Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
Primary Purpose
Non Malignant Disorders, Immunodeficiencies, Congenital Marrow Failures
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Unrelated Umbilical Cord Blood Transplant
Reduced Intensity Conditioning
Sponsored by
About this trial
This is an interventional treatment trial for Non Malignant Disorders focused on measuring Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, SCIDS, Wiskott Aldrich, FEL, HLH, IPEX, LAD, Sickle Cell, Thalassemia, Omenn's Syndrome, Hurler's Syndrome, MLD, ALD, Sanfilippo, Krabbe, Hunter's syndrome, TaySachs, Diamond Blackfan Anemia, transplant, MPS, Gaucher
Eligibility 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
Sites / Locations
- Duke University Medical Center Pediatric Blood and Marrow Transplant Program
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RIC Cord Blood Transplant
Arm Description
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
Outcomes
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.
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
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.
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
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)
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
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
To Describe the Pace of Platelet Recovery
Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00744692
Brief Title
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Malignant Disorders, Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, Sickle Cell, Thalassemia, Lysosomal Storage Disease
Keywords
Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, SCIDS, Wiskott Aldrich, FEL, HLH, IPEX, LAD, Sickle Cell, Thalassemia, Omenn's Syndrome, Hurler's Syndrome, MLD, ALD, Sanfilippo, Krabbe, Hunter's syndrome, TaySachs, Diamond Blackfan Anemia, transplant, MPS, Gaucher
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RIC Cord Blood Transplant
Arm Type
Experimental
Arm Description
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
Intervention Type
Biological
Intervention Name(s)
Unrelated Umbilical Cord Blood Transplant
Intervention Description
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
Intervention Type
Drug
Intervention Name(s)
Reduced Intensity Conditioning
Other Intervention Name(s)
Campath, Hydroxyurea, Fludarabine, Melphalan, Thiotepa
Primary Outcome Measure Information:
Title
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.
Description
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
Secondary Outcome Measure Information:
Title
To Describe the Pace of Neutrophil Recovery
Description
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
Time Frame
42 days post transplant
Title
To Evaluate the Pace of Immune Reconstitution.
Description
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.
Time Frame
1 year post transplant
Title
To Determine the Overall Survival at day180 Post-transplant
Description
To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis
Time Frame
180 days
Title
To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)
Description
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis
Time Frame
100 days post transplant
Title
To Describe the Incidence of Grade 3-4 Organ Toxicity
Time Frame
2 years post transplant
Title
To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure
Time Frame
at least 2 years post transplant
Title
To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant
Time Frame
2 years post transplant
Title
To Describe the Pace of Platelet Recovery
Description
Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions
Time Frame
180 days post transplant
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suhag Parikh, MD
Organizational Affiliation
Duke Pediatric Blood and Marrow Transplant
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center Pediatric Blood and Marrow Transplant Program
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24296492
Citation
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.
Results Reference
derived
Learn more about this trial
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
We'll reach out to this number within 24 hrs