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

NCT00730314 | Completed Phase 1 DMC

• 2 other identifiers: CCI #07-00119CHLA-#07-00119
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• toxicities

  3 years

• adverse events

  3 years

• engraftment

  1 year

• immune reconstitution

  3 years

• overall and event free survival survival

  3 years

Study Arms (2)

1

EXPERIMENTAL

Unrelated donor

Procedure: Hematopoietic stem cell transplantation

2

EXPERIMENTAL

Cord Blood

Procedure: Hematopoietic stem cell transplantation

Interventions

Hematopoietic stem cell transplantation PROCEDURE

hematopoietic stem cell transplantation conditioning regimen depending on graft source

1; 2

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (1)

Children Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Anemia; Granuloma; Wiskott-Aldrich Syndrome; Chediak-Higashi Syndrome; Osteopetrosis; Neutropenia; Thrombocytopenia; Mucopolysaccharidosis I; Niemann-Pick Diseases; Fucosidosis; Anemia, Dyserythropoietic, Congenital; Genetic Diseases, Inborn; Granulomatous Disease, Chronic; Hyper-IgM Immunodeficiency Syndrome; Neutropenia, Severe Congenital, Autosomal Recessive 3; Lymphoproliferative Disorders; Congenital amegakaryocytic thrombocytopenia

Interventions

Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Albinism; Eye Diseases, Hereditary; Eye Diseases; Phagocyte Bactericidal Dysfunction; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Agranulocytosis; Blood Platelet Disorders; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Chronic Disease; Disease Attributes; Dysgammaglobulinemia; Blood Protein Disorders; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Hisham Abdel-Azim, MD

  Childrens Hospital Los Angeles, University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 8, 2008
• Study Start: August 1, 2008
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: June 23, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)