Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT04207320
• Recruitment Status: Recruiting
• First Posted: December 20, 2019
• Last Update Posted: May 15, 2023
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Tracking Information

• First Submitted Date: December 11, 2019
• First Posted Date: December 20, 2019
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: April 7, 2020
• Estimated Primary Completion Date: November 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 19, 2019)

• Estimate 1-year overall and event-free survival after Hap-HSCT [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 100 days post transplant ]
  Proportion of subjects with grades III through IV acute GvHD
• Observe the incidence of grades I through IV chronic GvHD [ Time Frame: 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 [ Time Frame: 1 year post transplant ]
  Proportion of subjects with grades III through IV chronic GvHD

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

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.

Study Arms

• Experimental: Stage I
  Stage I will include eligible subjects between the ages of 10-25 years.
  Intervention: Device: αβ+ T-cell depletion with Miltenyi CliniMACS system
• Experimental: Stage II
  Stage II will include eligible subjects between the ages of 2-25 years.
  Intervention: Device: αβ+ T-cell depletion with Miltenyi CliniMACS system

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 19, 2019): 38
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2027
• Estimated Primary Completion Date: November 2027 (Final data collection date for primary outcome measure)

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%.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rebecca Puplava; 773-702-2879; rpuplava@peds.bsd.uchicago.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04207320
• Other Study ID Numbers: IRB19-0640
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Chicago
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Chicago
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Cunningham, MD; University of Chicago

• PRS Account: University of Chicago
• Verification Date: May 2023