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

Thalassemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00744692
• Other study ID #: Pro00008753
• Status: Completed
• Phase: Phase 1
• First received: August 28, 2008
• Last updated: July 23, 2014
• Start date: October 2008
• Est. completion date: April 2014

Study information

• Verified date: July 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Marrow Failures
• Hemoglobinopathies
• Immunodeficiencies
• Immunologic Deficiency Syndromes
• Inborn Errors of Metabolism
• Lysosomal Storage Disease
• Lysosomal Storage Diseases
• Metabolism, Inborn Errors
• Non Malignant Disorders
• Sickle Cell
• Thalassemia

Intervention

Biological:
• Unrelated Umbilical Cord Blood Transplant
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant

Drug:
• Reduced Intensity Conditioning

Locations

Country	Name	City	State
United States	Duke University Medical Center Pediatric Blood and Marrow Transplant Program	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	180 days post transplant	No
Secondary	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	42 days post transplant	No
Secondary	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.	1 year post transplant	No
Secondary	To Determine the Overall Survival at day180 Post-transplant	To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis	180 days	No
Secondary	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	100 days post transplant	No
Secondary	To Describe the Incidence of Grade 3-4 Organ Toxicity		2 years post transplant	No
Secondary	To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure		at least 2 years post transplant	No
Secondary	To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant		2 years post transplant	No
Secondary	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	180 days post transplant	No