Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
|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 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|
- 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.
- 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
|Study Start Date:||October 2008|
|Study Completion Date:||April 2014|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
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 transplantDrug: Reduced Intensity Conditioning
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00744692
|United States, North Carolina|
|Duke University Medical Center Pediatric Blood and Marrow Transplant Program|
|Durham, North Carolina, United States, 27705|
|Principal Investigator:||Suhag Parikh, MD||Duke Pediatric Blood and Marrow Transplant|