- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00730314
Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90027
- Children Hospital Los Angeles
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 1
Unrelated donor
|
hematopoietic stem cell transplantation conditioning regimen depending on graft source
|
EXPERIMENTAL: 2
Cord Blood
|
hematopoietic stem cell transplantation conditioning regimen depending on graft source
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
engraftment
Time Frame: 1 year
|
1 year
|
toxicities
Time Frame: 3 years
|
3 years
|
adverse events
Time Frame: 3 years
|
3 years
|
immune reconstitution
Time Frame: 3 years
|
3 years
|
overall and event free survival survival
Time Frame: 3 years
|
3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hisham Abdel-Azim, MD, Childrens Hospital Los Angeles, University of Southern California
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- CGD
- sickle cell disease
- BMT
- HSCT
- bone marrow transplantation
- Genetic diseases
- leukodystrophies
- thalassemia
- Osteopetrosis
- LAD I
- unrelated
- HLH
- Wiskott-Aldrich syndrome
- Hurler
- chronic granulomatous disease
- leukodystrophy
- Niemann-Pick disease
- Fucosidosis
- Blackfan-Diamond anemia
- Red blood cell defects
- Leukocyte defects and immune deficiencies
- Hereditary Lymphohistiocytosis
- 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
- Stem cell defects
- reticular agenesis
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Eye Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Disease
- Hematologic Diseases
- Blood Coagulation Disorders, Inherited
- Hemorrhagic Disorders
- Genetic Diseases, X-Linked
- Musculoskeletal Diseases
- Connective Tissue Diseases
- Neurodegenerative Diseases
- Anemia
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Eye Diseases, Hereditary
- Bone Diseases
- Blood Coagulation Disorders
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Mucinoses
- Lipid Metabolism Disorders
- Dementia
- Blood Platelet Disorders
- Agranulocytosis
- Leukopenia
- Leukocyte Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Hemoglobinopathies
- Language Disorders
- Communication Disorders
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Bone Diseases, Developmental
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Phagocyte Bactericidal Dysfunction
- Aphasia
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Osteochondrodysplasias
- Primary Immunodeficiency Diseases
- Lymphopenia
- Mucopolysaccharidoses
- Osteosclerosis
- Albinism
- Syndrome
- Mucopolysaccharidosis I
- Neutropenia
- Anemia, Sickle Cell
- Thrombocytopenia
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Granuloma
- Thalassemia
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
- Genetic Diseases, Inborn
- Wiskott-Aldrich Syndrome
- Osteopetrosis
- Chediak-Higashi Syndrome
- Fucosidosis
Other Study ID Numbers
- CCI #07-00119
- CHLA-#07-00119
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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