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

This study has been completed.
Information provided by (Responsible Party):
Hisham Abdel-Azim, Children's Hospital Los Angeles Identifier:
First received: August 6, 2008
Last updated: June 21, 2016
Last verified: June 2016

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.

Condition Intervention Phase
Sickle Cell Disease
Wiskott-Aldrich Syndrome
Chediak Higashi Syndrome
Hurler Disease
Niemann-Pick Disease
Procedure: Hematopoietic stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • toxicities [ Time Frame: 3 years ]
  • adverse events [ Time Frame: 3 years ]
  • engraftment [ Time Frame: 1 year ]
  • immune reconstitution [ Time Frame: 3 years ]
  • overall and event free survival survival [ Time Frame: 3 years ]

Enrollment: 25
Study Start Date: August 2008
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Unrelated donor
Procedure: Hematopoietic stem cell transplantation
hematopoietic stem cell transplantation conditioning regimen depending on graft source
Experimental: 2
Cord Blood
Procedure: Hematopoietic stem cell transplantation
hematopoietic stem cell transplantation conditioning regimen depending on graft source

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.


Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).
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Please refer to this study by its identifier: NCT00730314

United States, California
Children Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Principal Investigator: Hisham Abdel-Azim, MD Childrens Hospital Los Angeles, University of Southern California
  More Information

Additional Information:
Responsible Party: Hisham Abdel-Azim, Principle Investigator, Children's Hospital Los Angeles Identifier: NCT00730314     History of Changes
Other Study ID Numbers: CCI #07-00119
Study First Received: August 6, 2008
Last Updated: June 21, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Children's Hospital Los Angeles:
Niemann-Pick disease
bone marrow transplantation
sickle cell disease
Blackfan-Diamond anemia
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
congenital neutropenia
X-linked lymphoproliferative disease
Platelets defects
Congenital amegakaryocytic thrombocytopenia
Metabolic and storage disorders
Hurler disease

Additional relevant MeSH terms:
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Anemia, Sickle Cell
Wiskott-Aldrich Syndrome
Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Chediak-Higashi Syndrome
Mucopolysaccharidosis I
Pathologic Processes
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Blood Platelet Disorders
Leukocyte Disorders
Lymphoproliferative Disorders processed this record on April 25, 2017