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

NCT04207320 | Terminated Results DMC FDA Device

• 1 other identifier: IRB19-0640
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Stage I

EXPERIMENTAL

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

Device: αβ+ T-cell depletion with Miltenyi CliniMACS system

Stage II

EXPERIMENTAL

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

Device: αβ+ T-cell depletion with Miltenyi CliniMACS system

Interventions

αβ+ T-cell depletion with Miltenyi CliniMACS system 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 I; Stage II

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. John Cunningham
• Organization: University of Chicago

jcunning@bsd.uchicago.edu

773-702-6808

Study Officials

• John Cunningham, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 20, 2019
• Study Start: April 7, 2020
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: December 4, 2024
• Results First Posted: December 4, 2024

Record last verified: 2024-11

Locations

US (1)