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

NCT ID: NCT04207320

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-07
• Study Completion Date: 2023-05-22

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).

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage I

Stage I will include eligible subjects between the ages of 10-25 years.

Group Type: EXPERIMENTAL

αβ+ T-cell depletion with Miltenyi CliniMACS system

Intervention Type: DEVICE

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.

Stage II

Stage II will include eligible subjects between the ages of 2-25 years.

Group Type: EXPERIMENTAL

αβ+ T-cell depletion with Miltenyi CliniMACS system

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

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%.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Cunningham, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

The University of Chicago

Chicago, Illinois, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB19-0640

Identifier Type: -

Identifier Source: org_study_id