TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children
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|ClinicalTrials.gov Identifier: NCT04414046|
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : September 15, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Primary Immune Deficiency Disorders Metabolic Disease||Biological: Haploidentical Hematopoietic Cell Transplantation||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children|
|Actual Study Start Date :||July 22, 2020|
|Estimated Primary Completion Date :||June 2024|
|Estimated Study Completion Date :||June 2024|
Experimental: TCR alpha beta T cell depletion
The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol
Biological: Haploidentical Hematopoietic Cell Transplantation
TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
- Incidence of successful donor engraftment [ Time Frame: Day 100 after transplantation ]The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), > 95%=full donor chimerism.
- Overall survival and Event-free survival [ Time Frame: Up to 2 years post transplant ]
Overall survival is defined as the time of enrollment to death from any cause or last follow up.
Event-free survival is defined as the time of enrollment to death, primary or secondary graft failure, graft failure necessitating a second HCT procedure, DLI or stem cell boost given for treatment of falling chimerism, or disease recurrence
- Kinetics of neutrophil engraftment [ Time Frame: Up to 42 days post transplant ]Neutrophil engraftment defined as absolute neutrophil count ≥500/μL for 3 consecutive measurements on different days
- Kinetics of platelet engraftment [ Time Frame: Up to 42 days post transplant ]Platelet engraftment defined as sustained platelet count >20,000/μL and >50,000//μL with no platelet transfusions in the preceding seven days.
- Transplant-related mortality [ Time Frame: Up to 100 days post transplant ]Rate of transplant-related mortality
- Acute grade II-IV GvHD [ Time Frame: Up to 2 years post transplant ]Incidence and severity of acute graft versus host disease
- Chronic GvHD [ Time Frame: Up to 2 years post transplant ]Incidence and severity of chronic graft versus host disease
- Primary graft failure [ Time Frame: Up to 2 years post transplant ]Rates of primary graft failure
- Secondary graft failure [ Time Frame: Up to 2 years post transplant ]Rates of secondary graft failure
- Transplant-related complications [ Time Frame: Up to 2 years post transplant ]Frequency of transplant-related complications following transplantation
- Transplant-related infections [ Time Frame: Up to 2 years post transplant ]Frequency of transplant-related infections following transplantation
- Cellular and Immunological reconstitution by laboratory evaluations [ Time Frame: Up to 2 years post transplant ]The recovery of different lymphocyte subpopulation (CD3+; CD4+; CD8+; CD3+CD45RA+and CD45RO; TCR alpha beta; TCR gamma delta; CD19+)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||up to 21 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Patient with any form of primary immune deficiency/dysregulatory disorders characterized by aberrant immune function, abnormal hematopoiesis, systemic or organ specific autoimmunity and/or non-malignant lymphoproliferation. This includes, but not limited to:
I. Disorders of phagocytes: Chronic granulomatous disease, Leukocyte adhesion deficiency, defects of IL-10 pathway, MonoMac syndrome
II. Defects of cellular and humoral immunity: Severe Combined Immunodeficiency Disorder (infants with classic SCID up to 2 years of age will be excluded due to other open protocol), X-linked hyper-IgM syndrome, DOCK8 deficiency, ZAP70 deficiency, common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, NEMO deficiency.
III. Disorder of immune dysregulation: Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, CTLA4 deficiency, LRBA deficiency, STAT1 GOF, STAT3 GOF, X-linked lymphoproliferative disease etc.
IV. Other PIDs and immune dysregulatory disorders who can be benefitted by HCT as deemed appropriate by the PI and the treating immunologist.
- Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes of hyper inflammation) and multisystem refractory Langerhans cell histiocytosis.
- Metabolic disorders that could improve or stabilize after stem cell transplantation such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.
- Patient has a suitable genotypic identical match of 5/10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.
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
- Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
- Pregnant or breastfeeding females.
- Patient has HIV or uncontrolled fungal, bacterial or viral infections.
- Patient has received prior solid organ transplant.
- Patient has active GVHD (> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04414046
|Contact: Jade Hanson, MSNfirstname.lastname@example.org|
|United States, Florida|
|Johns Hopkins All Children's Hospital||Recruiting|
|Saint Petersburg, Florida, United States, 33701|
|Contact: Ian Snyder email@example.com|
|Principal Investigator: Deepak Chellapandian, MD|
|Principal Investigator:||Deepak Chellapandian, MD||Johns Hopkins All Children's Hospital|
|Responsible Party:||Johns Hopkins All Children's Hospital|
|Other Study ID Numbers:||
|First Posted:||June 4, 2020 Key Record Dates|
|Last Update Posted:||September 15, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Primary Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Genetic Diseases, Inborn