Overview

This trial is active, not recruiting.

Conditions non malignant disorders, immunodeficiencies, congenital marrow failures, hemoglobinopathies, inborn errors of metabolism, sickle cell, thalassemia, lysosomal storage disease
Treatments unrelated umbilical cord blood transplant, reduced intensity conditioning
Phase phase 1
Sponsor Duke University
Start date October 2008
End date December 2014
Trial size 20 participants
Trial identifier NCT00744692, Pro00008753

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
unrelated umbilical cord blood transplant
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
reduced intensity conditioning Campath

Primary Outcomes

Measure
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 Outcomes

Measure
To describe the pace of neutrophil and platelet recovery
time frame: 180 days post transplant
To evaluate the pace of immune reconstitution.
time frame: 2 years post transplant
To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
time frame: 180 days
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
time frame: 2 years post transplant
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

Eligibility Criteria

Male or female participants up to 21 years old.

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

Additional Information

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
Principal investigator Suhag Parikh, MD
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
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Duke University.