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

Sponsored by:	Duke University
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00744692

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	Other: Unrelated Umbilical Cord Blood Transplant	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment
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:

Genetics Home Reference related topics: mucopolysaccharidosis type II

U.S. FDA Resources

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 reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders. [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To describe the pace of neutrophil and platelet recovery [ Time Frame: 180 days post transplant ] [ Designated as safety issue: Yes ]
To evaluate the pace of immune reconstitution. [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant [ Time Frame: 180 days ] [ Designated as safety issue: No ]
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
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 ]

Estimated Enrollment:	20
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Reduced Intensity Conditioning for unrelated umbilical cord blood transplant

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

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

Contacts

Contact: Jennifer H Baker, RN	919-668-6536	baker133@mc.duke.edu
Contact: Suhag Parikh, MD	919-668-1121	suhag.parikh@duke.edu

Locations

United States, North Carolina
Duke University Medical Center Pediatric Blood and Marrow Transplant Program	Recruiting
Durham, North Carolina, United States, 27705
Principal Investigator: Suhag Parikh, MD
Principal Investigator: Paul Szabolcs, MD

Sponsors and Collaborators

Duke University

Investigators

Principal Investigator:	Suhag Parikh, MD	Duke Pediatric Blood and Marrow Transplant
Principal Investigator:	Paul Szabolcs, MD	Duke Pediatric Blood and Marrow Transplant

More Information

No publications provided

Responsible Party:	Duke University Medical Center Institutional Review Board ( Dr. Suhag Parikh and Dr. Paul Szabolcs )
Study ID Numbers:	Pro00008753
Study First Received:	August 28, 2008
Last Updated:	March 15, 2009
ClinicalTrials.gov Identifier:	NCT00744692 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

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

Study placed in the following topic categories:

Mucopolysaccharidosis II
Diamond-Blackfan Anemia
Metabolic Diseases
Hematologic Diseases
Anemia
Mucopolysaccharidosis Type II
Thalassemia
Immunologic Deficiency Syndromes
Metabolism, Inborn Errors

Aase Syndrome
Genetic Diseases, Inborn
Hemoglobinopathies
Anemia, Diamond-Blackfan
Omenn Syndrome
Hemoglobinopathy
Metabolic Disorder
Hunter-McAlpine Syndrome

Additional relevant MeSH terms:

Metabolism, Inborn Errors
Metabolic Diseases
Pathologic Processes
Disease
Immune System Diseases

Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on September 10, 2009