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

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

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).

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Device: αβ+ T-cell depletion with Miltenyi CliniMACS system

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	100 days post-Hap-HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate 1-year Overall and Event-free Survival After Hap-HSCT	Proportion of patients at 1 year who have not died or had graft failure	1 year post transplant
Observe the Incidence of Grades I Through IV Acute GvHD	Proportion of subjects with grades I through IV acute GvHD	100 days post transplant
Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV	Proportion of subjects with grades III through IV acute GvHD	100 days post transplant
Observe the Incidence of Grades I Through IV Chronic GvHD	Proportion of subjects with grades I through IV chronic GvHD	1 year post transplant
Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV	Proportion of subjects with grades III through IV chronic GvHD	1 year post transplant

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: John Cunningham, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2020
• Primary Completion (Actual): May 22, 2023
• Study Completion (Actual): May 22, 2023

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: IRB19-0640

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes