Status:
RECRUITING
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
Lead Sponsor:
Johns Hopkins All Children's Hospital
Conditions:
Hemoglobinopathy (Disorder)
Severe Aplastic Anemia
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE2
Brief Summary
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 ...
Eligibility Criteria
Inclusion
- Severe sickle cell disease (HbSS, HbSC, HbSB0, HbSB+, HbSD, HbSE) with at least one of the following criteria:
- Cerebrovascular accident lasting longer than 24 hours
- Impaired neuropsychological function with abnormal brain MRI/MRA
- Patients with frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes
- Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy
- Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes yearly for 3 years and have failed treatment with hydroxyurea (HU) (at least 6 months on maximum tolerated dose) or who are intolerant to HU therapy
- Thalassemia major with at least one of the following criteria:
- Transfusion dependency defined as receiving 8 or more transfusions per year
- Thalassemia diagnosis documented by clinical assessment, laboratory evidence with microcytic anemia and absence of HbA (\< 10%) on electrophoresis and or confirmation by DNA analysis of alpha and beta gene loci
- Genotypically proven thalassemia major for children \< 2 years of age even in the absence of transfusion dependency
- Lucarelli class 1 or 2 risk status (i.e. with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor response to chelation therapy)
- Bone marrow failure syndromes and autoimmune cytopenias:
- Severe Aplastic Anemia refractory to immunosuppressive therapy
- Diamond Blackfan Anemia refractory to conventional therapy
- Inherited Bone Marrow Failure Syndromes such as Fanconi anemia and Shwachman-Diamond syndrome with progressive marrow failure (without cytogenetic evidence of MDS/AML)
- Severe Congenital Neutropenia
- Congenital Amegakaryocytic Thrombocytopenia
- Glanzmann Thrombasthenia
- Autoimmune Cytopenias refractory to conventional treatment (including Pure red cell aplasia, Evan's syndrome, Immune thrombocytopenia, autoimmune hemolytic anemia)
- Other marrow failure disorders not otherwise specified
- 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 as per local laboratory unless attributable to Gilbert's syndrome; AST and ALT \< 5.0 x ULN for age as per local laboratory. Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or a profound change in serum hemoglobin post blood transfusion, are not excluded.
- Karnofsky or Lansky (age-dependent) performance score ≥ 50
- Signed written informed consent
Exclusion
- 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.
- For patients with hemoglobinopathy, liver biopsy is necessary if the patient has received chronic transfusions for over a year and has two ferritin levels of ≥ 1000 ng/ml. Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.
Key Trial Info
Start Date :
July 22 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 30 2026
Estimated Enrollment :
17 Patients enrolled
Trial Details
Trial ID
NCT04356469
Start Date
July 22 2020
End Date
June 30 2026
Last Update
June 24 2025
Active Locations (1)
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1
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States, 33701