Johns Hopkins All Children's HospitalLead Sponsor
References
Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases. [2021]Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/μL CD4+ and 1000/μL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
[Hematopoietic stem cell transplantation in children with primary immunodeficiencies]. [2009]Hematopoietic stem cell transplantation is the optimal treatment for patients with primary immunodeficiencies. Best results are achieved with stem cells from a HLA-identical donor, but it is only possible in a small number of patients. Until recently, HLA-mismatched/haploidentical hematopoietic stem cell transplantation was reserved exclusively for patients with severe combined immunodeficiency (SCID). However, as there are many haploidentical donors, it has become the treatment of choice for many other severe primary immunodeficiencies. Apart from appropriate choice of the donor, treatment of infections and pre-transplantation patient conditioning have major impact on transplantation outcome in patients with primary immunodeficiencies.
HLA-haploidentical donor transplantation in severe combined immunodeficiency. [2011]Curative treatment of Severe Combined Immunodeficiency (SCID) by Hematopoietic Cell Transplantation (HCT) remains a challenge, in particular in infants presenting with serious, poorly controllable complications. In the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a uniformly and readily available treatment option, offering a high chance to be successful. Concerning outcomes of HCT in SCID, other important parameters beside survival need to be taken into consideration, in particular the stability and robustness of the graft and its function, as well as potential late complications, related either to the disease or to the treatment.
HLA-haploidentical donor transplantation in severe combined immunodeficiency. [2011]Curative treatment of Severe Combined Immunodeficiency (SCID) by Hematopoietic Cell Transplantation (HCT) remains a challenge, in particular in infants presenting with serious, poorly controllable complications. In the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a uniformly and readily available treatment option, offering a high chance to be successful. Concerning outcomes of HCT in SCID, other important parameters beside survival need to be taken into consideration, in particular the stability and robustness of the graft and its function, as well as potential late complications, related either to the disease or to the treatment.
Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. [2019]Hematopoietic stem-cell transplantation is the treatment of choice for severe primary T-cell immunodeficiencies. When an HLA-identical sibling donor is not available, an alternative donor stem-cell source is needed. In primary T-cell immunodeficiencies, T-cell-depleted HLA-haploidentical bone marrow transplantation has been particularly successful in reconstituting the T-cell immune system in many of the severe combined immunodeficiency syndrome types. However, there are some problems associated with this preparation as a stem donor source, such as increased resistance to engraftment, a long period of time for T-cell engraftment to occur, and failure to engraft B cells and B-cell functions. These problems can be especially troublesome if the patient is infected before the transplantation.
Haploidentical stem cell transplantation for patients with sickle cell disease: current status. [2022]For patients with high-risk sickle cell disease (SCD) without any available matched sibling or unrelated donor, haploidentical stem cell transplantation (haploHCT) expands the availability of this life-saving intervention to nearly all patients who may benefit from HCT. The greatest challenge in haploHCT has been the significant risk of graft failure. Developing a treatment modality which sustains engraftment without increasing the incidence of debilitating graft-versus-host disease (GvHD) remains the ultimate goal. A number of modifications have been explored to overcome the high incidence of graft rejection and severe GvHD including: (1) ex-vivo T-cell depletion (via CD34+ selection, CD3+/CD19+, or TCRαβ+/CD19+ depletion), and (2) in vivo T-cell depletion using unmanipulated grafts followed by post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis. Furthermore, the presence of donor-specific anti-HLA antibodies (DSA) has been associated with an increased risk of both graft failure and poor graft function. Several approaches for desensitization ameliorate this risk when a suitable donor without DSA is not available. In addition to advances in supportive care, the recent demonstration that stable mixed chimerism post-HCT sufficiently sustains symptom-free status has opened the door for less toxic treatment approaches yielding excellent survival outcomes. Though late effects remain uncertain, the goal of finding the least toxic conditioning regimen while providing the highest rate of donor engraftment draws closer within reach. In this review, the authors aim to present the latest findings, challenges, and treatment modalities of this life-saving modality.
Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985-2016. [2022]Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan.
Overview of the progress on haploidentical hematopoietic transplantation. [2020]Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLA-matched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor, umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graft-versus-host disease caused by major donor-recipient HLA-disparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.
Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. [2020]Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID.