Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
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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 |
- 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 ]
| Estimated Enrollment: | 25 |
| Study Start Date: | August 2008 |
| Estimated Primary Completion Date: | August 2012 (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).
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.
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Hisham Abdel-Azim, MD | 323-361-8556 | habdelazim@chla.usc.edu |
| United States, California | |
| Children Hospital Los Angeles | Recruiting |
| Los Angeles, California, United States, 90027 | |
| Principal Investigator: | Hisham Abdel-Azim, MD | Childrens Hospital Los Angeles, University of Southern California |
More Information
Additional Information:
No publications provided
| Responsible Party: | Hisham Abdel-Azim, MD, Childrens Hospital Los Angeles, University of Southern California |
| 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 22, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Children's Hospital Los Angeles:
|
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 Sickle cell disease |
Thalassemia 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 |
Additional relevant MeSH terms:
|
Genetic Diseases, Inborn Anemia Anemia, Sickle Cell Chediak-Higashi Syndrome Fucosidosis Granuloma Neutropenia Niemann-Pick Diseases Niemann-Pick Disease, Type A Niemann-Pick Disease, Type C Osteopetrosis Thalassemia Thrombocytopenia Wiskott-Aldrich Syndrome Mucopolysaccharidosis I |
Aphasia, Primary Progressive Pick Disease of the Brain Frontotemporal Dementia Hematologic Diseases Anemia, Hemolytic, Congenital Anemia, Hemolytic Hemoglobinopathies Phagocyte Bactericidal Dysfunction Leukocyte Disorders Immunologic Deficiency Syndromes Immune System Diseases Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases |
ClinicalTrials.gov processed this record on May 21, 2013