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HaploSCD: Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease

Sponsor
New York Medical College (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01461837
Collaborator
UCSF Benioff Children's Hospital Oakland (Other), Medical College of Wisconsin (Other), Washington University School of Medicine (Other), Tufts Medical Center (Other), University of California, San Francisco (Other), University of California, Los Angeles (Other), Miltenyi Biomedicine GmbH (Industry), Ann & Robert H Lurie Children's Hospital of Chicago (Other)
21
Enrollment
6
Locations
1
Arm
167
Duration (Months)
3.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being done to determine the safety and outcome (long-term control) of a high-dose chemotherapy regimen followed by an infusion of CD34 selected (immune cells) stem cells from a partially matched adult family member donor, called haploidentical stem cell transplantation, in high-risk sickle cell disease patients.

Funding Source - FDA OOPD

Condition or Disease Intervention/Treatment Phase
  • Drug: CD34 selected T-cell depleted allogeneic SCT
 Phase 2

Detailed Description

The purpose of this study is to investigate host myeloimmunosuppressive conditioning followed by familial haploidentical T cell depleted allogeneic stem cell transplantation in patients with high risk Sickle Cell Disease (SCD). It is hypothesized that it will be safe and well tolerated, and result in sustained donor chimerism, acceptable engraftment and immune reconstitution. Also, that it will limit SCD related organ damage resulting in improved and/or stable neurological, neurocognitive, pulmonary and pulmonary vascular function and health related quality of life (QOL).

Patients 2-20.99 years of age with a diagnosis of high-risk SCD and with an unaffected HLA partially matched family donor and meeting eligibility criteria (inclusion and exclusion criteria) are eligible.

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)
Study Start Date :
Jan 1, 2012
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Haplo Stem Cell Transplantation

CD34 selected T-cell depleted allogeneic SCT

Drug: CD34 selected T-cell depleted allogeneic SCT
Hydroxyurea (60 mg/kg/day) and azathioprine (3 mg/kg/day) day -59 to day -11; fludarabine (30 mg/m2) Days -17, -16, -15, -14, -13; busulfan (3.2 mg/kg/day) Days -12, -11, -10, -9; thiotepa (10 mg/kg IV) day -8; cyclophosphamide (50 mg/kg) Days -7, -6, -5, -4; TLI on day -3; rabbit ATG (2.0 mg/kg/day) day -5,-4,-3, and -2; Stem Cell infusion day 0
Other Names:
  • Familial haploidentical
  • T-cell depleted
  • allogeneic stem cell transplantation
  • high risk Sickle Cell Disease

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Treatment related events [1 year]

      Death, primary or late graft rejection, or recurrence of disease and acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease

    Secondary Outcome Measures

    1. neurological/neurocognitive status [2 years]

      Change from baseline in neurological/neurocognitive status

    2. Pulmonary/pulmonary vascular status [2 years]

      Change from baseline of Pulmonary/pulmonary vascular status

    3. Health-related quality of life [4 years]

      Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 20 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Homozygous Hemoglobin S Disease, or Hemoglobin S Beta0/+ thalassemia

    • Patients must demonstrate one or more of the following Sickle Cell Disease Complications

    1. Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI

    2. Minimum of two episodes of acute chest syndrome.

    3. Recurrent painful events (at least 3 in the 2 years prior to enrollment).

    4. Abnormal TCD study requiring starting on chronic transfusion therapy.

    5. At least one silent infarct lesion on a MRI scan of the head.

    • A familial haploidentical donor without homozygous sickle cell disease

    • Adequate organ function (renal, liver, cardiac and pulmonary function)

    • Karnofsky or Lansky (age appropriate) Performance Score ≥50%

    • Liver biopsy is optional to assess for iron overload in chronically transfused patients.

    Exclusion Criteria:

    • Females who are pregnant or breast-feeding

    • SCD Patients with documented uncontrolled infection

    • SCD patients who have an unaffected HLA matched family donor willing to proceed to donation

    • Karnofsky/Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)

    • Demonstrated lack of compliance with medical care.

    • Clinically significant fibrosis or cirrhosis of the liver

    • Previously received a HSCT

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California Los Angeles (UCLA) Los Angeles California United States 90095
    2 Children's Hospital and Research Center Oakland Oakland California United States 94609
    3 Lurie Children's Hospital Chicago Illinois United States 60611-2605
    4 Washington University/St. Louis Children's Hospital Saint Louis Missouri United States 63110
    5 New York Medical College Valhalla New York United States 10595
    6 Medical College of Wisconsin/Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • New York Medical College
    • UCSF Benioff Children's Hospital Oakland
    • Medical College of Wisconsin
    • Washington University School of Medicine
    • Tufts Medical Center
    • University of California, San Francisco
    • University of California, Los Angeles
    • Miltenyi Biomedicine GmbH
    • Ann & Robert H Lurie Children's Hospital of Chicago

    Investigators

    • Principal Investigator: Mitchell S Cairo, MD, New York Medical College

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Mitchell Cairo, Principal Investigator, New York Medical College
    ClinicalTrials.gov Identifier:
    NCT01461837
    Other Study ID Numbers:
    • NYMC526-4090
    • FD-R-0004090
    First Posted:
    Oct 28, 2011
    Last Update Posted:
    May 27, 2021
    Last Verified:
    May 1, 2021
    Keywords provided by Mitchell Cairo, Principal Investigator, New York Medical College
    sickle cell disease
    stem cell transplantation
    haploidentical
    Additional relevant MeSH terms:
    Anemia, Sickle Cell

    Study Results

    No Results Posted as of May 27, 2021