Maintaining a Higher Level of Haemoglobin: Effect on the White Cells After Bone Marrow Transplantation in Children.
Primary Purpose
Neutropenia
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Transfusion level 120 g/dL
Transfusion level 70 g/dL
Platelet transfusion
Sponsored by
About this trial
This is an interventional treatment trial for Neutropenia focused on measuring Neutropenia, Transfusions, Hemoglobin, Bone marrow transplant, Hematopoietic stem cell transplant
Eligibility Criteria
Inclusion Criteria:
- Patients between 1 year of age and 18 years of age at the time of transplantation (18 years is the upper limit of childhood in CIBMTR definitions)
- Patients planned to undergo a related or unrelated allogeneic bone marrow transplant for a malignant or benign disease (except for sickle cell disease)
- Conditioning regimen must be myeloablative, i.e. include busulfan greater or equal to 12 mg/kg or Total Body Irradiation greater or equal to 10 Gy, except for patients with acquired severe aplastic anemia
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrolment in the trial
- Patient must agree to receive blood transfusion
- Patient (or their legal guardians) must sign an Informed consent Form
Exclusion Criteria:
- Patients receiving autologous bone marrow transplant, cord blood transplant or peripheral stem cell transplant
- Sickle cell disease (since higher hemoglobin level increases blood viscosity and puts these patients at risk for stroke)
- Hematopoietic growth factor (G-CSF, GM-CSF, stem cell factor, erythropoietin) planned before transplantation (post-transplant decision of hematopoietic growth factors administration as required by the patient's condition will be accepted)
- Presence of an allo-antibody directed against red blood cells
Sites / Locations
- Souther Alberta Children's Cancer Care Program, Calgary
- Pediatric Bone Marrow Transplant Unit, British Columbia Children's Hospital
- Section of Blood and Marrow Transplant, The Hospital for Sick Children
- Hematopoietic Stem Cell Transplantation Program, Sainte-Justine Hospital
- Department of Hematology, The Montreal Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Hemoglobin below 120 g/dL
Hemoglobin below 70 g/dL
Arm Description
Outcomes
Primary Outcome Measures
Time to neutrophil engraftment (defined as the time from transplantation to the first of three consecutive days with a neutrophil count > 0,5 x 109/L, as used in the International Bone Marrow Transplant Registry (IBMTR) criteria).
Secondary Outcome Measures
Time to platelet engraftment (defined as the time from transplantation to the first of three consecutive days with a platelet count > 20 x 109/L, without platelet transfusion 7 days prior (IBMTR criteria)).
Transfusions given (red cells and platelets)
Hospitalization length
Immune reconstitution (lymphoid subsets)
Overall survival
Graft vs host disease (GVHD)
Treatment-related mortality (death without relapse)
Relapse
Chimerism
Full Information
NCT ID
NCT00937053
First Posted
July 9, 2009
Last Updated
August 3, 2010
Sponsor
St. Justine's Hospital
Collaborators
Nancy Robitaille, MD
1. Study Identification
Unique Protocol Identification Number
NCT00937053
Brief Title
Maintaining a Higher Level of Haemoglobin: Effect on the White Cells After Bone Marrow Transplantation in Children.
Official Title
The Effect of Maintaining a Higher Haemoglobin Level on Neutropenia Duration After Bone Marrow Transplantation in Children.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2009
Overall Recruitment Status
Terminated
Why Stopped
3 unexpected Serious Adverse Events (veno-occlusive disease (VOD))
Study Start Date
June 2009 (undefined)
Primary Completion Date
June 2010 (Anticipated)
Study Completion Date
June 2015 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
St. Justine's Hospital
Collaborators
Nancy Robitaille, MD
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine if maintaining a high hemoglobin level in children that underwent bone marrow transplant will accelerate the neutrophil recovery.
Detailed Description
The investigators know that children requiring bone marrow transplant need to first go through a myeloablative regimen, which induces a neutropenia. The length of the neutropenia has an incidence on the risk of contracting bacterial and fungal infections that could be lethal. It is then important to find ways to accelerate the neutrophil recovery, so patient survival can be improved.
Studies conducted in the '70s and '80s suggested that if the hemoglobin level could be kept at a higher level, then the neutrophil recovery would be accelerated. Other studies also support the hypothesis that if the stem cells do not need to produce red cells because these are being supplied through transfusions, then the stem cells would differentiate into non-erythroid cell lines.
