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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04207320
Recruitment Status : Recruiting
First Posted : December 20, 2019
Last Update Posted : December 20, 2019
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Device: αβ+ T-cell depletion with Miltenyi CliniMACS system Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : November 2027
Estimated Study Completion Date : November 2027

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  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 [ 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



Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hemoglobin SS, SC or S-β0 Thalassemia 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 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 ACS 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%.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04207320


Contacts
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Contact: Shelby Gruntorad, MS 7737026554 sgruntorad@peds.bsd.uchicago.edu

Locations
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United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Shelby Gruntorad, MS    773-702-6554    sgruntorad@peds.bsd.uchicago.edu   
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: John Cunningham, MD University of Chicago
Principal Investigator: Michele Nassin, MD University of Chicago

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT04207320    
Other Study ID Numbers: IRB19-0640
First Posted: December 20, 2019    Key Record Dates
Last Update Posted: December 20, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn