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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
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

First Posted
August 28, 2008
Last Updated
July 23, 2014
Sponsor
Duke University
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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

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

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