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

Phase 1

Completed

• Conditions: Immunodeficiencies; Congenital Marrow Failures; Inborn Errors of Metabolism; Non Malignant Disorders; Hemoglobinopathies; Sickle Cell; Thalassemia; Lysosomal Storage Disease
• Interventions: Biological: Unrelated Umbilical Cord Blood Transplant; Drug: Reduced Intensity Conditioning

• Registration Number: NCT00744692
• Lead Sponsor: Duke University

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2008-08-28
• Study First Submitted QC: 2008-08-29
• Study First Posted: 2008-09-01
• Study Start: 2008-10
• Primary Completion: 2012-12
• Study Completion: 2014-04
• Status Verified: 2014-07
• Results First Submitted: 2014-07-23
• Results First Submitted QC: 2014-07-23
• Last Update Submitted: 2014-07-23
• Results First Posted: 2014-08-13
• Last Update Posted: 2014-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RIC Cord Blood Transplant	Unrelated Umbilical Cord Blood Transplant	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
RIC Cord Blood Transplant	Reduced Intensity Conditioning	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant

Primary Outcome Measures

Name	Time	Method
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.	180 days post transplant	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

Name	Time	Method
To Describe the Pace of Neutrophil Recovery	42 days post transplant	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.	1 year post transplant	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	180 days	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)	100 days post transplant	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	2 years post transplant
To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure	at least 2 years post transplant
To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant	2 years post transplant
To Describe the Pace of Platelet Recovery	180 days post transplant	Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions

Trial Locations

Locations (1)

Duke University Medical Center Pediatric Blood and Marrow Transplant Program; 🇺🇸 Durham, North Carolina, United States