Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00744692
First received: August 28, 2008
Last updated: May 21, 2014
Last verified: May 2014

August 28, 2008
May 21, 2014
October 2008
December 2014   (final data collection date for primary outcome measure)
Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders. [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00744692 on ClinicalTrials.gov Archive Site
  • To describe the pace of neutrophil and platelet recovery [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]
  • To evaluate the pace of immune reconstitution. [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  • To describe the incidence of grade 3-4 organ toxicity [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
  • To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure [ Time Frame: at least 2 years post transplant ] [ Designated as safety issue: No ]
  • To evaluate the incidence of late graft failures at 2 years post-transplant [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

The secondary objectives are:

  • To describe the pace of neutrophil and platelet recovery
  • To evaluate the pace of immune reconstitution.
  • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
  • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
  • To describe the incidence of grade 3-4 organ toxicity
  • To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
  • To evaluate the incidence of late graft failures at 2 years post-transplant
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Non Malignant Disorders
  • Immunodeficiencies
  • Congenital Marrow Failures
  • Hemoglobinopathies
  • Inborn Errors of Metabolism
  • Sickle Cell
  • Thalassemia
  • Lysosomal Storage Disease
  • Biological: Unrelated Umbilical Cord Blood Transplant
    Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
  • Drug: Reduced Intensity Conditioning
    Other Names:
    • Campath
    • Hydroxyurea
    • Fludarabine
    • Melphalan
    • Thiotepa
Experimental: RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
Interventions:
  • Biological: Unrelated Umbilical Cord Blood Transplant
  • Drug: Reduced Intensity Conditioning
Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A, Hale G, Driscoll TA, Martin PL, Page KM, Flickinger K, Moffet J, Niedzwiecki D, Kurtzberg J, Szabolcs P. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
December 2014
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
  • Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
  • Performance score (lansky or karnofsky) greater than or equal to 70
  • Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
  • Informed consent
  • Not pregnant or breast feeding
  • Minimum life expectancy of at least 6 months
  • HIV negative
  • No uncontrolled infections at the time of cytoreduction
  • Disease specific inclusion criteria

Exclusion Criteria:

  • Patients with hemoglobinopathies > 3 years of age
  • UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
  • Available HLA-matched related living donor able to donate without previous UCB donation
  • Allogeneic hematopoietic stem cell transplant within the previous 6 months
  • Any active malignancy, MDS, or any history of malignancy
  • Severe acquired aplastic anemia
  • DLCO < 60% of normal value for age; requirement for supplemental oxygen
  • Uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms)
  • Pregnancy or nursing mother
  • HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR
  • Any condition that precludes serial follow-up
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00744692
Pro00008753
No
Duke University
Duke University
Not Provided
Principal Investigator: Suhag Parikh, MD Duke Pediatric Blood and Marrow Transplant
Duke University
May 2014

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