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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00744692
First received: August 28, 2008
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Non Malignant Disorders
Immunodeficiencies
Congenital Marrow Failures
Hemoglobinopathies
Inborn Errors of Metabolism
Sickle Cell
Thalassemia
Lysosomal Storage Disease
Biological: Unrelated Umbilical Cord Blood Transplant
Drug: Reduced Intensity Conditioning
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • To Describe the Pace of Neutrophil Recovery [ Time Frame: 42 days post transplant ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ 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 ]
  • To Describe the Pace of Platelet Recovery [ Time Frame: 180 days post transplant ] [ Designated as safety issue: No ]
    Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions


Enrollment: 22
Study Start Date: October 2008
Study Completion Date: April 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
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

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
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00744692

Locations
United States, North Carolina
Duke University Medical Center Pediatric Blood and Marrow Transplant Program
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Suhag Parikh, MD Duke Pediatric Blood and Marrow Transplant
  More Information

No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00744692     History of Changes
Other Study ID Numbers: Pro00008753
Study First Received: August 28, 2008
Results First Received: July 23, 2014
Last Updated: July 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Omenn's Syndrome
Immunodeficiencies
Congenital Marrow Failures
Hemoglobinopathies
Inborn Errors of Metabolism
SCIDS
Wiskott Aldrich
FEL
HLH
IPEX
LAD
Sickle Cell
Thalassemia
Hurler's Syndrome
MLD
ALD
Sanfilippo
Krabbe
Hunter's syndrome
TaySachs
Diamond Blackfan Anemia
transplant
MPS
Gaucher

Additional relevant MeSH terms:
Disease
Hemoglobinopathies
Immunologic Deficiency Syndromes
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Thalassemia
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 29, 2014