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

Primary Purpose

Sickle Cell Disease

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CD34 selected T-cell depleted allogeneic SCT
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, stem cell transplantation, haploidentical

Eligibility Criteria

2 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California Los Angeles (UCLA)
  • Children's Hospital and Research Center Oakland
  • Lurie Children's Hospital
  • Washington University/St. Louis Children's Hospital
  • New York Medical College
  • Medical College of Wisconsin/Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Haplo Stem Cell Transplantation

Arm Description

CD34 selected T-cell depleted allogeneic SCT

Outcomes

Primary Outcome Measures

Treatment related events
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

neurological/neurocognitive status
Change from baseline in neurological/neurocognitive status
Pulmonary/pulmonary vascular status
Change from baseline of Pulmonary/pulmonary vascular status
Health-related quality of life
Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)

Full Information

First Posted
October 19, 2011
Last Updated
March 21, 2023
Sponsor
New York Medical College
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT01461837
Brief Title
Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease
Acronym
HaploSCD
Official Title
Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
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

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
sickle cell disease, stem cell transplantation, haploidentical

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Haplo Stem Cell Transplantation
Arm Type
Experimental
Arm Description
CD34 selected T-cell depleted allogeneic SCT
Intervention Type
Drug
Intervention Name(s)
CD34 selected T-cell depleted allogeneic SCT
Other Intervention Name(s)
Familial haploidentical, T-cell depleted, allogeneic stem cell transplantation, high risk Sickle Cell Disease
Intervention Description
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
Primary Outcome Measure Information:
Title
Treatment related events
Description
Death, primary or late graft rejection, or recurrence of disease and acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease
Time Frame
1 year
Secondary Outcome Measure Information:
Title
neurological/neurocognitive status
Description
Change from baseline in neurological/neurocognitive status
Time Frame
2 years
Title
Pulmonary/pulmonary vascular status
Description
Change from baseline of Pulmonary/pulmonary vascular status
Time Frame
2 years
Title
Health-related quality of life
Description
Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Homozygous Hemoglobin S Disease, or Hemoglobin S Beta0/+ thalassemia Patients must demonstrate one or more of the following Sickle Cell Disease Complications Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI Minimum of two episodes of acute chest syndrome. Recurrent painful events (at least 3 in the 2 years prior to enrollment). Abnormal TCD study requiring starting on chronic transfusion therapy. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell S Cairo, MD
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Children's Hospital and Research Center Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Lurie Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Facility Name
Washington University/St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Medical College of Wisconsin/Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35110690
Citation
Parsons SK, Rodday AM, Weidner RA, Morris E, Braniecki S, Shenoy S, Talano JA, Moore TB, Panarella A, Flower A, Milner J, Fabricatore S, Mahanti H, van de Ven C, Shi Q, Cairo MS. Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant. Bone Marrow Transplant. 2022 Apr;57(4):586-592. doi: 10.1038/s41409-022-01584-y. Epub 2022 Feb 2.
Results Reference
derived
Links:
URL
http://www.sicklecelltransplantconsortium.org/
Description
Consortium website for Parent-to-Child (haplo) Bone Marrow Transplant for Sickle Cell Disease (SCD)

Learn more about this trial

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

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