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NCT Number: NCT00730314

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

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.

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Key information

Conditions

Sickle Cell Disease Agranulocytosis Albinism Anemia Anemia, Dyserythropoietic, Congenital Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Platelet Disorders Blood Protein Disorders Bone Diseases Bone Diseases, Developmental Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Chediak Higashi Syndrome Chediak-Higashi Syndrome Chronic Disease Congenital amegakaryocytic thrombocytopenia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Cytopenia Disease Attributes Dysgammaglobulinemia Eye Diseases Eye Diseases, Hereditary Fucosidosis Genetic Diseases, Inborn Genetic Diseases, X-Linked Granuloma Granulomatous Disease, Chronic Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Hemorrhagic Disorders Histiocytosis Histiocytosis, Non-Langerhans-Cell Hurler Disease Hyper-IgM Immunodeficiency Syndrome Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Leukocyte Disorders Leukopenia Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lymphatic Diseases Lymphopenia Lymphoproliferative Disorders Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis I Musculoskeletal Diseases Nervous System Diseases Neutropenia Neutropenia, Severe Congenital, Autosomal Recessive 3 Niemann-Pick Disease Niemann-Pick Diseases Nutritional and Metabolic Diseases Osteochondrodysplasias Osteopetrosis Osteosclerosis Pathologic Processes Pathological Conditions, Signs and Symptoms Phagocyte Bactericidal Dysfunction Primary Immunodeficiency Diseases Skin and Connective Tissue Diseases Sphingolipidoses Thalassemia Thrombocytopenia Wiskott-Aldrich Syndrome

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Children Hospital Los Angeles

Los Angeles, California, 90027, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Hematopoietic Stem Cell Transplantation

Procedure

hematopoietic stem cell transplantation conditioning regimen depending on graft source

Primary outcomes

  1. toxicities

    Time frame: 3 years

  2. adverse events

    Time frame: 3 years

  3. engraftment

    Time frame: 1 year

  4. immune reconstitution

    Time frame: 3 years

  5. overall and event free survival survival

    Time frame: 3 years

Sponsors and collaborators

Lead sponsor

Children's Hospital Los Angeles

Other

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2015
Study completion
2015
First posted
Aug 8, 2008
Registry last updated
Jun 23, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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