As of now, for patients undergoing a bone marrow transplant, it is standard practice to transfuse with red cells based on the condition of the patient or if the hemoglobin level falls below 70 g/L. Hematopoietic growth factors have been used to increase the speed of the neutrophil recovery, but studies conducted so far do not demonstrate that mortality and length of hospitalization have been reduced by the specific use of G-CSF. In more recent studies, these agents have been shown to also have negative effects, such as delayed platelet recovery and impaired immune recovery. In addition, the prophylactic use of G-CSF was also associated with graft-versus-host disease, treatment-related mortality and death.
In conclusion, this study will determine if maintaining a higher hemoglobin level has an effect on the neutrophil recovery after allogenic bone marrow transplantation in children.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neutropenia
Keywords
Neutropenia, Transfusions, Hemoglobin, Bone marrow transplant, Hematopoietic stem cell transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hemoglobin below 120 g/dL
Arm Type
Experimental
Arm Title
Hemoglobin below 70 g/dL
Arm Type
Active Comparator
Intervention Type
Other
Intervention Name(s)
Transfusion level 120 g/dL
Intervention Description
Patients whose hemoglobin falls below 120 g/dL will be transfused with red cells within 24 hours.
Intervention Type
Other
Intervention Name(s)
Transfusion level 70 g/dL
Intervention Description
Patients whose hemoglobin falls below 70 g/dL will be transfused with red cells within 24 hours
Intervention Type
Other
Intervention Name(s)
Platelet transfusion
Intervention Description
Patients whose platelets fall below 10 x 10*9 will be transfused with platelets
Primary Outcome Measure Information:
Title
Time to neutrophil engraftment (defined as the time from transplantation to the first of three consecutive days with a neutrophil count > 0,5 x 109/L, as used in the International Bone Marrow Transplant Registry (IBMTR) criteria).
Time Frame
First 100 days post HSCT
Secondary Outcome Measure Information:
Title
Time to platelet engraftment (defined as the time from transplantation to the first of three consecutive days with a platelet count > 20 x 109/L, without platelet transfusion 7 days prior (IBMTR criteria)).
Time Frame
First 100 days post HSCT
Title
Transfusions given (red cells and platelets)
Time Frame
First 100 days post HSCT
Title
Hospitalization length
Time Frame
2 years
Title
Immune reconstitution (lymphoid subsets)
Time Frame
First 100 days post HSCT
Title
Overall survival
Time Frame
5 years
Title
Graft vs host disease (GVHD)
Time Frame
2 years
Title
Treatment-related mortality (death without relapse)
Time Frame
2 years
Title
Relapse
Time Frame
2 years
Title
Chimerism
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients between 1 year of age and 18 years of age at the time of transplantation (18 years is the upper limit of childhood in CIBMTR definitions)
Patients planned to undergo a related or unrelated allogeneic bone marrow transplant for a malignant or benign disease (except for sickle cell disease)
Conditioning regimen must be myeloablative, i.e. include busulfan greater or equal to 12 mg/kg or Total Body Irradiation greater or equal to 10 Gy, except for patients with acquired severe aplastic anemia
Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrolment in the trial
Patient must agree to receive blood transfusion
Patient (or their legal guardians) must sign an Informed consent Form
Exclusion Criteria:
Patients receiving autologous bone marrow transplant, cord blood transplant or peripheral stem cell transplant
Sickle cell disease (since higher hemoglobin level increases blood viscosity and puts these patients at risk for stroke)
Hematopoietic growth factor (G-CSF, GM-CSF, stem cell factor, erythropoietin) planned before transplantation (post-transplant decision of hematopoietic growth factors administration as required by the patient's condition will be accepted)
Presence of an allo-antibody directed against red blood cells
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel Duval, MD
Organizational Affiliation
St. Justine's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nancy Robitaille, MD
Organizational Affiliation
St. Justine's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Souther Alberta Children's Cancer Care Program, Calgary
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Pediatric Bone Marrow Transplant Unit, British Columbia Children's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Section of Blood and Marrow Transplant, The Hospital for Sick Children
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Hematopoietic Stem Cell Transplantation Program, Sainte-Justine Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Department of Hematology, The Montreal Children's Hospital
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Maintaining a Higher Level of Haemoglobin: Effect on the White Cells After Bone Marrow Transplantation in Children.
We'll reach out to this number within 24 hrs