Clinical trial NCT01711788: Intrabone Infusion of Umbilical Cord Blood Stem Cells
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematopoietic Stem Cell Transplantation
Keywords: Hematopoietic stem cells
Umbilical cord blood transplantation
Intrabone infusion
Platelet recovery
Neutrophil recovery
Pediatric patients
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Michel Duval, MD
name: Pierre Teira, MD
name: Sonia Cellot, MD, PhD
name: Isabelle Louis, PhD
name: Elie Haddad, MD, PhD
name: Marie-France Vachon, MScN
name: Marion Cortier, PhD
First posted: 2012-10-22
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Platelet recovery rate
timeFrame: at 100 days post- transplantation
Secondary outcomes:
measure: Neutrophil recovery rate
timeFrame: at 60 days post- transplantation
measure: Immunological reconstitution
timeFrame: at 30, 60, 100, 180, and 360 days post- transplantation
measure: Donor chimerism rate
timeFrame: at 30, 60,100, and 180 days post-transplantation
measure: Acute GVHD (grade 2-4) rate
timeFrame: at 180 days
measure: Infection rate (bacterial, viral, fungal and parasitic)
timeFrame: at 180 days post-transplantation
measure: Event-free and overall survival
timeFrame: at 2 years
measure: Adverse infections (grade and frequency)
timeFrame: at one month post-transplantation
measure: chronic GVHD
timeFrame: at 2 years post-transplantation
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Henrique Bittencourt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vairy S, Louis I, Vachon MF, Richer J, Teira P, Cellot S, Villeneuve E, Haddad E, Duval M, Bittencourt H. Intrabone infusion for allogeneic umbilical cord blood transplantation in children. Bone Marrow Transplant. 2021 Aug;56(8):1937-1943. doi: 10.1038/s41409-021-01275-0. Epub 2021 Apr 6.