Clinical trial NCT00744692: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-09-01
Enrollment: 22
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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.
timeFrame: 180 days post transplant
Secondary outcomes:
measure: To Describe the Pace of Neutrophil Recovery
timeFrame: 42 days post transplant
measure: To Evaluate the Pace of Immune Reconstitution.
timeFrame: 1 year post transplant
measure: To Determine the Overall Survival at day180 Post-transplant
timeFrame: 180 days
measure: To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)
timeFrame: 100 days post transplant
measure: To Describe the Incidence of Grade 3-4 Organ Toxicity
timeFrame: 2 years post transplant
measure: To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure
timeFrame: at least 2 years post transplant
measure: To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant
timeFrame: 2 years post transplant
measure: To Describe the Pace of Platelet Recovery
timeFrame: 180 days post transplant
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center Pediatric Blood and Marrow Transplant Program
state: North Carolina
Study officials:
affiliation: Duke Pediatric Blood and Marrow Transplant
name: Suhag Parikh, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.