A New Approach to Improve Long-term Hematopoietic Recovery After Allogeneic Umbilical Cord Blood Transplantation in Children - Intrabone Infusion of Umbilical Cord Blood Stem Cells
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Platelet recovery rate
Study Overview
Brief Summary
The purpose of this study is to determine if the method of intrabone infusion of hematologic stem cells can increase and accelerate hematopoietic reconstitution after umbilical cord blood transplantation in pediatric patients.
Detailed Description
Umbilical cord blood transplantation (UCBT) has been increasingly used to treat malignant and non-malignant haematological, immunodeficiency and some metabolic diseases. UCBT offers the advantages of easy procurement, no risk to donors, a reduced risk of transmitting infections, immediate availability of cryopreserved units, and acceptable partial HLA mismatches. However, patients treated with UCBT show delayed hematopoietic and immunological recoveries, have higher rates of infection, and relapse from the original malignant disease, which can all lead to life threatening problems. UCBT can also result in a higher rate of graft failure compared to other hematopoietic stem cell transplantation (HSCT) sources. The problem of a slower hematopoietic recovery post-UCBT has been addressed using a number of different approaches in adult patients.In adults, use of intrabone injection of cord blood results in a faster hematopoietic recovery in a phase II study. However, there is no clinical trial in pediatric patients.
This study is addressed to determine if a change in the cord blood stem cell infusion method can increase and accelerate hematopoietic reconstitution after UCBT in pediatric patients.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •One to 21 years of age;
- •More than 10 kg in weight;
- •Diagnosis of hematopoietic disorders (malignant or not) with an indication for hematopoietic stem cell transplantation;
- •Absence of an HLA-identical related donor;
- •Availability of a single cord blood (CB) with at least 3 x 10^7 nucleated cells (NCs)/kg (if HLA identical or 1 HLA-mismatch) or at least 4 x 10^7 NCs/kg (if a 2 HLA-mismatch) at freezing. Use of two CB units ("double cord transplant") will be allowed provided that: 1) a single CB unit fulfilling the above criteria is not available; 2) a maximum of 2 HLA mismatch is present for each CB unit; and 3) a minimum of 4 x 10^7 NCs/kg (as the sum for both CB units) is present at freezing.
- •A myeloablative-conditioning regimen;
- •A Lansky (for patients less than 16 years of age) or Karnofsky (for patients more than 16 years of age) score equal to or higher than 70%.
- •Adequate organ function as follows:
- •Cardiac (ejection fraction > 50%);
- •Renal (serum creatinine within the normal range for age, and creatinine clearance or a GFR > 70 ml/min/1.73m2);
- •Hepatic (AST or ALT < 5 x upper limit of normal for age);
- •Pulmonary (FEV1, FVC, and DLCO ≥ 50% by pulmonary function tests or, in children unable to cooperate, no sign of dyspnea at rest, no exercise intolerance, no supplementary oxygen therapy, and a normal pulmonary radiography or pulmonary scan);
- •No sign of uncontrolled systemic bacterial, fungal or viral infection;
- •Written informed consent by the patient or his/her legal guardian
Exclusion Criteria
- •Non-myeloablative conditioning;
- •Pregnancy or breastfeeding;
- •HIV positive serology;
- •Bone disease (e.g. osteopetrosis, osteogenesis imperfecta)
- •Previous autologous or allogeneic hematopoietic stem cell transplantation performed up to one year before enrolment, except in the case of non-engraftment or early rejection of a previous allogeneic stem cell transplantation.
- •Active skin infection at the site of intrabone injection.
- •History of intolerance/allergy to sedation medications or local anesthetics.
- •Contraindication to sedation
Outcomes
Primary Outcomes
Platelet recovery rate
Time Frame: at 100 days post- transplantation
First of seven days of untransfused platelet count higher than 20 x 10\^9/L
Secondary Outcomes
- Immunological reconstitution(at 30, 60, 100, 180, and 360 days post- transplantation)
- Neutrophil recovery rate(at 60 days post- transplantation)
- Donor chimerism rate(at 30, 60,100, and 180 days post-transplantation)
- Adverse infections (grade and frequency)(at one month post-transplantation)
- Infection rate (bacterial, viral, fungal and parasitic)(at 180 days post-transplantation)
- chronic GVHD(at 2 years post-transplantation)
- Acute GVHD (grade 2-4) rate(at 180 days)
- Event-free and overall survival(at 2 years)
Investigators
Henrique Bittencourt, MD, PhD
Hematologist - Oncologist
St. Justine's Hospital