Hematopoietic Stem Cell Transplantation for Patients With Severe Sickle Cell Disease Using Myeloablative Conditioning and αβ+ T-cell Depleted Hematopoietic Stem Cells From Partially Matched Familial Donors

University of Chicago1 site in 1 country3 target enrollmentApril 7, 2020

ConditionsSickle Cell Disease

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Sickle Cell Disease
Sponsor: University of Chicago
Enrollment: 3
Locations: 1
Primary Endpoint: 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
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

April 7, 2020

End Date

May 22, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

University of Chicago

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
•Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
•Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
•Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
•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

•Karnofsky or Lansky score \< 60%
•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
•Severe renal impairment (as evidenced by creatinine clearance of \<50ml/minute glomerular filtration rate (GFR) \< 50% predicted normal)
•Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
•Pregnant Female.
•Lactating female.
•Pulmonary function with baseline O2 saturation \<85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO \<40%.

Outcomes

Primary Outcomes

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

Time Frame: 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 Outcomes

Estimate 1-year Overall and Event-free Survival After Hap-HSCT(1 year post transplant)
Observe the Incidence of Grades I Through IV Acute GvHD(100 days post transplant)
Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV(100 days post transplant)
Observe the Incidence of Grades I Through IV Chronic GvHD(1 year post transplant)
Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV(1 year post transplant)