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

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 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:

Genetics Home Reference related topics: CHMP2B-related frontotemporal dementia Chediak-Higashi syndrome GRN-related frontotemporal dementia Niemann-Pick disease Wiskott-Aldrich syndrome cyclic neutropenia dyserythropoietic anemia and thrombocytopenia frontotemporal dementia with parkinsonism-17 fucosidosis osteopetrosis

Genetic and Rare Diseases Information Center resources: Sickle Cell Anemia Thalassemia Pick's Disease Frontotemporal Dementia Frontotemporal Dementia, Ubiquitin-positive Primary Progressive Aphasia Semantic Dementia Niemann-Pick Disease Type A Wiskott Aldrich Syndrome Granulocytopenia Chronic Granulomatous Disease Hurler Syndrome Diamond-Blackfan Anemia Leukodystrophy Osteopetrosis X-linked Lymphoproliferative Syndrome Fucosidosis Chediak-Higashi Syndrome Congenital Amegakaryocytic Thrombocytopenia Niemann-Pick Disease Type C1 Mucopolysaccharidosis Mucopolysaccharidosis Type I Sphingolipidosis Mucopolysaccharidosis Type IV

U.S. FDA Resources

Further study details as provided by Hisham Abdel-Azim, 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.

Eligibility


Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


United States, California
Children Hospital Los Angeles
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


Responsible Party:	Hisham Abdel-Azim, Principle Investigator, Children's Hospital Los Angeles
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 21, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Hisham Abdel-Azim, Children's Hospital Los Angeles:


Fucosidosis 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

Fucosidosis
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

Additional relevant MeSH terms:


Fucosidosis Syndrome Anemia, Sickle Cell Thrombocytopenia Neutropenia Thalassemia Granuloma Pick Disease of the Brain Aphasia, Primary Progressive Frontotemporal Dementia Wiskott-Aldrich Syndrome Niemann-Pick Diseases Niemann-Pick Disease, Type A Niemann-Pick Disease, Type C Osteopetrosis	Chediak-Higashi Syndrome Mucopolysaccharidosis I Disease Pathologic Processes Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Blood Platelet Disorders Agranulocytosis Leukopenia Leukocyte Disorders Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on July 13, 2017