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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00744692
Recruitment Status : Completed
First Posted : September 1, 2008
Results First Posted : August 13, 2014
Last Update Posted : August 13, 2014
Sponsor:
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE August 28, 2008
First Posted Date  ICMJE September 1, 2008
Results First Submitted Date  ICMJE July 23, 2014
Results First Posted Date  ICMJE August 13, 2014
Last Update Posted Date August 13, 2014
Study Start Date  ICMJE October 2008
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2014)		 Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders. [ Time Frame: 180 days post transplant ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 29, 2008)		 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2014)
  • To Describe the Pace of Neutrophil Recovery [ Time Frame: 42 days post transplant ]
    Neutrophil recovery was defined as the first day of an absolute neutrophil count (ANC) more than 500/uL for 3 consecutive days not secondary to granulocyte infusions
  • To Evaluate the Pace of Immune Reconstitution. [ Time Frame: 1 year post transplant ]
    Immune reconstitution after RIC in UCBT was described. CD4 count is a standard measure of immune reconstitution and is described here. Additional data is available upon request.
  • To Determine the Overall Survival at day180 Post-transplant [ Time Frame: 180 days ]
    To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis
  • To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV) [ Time Frame: 100 days post transplant ]
    To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis
  • To Describe the Incidence of Grade 3-4 Organ Toxicity [ Time Frame: 2 years post transplant ]
  • To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure [ Time Frame: at least 2 years post transplant ]
  • To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant [ Time Frame: 2 years post transplant ]
  • To Describe the Pace of Platelet Recovery [ Time Frame: 180 days post transplant ]
    Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2008)
  • To describe the pace of neutrophil and platelet recovery [ Time Frame: 180 days post transplant ]
  • To evaluate the pace of immune reconstitution. [ Time Frame: 2 years post transplant ]
  • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant [ Time Frame: 180 days ]
  • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD [ Time Frame: 2 years post transplant ]
  • To describe the incidence of grade 3-4 organ toxicity [ Time Frame: 2 years post transplant ]
  • To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure [ Time Frame: at least 2 years post transplant ]
  • To evaluate the incidence of late graft failures at 2 years post-transplant [ Time Frame: 2 years post transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
Official Title  ICMJE A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation
Brief Summary 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.
Detailed Description

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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Malignant Disorders
  • Immunodeficiencies
  • Congenital Marrow Failures
  • Hemoglobinopathies
  • Inborn Errors of Metabolism
  • Sickle Cell
  • Thalassemia
  • Lysosomal Storage Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
Interventions:
  • Biological: Unrelated Umbilical Cord Blood Transplant
  • Drug: Reduced Intensity Conditioning
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 23, 2014)		 22
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2008)		 20
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00744692
Other Study ID Numbers  ICMJE Pro00008753
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Duke University
Original Responsible Party Dr. Suhag Parikh and Dr. Paul Szabolcs, Duke University Medical Center Institutional Review Board
Current Study Sponsor  ICMJE Duke University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Suhag Parikh, MD Duke Pediatric Blood and Marrow Transplant
PRS Account Duke University
Verification Date July 2014

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