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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Children's Hospital Los Angeles.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00730314
First received: August 6, 2008
Last updated: June 22, 2011
Last verified: June 2011

August 6, 2008
June 22, 2011
August 2008
August 2012   (final data collection date for primary outcome measure)
  • 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 ]
toxicities, adverse events, engraftment,immune reconstitution,overall and event free survival survival. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00730314 on ClinicalTrials.gov Archive Site
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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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
hematopoietic stem cell transplantation conditioning regimen depending on graft source
  • Experimental: 1
    Unrelated donor
    Intervention: Procedure: Hematopoietic stem cell transplantation
  • Experimental: 2
    Cord Blood
    Intervention: Procedure: Hematopoietic stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
25
Not Provided
August 2012   (final data collection date for primary outcome measure)

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).
Both
up to 21 Years
No
Contact: Hisham Abdel-Azim, MD 323-361-8556 habdelazim@chla.usc.edu
United States
 
NCT00730314
CCI #07-00119, CHLA-#07-00119
Yes
Hisham Abdel-Azim, MD, Childrens Hospital Los Angeles, University of Southern California
Children's Hospital Los Angeles
Not Provided
Principal Investigator: Hisham Abdel-Azim, MD Childrens Hospital Los Angeles, University of Southern California
Children's Hospital Los Angeles
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP