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

Primary Purpose

Sickle Cell Disease

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

αβ+ T-cell depletion with Miltenyi CliniMACS system

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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%.

Sites / Locations

The University of ChicagoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Stage I

Stage II

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Observe the incidence of grades I through IV acute GvHD

Proportion of subjects with grades I through IV acute GvHD

Observe incidence of severe acute GvHD as defined by grades III through IV

Proportion of subjects with grades III through IV acute GvHD

Observe the incidence of grades I through IV chronic GvHD

Proportion of subjects with grades I through IV chronic GvHD

Observe incidence of severe chronic GvHD as defined by grades III and IV

Proportion of subjects with grades III through IV chronic GvHD

Full Information

NCT ID

NCT04207320

First Posted

December 11, 2019

Last Updated

May 11, 2023

Sponsor

University of Chicago

1. Study Identification

Unique Protocol Identification Number

NCT04207320

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 7, 2020 (Actual)

Primary Completion Date

November 2027 (Anticipated)

Study Completion Date

November 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Stage I

Arm Type

Experimental

Arm Description

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

Arm Title

Stage II

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

αβ+ T-cell depletion with Miltenyi CliniMACS system

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

100 days post-Hap-HSCT

Secondary Outcome Measure Information:

Title

Estimate 1-year overall and event-free survival after Hap-HSCT

Description

Proportion of patients at 1 year who have not died or had graft failure

Time Frame

1 year post transplant

Title

Observe the incidence of grades I through IV acute GvHD

Description

Proportion of subjects with grades I through IV acute GvHD

Time Frame

100 days post transplant

Title

Observe incidence of severe acute GvHD as defined by grades III through IV

Description

Proportion of subjects with grades III through IV acute GvHD

Time Frame

100 days post transplant

Title

Observe the incidence of grades I through IV chronic GvHD

Description

Proportion of subjects with grades I through IV chronic GvHD

Time Frame

1 year post transplant

Title

Observe incidence of severe chronic GvHD as defined by grades III and IV

Description

Proportion of subjects with grades III through IV chronic GvHD

Time Frame

1 year post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

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%.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rebecca Puplava

Phone

773-702-2879

rpuplava@peds.bsd.uchicago.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Cunningham, MD

Organizational Affiliation

University of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shelby Gruntorad, MS

Phone

773-702-6554

sgruntorad@peds.bsd.uchicago.edu

12. IPD Sharing Statement

Learn more about this trial

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

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