Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells - Full Text View

Sponsor:	Children's Hospital Los Angeles
Information provided by:	Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:	NCT00730314

Purpose

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 Thalassemia Anemia Granuloma Wiskott-Aldrich Syndrome Chediak Higashi Syndrome Osteopetrosis Neutropenia Thrombocytopenia Hurler Disease Niemann-Pick Disease Fucosidosis	Procedure: Hematopoietic stem cell transplantation	Phase I Phase II

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:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome Chediak-Higashi syndrome CHMP2B-related frontotemporal dementia cholesteryl ester storage disease complement factor I deficiency cyclic neutropenia Diamond-Blackfan anemia dyserythropoietic anemia and thrombocytopenia Farber lipogranulomatosis frontotemporal dementia with parkinsonism-17 fucosidosis GRN-related frontotemporal dementia hemophilia inclusion body myopathy with early-onset Paget disease and frontotemporal dementia Melnick-Needles syndrome mucopolysaccharidosis type I mucopolysaccharidosis type IV MYH9-related disorder Niemann-Pick disease osteopetrosis Schindler disease severe congenital neutropenia sickle cell disease succinic semialdehyde dehydrogenase deficiency Wiskott-Aldrich syndrome X-linked hyper IgM syndrome X-linked lymphoproliferative disease Help Me Understand Genetics

MedlinePlus related topics: Anemia Bone Marrow Transplantation Sickle Cell Anemia Thalassemia

U.S. FDA Resources

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

Primary Outcome Measures:

toxicities [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
engraftment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
immune reconstitution [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
overall and event free survival survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	25
Study Start Date:	August 2008
Estimated Primary Completion Date:	August 2012 (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).

We hypothesize 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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00730314

Contacts

Contact: Hisham Abdel-Azim, MD

323-361-8556

habdelazim@chla.usc.edu

Locations

United States, California
Children Hospital Los Angeles	Recruiting
Los Angeles, California, United States, 90027

Sponsors and Collaborators

Children's Hospital Los Angeles

Investigators

Principal Investigator:

Hisham Abdel-Azim, MD

Childrens Hospital Los Angeles, University of Southern California

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Hisham Abdel-Azim, MD, Childrens Hospital Los Angeles, University of Southern California
ClinicalTrials.gov Identifier:	NCT00730314 History of Changes
Other Study ID Numbers:	CCI #07-00119, CHLA-#07-00119
Study First Received:	August 6, 2008
Last Updated:	June 22, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Children's Hospital Los Angeles:

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
Sickle cell disease

Thalassemia
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

Additional relevant MeSH terms:

Anemia
Anemia, Sickle Cell
Chediak-Higashi Syndrome
Fucosidosis
Granuloma
Genetic Diseases, Inborn
Neutropenia
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Osteopetrosis
Thalassemia
Thrombocytopenia
Wiskott-Aldrich Syndrome
Mucopolysaccharidosis I

Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Dementia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Immunologic Deficiency Syndromes
Immune System Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases

ClinicalTrials.gov processed this record on February 09, 2012