Intrabone Infusion of Umbilical Cord Blood Stem Cells

Hematopoietic Stem Cell Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01711788
• Other study ID #: IB-UCBT
• Status: Completed
• Phase: Phase 2
• First received: October 18, 2012
• Last updated: October 3, 2017
• Start date: November 2012
• Est. completion date: October 3, 2017

Study information

• Verified date: October 2017
• Source: St. Justine's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 3, 2017
• Est. primary completion date: October 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplantation

Intervention

Procedure:
• Intrabone infusion of umbilical cord blood stem cells

Locations

Country	Name	City	State
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec

Sponsors (8)

Lead Sponsor	Collaborator
Henrique Bittencourt, MD, PhD	Elie Haddad, MD, PhD, Isabelle Louis, PhD, Marie-France Vachon, MScN, Marion Cortier, PhD, Michel Duval, MD, Pierre Teira, MD, Sonia Cellot, MD, PhD

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet recovery rate	First of seven days of untransfused platelet count higher than 20 x 10^9/L	at 100 days post- transplantation
Secondary	Neutrophil recovery rate	First of three days of absolute neutrophil count equal or higher than 0.5 x 10^9/L	at 60 days post- transplantation
Secondary	Immunological reconstitution	Total number of T cells (and subpopulations), B and NK (natural killer) cells in peripheral blood at different time-points	at 30, 60, 100, 180, and 360 days post- transplantation
Secondary	Donor chimerism rate	Percentage of donor(s) cells in peripheral blood at different time-points	at 30, 60,100, and 180 days post-transplantation
Secondary	Acute GVHD (grade 2-4) rate	Incidence of grade II-IV acute GVHD (Graft versus Host Disease)	at 180 days
Secondary	Infection rate (bacterial, viral, fungal and parasitic)	Clinical and microbiological documented infections will be reported according to anatomic site, date of onset and microorganism	at 180 days post-transplantation
Secondary	Event-free and overall survival	Event-free survival is defined as the time interval between transplantation and relapse, graft rejection, death or last follow-up, whichever occurs first; Overall survival is defined as the time between transplantation and death or last follow-up	at 2 years
Secondary	Adverse infections (grade and frequency)	Toxicity will be assessed using the Common Terminology Criteria for Adverse Events v4.0	at one month post-transplantation
Secondary	chronic GVHD	Incidence of chronic GVHD (Graft versus Host Disease) will be scored according to NIH consensus on chronic GVHD	at 2 years post-transplantation