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Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells

Primary Purpose

Sickle Cell Disease, Thalassemia, Anemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hematopoietic stem cell transplantation
Sponsored by
Children's Hospital Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring unrelated, BMT, HSCT, bone marrow transplantation, sickle cell disease, thalassemia, CGD, HLH, Blackfan-Diamond anemia, Hurler, leukodystrophy, LAD I, Genetic diseases, Red blood cell defects, Leukocyte defects and immune deficiencies, Hereditary Lymphohistiocytosis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Chediak Higashi syndrome, CD40 ligand deficiency, Hyper IgM syndrome, leucocytes adhesion defect type 1, Osteopetrosis, congenital neutropenia, X-linked lymphoproliferative disease, Platelets defects, Congenital amegakaryocytic thrombocytopenia, Metabolic and storage disorders, Hurler disease, leukodystrophies, Niemann-Pick disease, Fucosidosis, Stem cell defects, reticular agenesis

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible sibling or other family donor
  • Genetic diseases that would be candidates for this protocol includes those that have been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders and Stem cell defects.
  • Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and not requiring dialysis.
  • Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable to perform pulmonary function tests, then O2 saturation ≥ 92% in room air.
  • Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction ≥ 26%
  • Hepatic: Bilirubin ≤3x upper limit of normal (ULN) and ALT and AST ≤ 5x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome).
  • Patients will be 0-21 years of age.
  • Disease specific inclusion criteria (as applicable per protocol).

Exclusion Criteria:

  • Recipients should not have any of the general exclusion criteria, and disease specific exclusion criteria when applicable.
  • Patient with histocompatible sibling
  • End-organ failure that precludes the ability to tolerate the transplant procedure, including the conditioning regimen.
  • Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis.
  • Congenital heart disease resulting in congestive heart failure.
  • Severe residual CNS disease/impairment [(other than hemiplegia alone) e.g. coma or intractable seizures]
  • Ventilatory failure
  • Major congenital anomalies that adversely affect survival, e.g. CNS malformations
  • Lansky score < 40% or Karnofsky score < 60%
  • HIV seropositivity
  • Diagnosis of Fanconi's anemia, Severe Combined Immunodeficiency (SCID)
  • Positive pregnancy test (For female patients in child bearing period)
  • Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress)
  • Disease specific exclusion criteria (as applicable per protocol).

Sites / Locations

  • Children Hospital Los Angeles

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Unrelated donor

Cord Blood

Outcomes

Primary Outcome Measures

toxicities
adverse events
engraftment
immune reconstitution
overall and event free survival survival

Secondary Outcome Measures

Full Information

First Posted
August 6, 2008
Last Updated
June 21, 2016
Sponsor
Children's Hospital Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT00730314
Brief Title
Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
Official Title
Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital Los Angeles

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic diseases of blood cell include: Red blood cell defects e.g. hemoglobinopathies (sickle cell disease and thalassemia), Blackfan-Diamond anemia and congenital or chronic hemolytic anemias; White blood cells defects/immune deficiencies e.g. chronic granulomatous disease, Wiskott-Aldrich syndrome,Osteopetrosis, Kostmann's syndrome (congenital neutropenia), Hereditary Lymphohistiocytosis (HLH); Platelets defects e.g.Congenital amegakaryocytic thrombocytopenia; Metabolic/storage disorders e.g. leukodystrophies,mucopolysaccharidoses as Hurler disease;Stem cell defects e.g.reticular agenesis, among many other rare similar conditions. The study treatment plan uses a new transplant treatment regimen that aims to try to decrease the acute toxicities and complications associated with the standard treatment plans and to improve outcome The blood stem cells will be derived from either unrelated donor or unrelated umbilical cord blood.
Detailed Description
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD) or 2) unrelated umbilical cord blood (UCB). Patients will receive a novel conditioning regimen with Busulfan, Cytoxan and Fludarabine (Bu/Cy/Flu) and either Alemtuzumab (Campath 1H) for recipients of a MUD or rabbit Antithymocyte Globulin (rATG) for recipients of unrelated UCB prior to hematopoietic stem cell transplant (HSCT). It is hypothesized that reduced dosages of Cytoxan will decrease the acute toxicities associated with the standard chemotherapies of Busulfan and Cytoxan (i.e. sinusoidal obstructive syndrome (SOS), hemorrhagic cystitis and mucositis). And the addition of fludarabine to a conditioning regimen with myeloablative doses of Busulfan and reduced dosages of Cytoxan prior to HSCT will overcome the engraftment barrier posed by an intact immune system, which is seen in patients with a genetic disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Thalassemia, Anemia, Granuloma, Wiskott-Aldrich Syndrome, Chediak Higashi Syndrome, Osteopetrosis, Neutropenia, Thrombocytopenia, Hurler Disease, Niemann-Pick Disease, Fucosidosis
Keywords
unrelated, BMT, HSCT, bone marrow transplantation, sickle cell disease, thalassemia, CGD, HLH, Blackfan-Diamond anemia, Hurler, leukodystrophy, LAD I, Genetic diseases, Red blood cell defects, Leukocyte defects and immune deficiencies, Hereditary Lymphohistiocytosis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Chediak Higashi syndrome, CD40 ligand deficiency, Hyper IgM syndrome, leucocytes adhesion defect type 1, Osteopetrosis, congenital neutropenia, X-linked lymphoproliferative disease, Platelets defects, Congenital amegakaryocytic thrombocytopenia, Metabolic and storage disorders, Hurler disease, leukodystrophies, Niemann-Pick disease, Fucosidosis, Stem cell defects, reticular agenesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Unrelated donor
Arm Title
2
Arm Type
Experimental
Arm Description
Cord Blood
Intervention Type
Procedure
Intervention Name(s)
Hematopoietic stem cell transplantation
Intervention Description
hematopoietic stem cell transplantation conditioning regimen depending on graft source
Primary Outcome Measure Information:
Title
toxicities
Time Frame
3 years
Title
adverse events
Time Frame
3 years
Title
engraftment
Time Frame
1 year
Title
immune reconstitution
Time Frame
3 years
Title
overall and event free survival survival
Time Frame
3 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible sibling or other family donor Genetic diseases that would be candidates for this protocol includes those that have been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders and Stem cell defects. Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and not requiring dialysis. Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable to perform pulmonary function tests, then O2 saturation ≥ 92% in room air. Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction ≥ 26% Hepatic: Bilirubin ≤3x upper limit of normal (ULN) and ALT and AST ≤ 5x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome). Patients will be 0-21 years of age. Disease specific inclusion criteria (as applicable per protocol). Exclusion Criteria: Recipients should not have any of the general exclusion criteria, and disease specific exclusion criteria when applicable. Patient with histocompatible sibling End-organ failure that precludes the ability to tolerate the transplant procedure, including the conditioning regimen. Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis. Congenital heart disease resulting in congestive heart failure. Severe residual CNS disease/impairment [(other than hemiplegia alone) e.g. coma or intractable seizures] Ventilatory failure Major congenital anomalies that adversely affect survival, e.g. CNS malformations Lansky score < 40% or Karnofsky score < 60% HIV seropositivity Diagnosis of Fanconi's anemia, Severe Combined Immunodeficiency (SCID) Positive pregnancy test (For female patients in child bearing period) Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress) Disease specific exclusion criteria (as applicable per protocol).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hisham Abdel-Azim, MD
Organizational Affiliation
Childrens Hospital Los Angeles, University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.childrenshospitalla.org
Description
Related Info

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Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells

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