- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04414046
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jade Hanson, MSN
- Phone Number: 7277676468
- Email: jade.hanson@jhmi.edu
Study Locations
-
-
Florida
-
Saint Petersburg, Florida, United States, 33701
- Recruiting
- Johns Hopkins All Children's Hospital
-
Contact:
- Ian Snyder
- Email: ISnyder5@jhmi.edu
-
Principal Investigator:
- Deepak Chellapandian, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TCR alpha beta T cell depletion
The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol
|
TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Day 100 after transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 |
Up to 2 years post transplant
|
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
|
Up to 42 days post transplant
|
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.
|
Up to 42 days post transplant
|
Transplant-related mortality
Time Frame: Up to 100 days post transplant
|
Rate of transplant-related mortality
|
Up to 100 days post transplant
|
Acute grade II-IV GvHD
Time Frame: Up to 2 years post transplant
|
Incidence and severity of acute graft versus host disease
|
Up to 2 years post transplant
|
Chronic GvHD
Time Frame: Up to 2 years post transplant
|
Incidence and severity of chronic graft versus host disease
|
Up to 2 years post transplant
|
Primary graft failure
Time Frame: Up to 2 years post transplant
|
Rates of primary graft failure
|
Up to 2 years post transplant
|
Secondary graft failure
Time Frame: Up to 2 years post transplant
|
Rates of secondary graft failure
|
Up to 2 years post transplant
|
Transplant-related complications
Time Frame: Up to 2 years post transplant
|
Frequency of transplant-related complications following transplantation
|
Up to 2 years post transplant
|
Transplant-related infections
Time Frame: Up to 2 years post transplant
|
Frequency of transplant-related infections following transplantation
|
Up to 2 years post transplant
|
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+)
|
Up to 2 years post transplant
|
Collaborators and Investigators
Investigators
- Principal Investigator: Deepak Chellapandian, MD, Johns Hopkins All Children's Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HAP-PID
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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