Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease
Study Details
Study Description
Brief Summary
The purpose of this study is to develop a safe and curative stem cell transplant approach to treating sickle cell disease by assessing the safety of haploidentical hematopoietic stem cell transplantation using αβ+ T-cell depletion for children and adolescents with severe sickle cell disease (SCD).
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Stage I Stage I will include eligible subjects between the ages of 10-25 years. |
Device: αβ+ T-cell depletion with Miltenyi CliniMACS system
Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.
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Experimental: Stage II Stage II will include eligible subjects between the ages of 2-25 years. |
Device: αβ+ T-cell depletion with Miltenyi CliniMACS system
Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.
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Outcome Measures
Primary Outcome Measures
- Safety, as measured by incidence of graft failure, grade III/IV irreversible end organ toxicity, grade III/IV aGvHD, or death within 100 days post-Hap-HSCT [100 days post-Hap-HSCT]
Graft Function: efficacy is defined as stable donor engraftment (>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (<50% HbS in the peripheral blood). Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT
Secondary Outcome Measures
- Estimate 1-year overall and event-free survival after Hap-HSCT [1 year post transplant]
Proportion of patients at 1 year who have not died or had graft failure
- Observe the incidence of grades I through IV acute GvHD [100 days post transplant]
Proportion of subjects with grades I through IV acute GvHD
- Observe incidence of severe acute GvHD as defined by grades III through IV [100 days post transplant]
Proportion of subjects with grades III through IV acute GvHD
- Observe the incidence of grades I through IV chronic GvHD [1 year post transplant]
Proportion of subjects with grades I through IV chronic GvHD
- Observe incidence of severe chronic GvHD as defined by grades III and IV [1 year post transplant]
Proportion of subjects with grades III through IV chronic GvHD
Eligibility Criteria
Criteria
Inclusion Criteria:
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Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
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Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
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Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
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Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
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SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within [two years] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease.
Exclusion Criteria:
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Karnofsky or Lansky score < 60%
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Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient has been on chronic transfusion therapy > 6 months or has a ferritin > 1000 ng/ml) or AST or ALT >5 times the upper limit of normal
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Severe renal impairment (as evidenced by creatinine clearance of <50ml/minute glomerular filtration rate (GFR) < 50% predicted normal)
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Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
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Pregnant Female.
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Lactating female.
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Pulmonary function with baseline O2 saturation <85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO <40%.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The University of Chicago | Chicago | Illinois | United States | 60637 |
Sponsors and Collaborators
- University of Chicago
Investigators
- Principal Investigator: John Cunningham, MD, University of Chicago
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB19-0640