Clinical trial NCT04207320: Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Sickle Cell Disease
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2019-12-20
Enrollment: 3
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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%.

Primary outcomes:
measure: 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
timeFrame: 100 days post-Hap-HSCT
Secondary outcomes:
measure: Estimate 1-year Overall and Event-free Survival After Hap-HSCT
timeFrame: 1 year post transplant
measure: Observe the Incidence of Grades I Through IV Acute GvHD
timeFrame: 100 days post transplant
measure: Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV
timeFrame: 100 days post transplant
measure: Observe the Incidence of Grades I Through IV Chronic GvHD
timeFrame: 1 year post transplant
measure: Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV
timeFrame: 1 year post transplant
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: John Cunningham, MD
role: PRINCIPAL_INVESTIGATOR
References: