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

• ClinicalTrials.gov Identifier: NCT00730314
• Recruitment Status: Completed
• First Posted: August 8, 2008
• Last Update Posted: June 23, 2016
• Sponsor: Children's Hospital Los Angeles
• Information provided by (Responsible Party): Hisham Abdel-Azim, Children's Hospital Los Angeles

Tracking Information

• First Submitted Date: August 6, 2008
• First Posted Date: August 8, 2008
• Last Update Posted Date: June 23, 2016
• Study Start Date: August 2008
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2010)

• toxicities [ Time Frame: 3 years ]
• adverse events [ Time Frame: 3 years ]
• engraftment [ Time Frame: 1 year ]
• immune reconstitution [ Time Frame: 3 years ]
• overall and event free survival survival [ Time Frame: 3 years ]

• Original Primary Outcome Measures (submitted: August 7, 2008): toxicities, adverse events, engraftment,immune reconstitution,overall and event free survival survival. [ Time Frame: 1 year ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
• 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

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.

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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sickle Cell Disease
• Thalassemia
• Anemia
• Granuloma
• Wiskott-Aldrich Syndrome
• Chediak Higashi Syndrome
• Osteopetrosis
• Neutropenia
• Thrombocytopenia
• Hurler Disease
• Niemann-Pick Disease
• Fucosidosis

Intervention

Procedure: Hematopoietic stem cell transplantation

hematopoietic stem cell transplantation conditioning regimen depending on graft source

Study Arms

• Experimental: 1
  Unrelated donor
  Intervention: Procedure: Hematopoietic stem cell transplantation
• Experimental: 2
  Cord Blood
  Intervention: Procedure: Hematopoietic stem cell transplantation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 7, 2008): 25
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00730314
• Other Study ID Numbers: CCI #07-00119; CHLA-#07-00119
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hisham Abdel-Azim, Children's Hospital Los Angeles
• Original Responsible Party: Hisham Abdel-Azim, MD, Childrens Hospital Los Angeles, University of Southern California
• Current Study Sponsor: Children's Hospital Los Angeles
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Hisham Abdel-Azim, MD; Childrens Hospital Los Angeles, University of Southern California

• PRS Account: Children's Hospital Los Angeles
• Verification Date: June 2016