Intrabone Infusion of Umbilical Cord Blood Stem Cells

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

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.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Procedure: Intrabone infusion of umbilical cord blood stem cells

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3C1T5
      • Centre Hospitalier Universitaire Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrabone umbilical cord blood tranplant; Intrabone infusion of umbilical cord blood stem cells	Procedure: Intrabone infusion of umbilical cord blood stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet recovery rate	First of seven days of untransfused platelet count higher than 20 x 10^9/L	at 100 days post- transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Donor chimerism rate	Percentage of donor(s) cells in peripheral blood at different time-points	at 30, 60,100, and 180 days post-transplantation
Acute GVHD (grade 2-4) rate	Incidence of grade II-IV acute GVHD (Graft versus Host Disease)	at 180 days
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
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
Adverse infections (grade and frequency)	Toxicity will be assessed using the Common Terminology Criteria for Adverse Events v4.0	at one month post-transplantation
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

Collaborators and Investigators

• Sponsor: Henrique Bittencourt, MD, PhD
• Collaborators: Michel Duval, MD; Pierre Teira, MD; Sonia Cellot, MD, PhD; Isabelle Louis, PhD; Elie Haddad, MD, PhD; Marie-France Vachon, MScN; Marion Cortier, PhD
• Investigators: Principal Investigator: Henrique Bittencourt, MD, PhD, St. Justine's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): October 3, 2017
• Study Completion (Actual): October 3, 2017

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 18, 2012
• First Posted (Estimate): October 22, 2012

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Pediatric patients; Hematopoietic stem cells; Umbilical cord blood transplantation; Neutrophil recovery; Platelet recovery; Intrabone infusion
• Other Study ID Numbers: IB-UCBT