Maintaining a Higher Level of Haemoglobin: Effect on the White Cells After Bone Marrow Transplantation in Children.

This study has been terminated.
(3 unexpected Serious Adverse Events (veno-occlusive disease (VOD)))
Sponsor:
Collaborator:
Nancy Robitaille, MD
Information provided by:
St. Justine's Hospital
ClinicalTrials.gov Identifier:
NCT00937053
First received: July 9, 2009
Last updated: August 3, 2010
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Neutropenia
Other: Transfusion level 120 g/dL
Other: Transfusion level 70 g/dL
Other: Platelet transfusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Maintaining a Higher Haemoglobin Level on Neutropenia Duration After Bone Marrow Transplantation in Children.

Resource links provided by NLM:


Further study details as provided by St. Justine's Hospital:

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). [ Time Frame: First 100 days post HSCT ] [ Designated as safety issue: Yes ]

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)). [ Time Frame: First 100 days post HSCT ] [ Designated as safety issue: No ]
  • Transfusions given (red cells and platelets) [ Time Frame: First 100 days post HSCT ] [ Designated as safety issue: No ]
  • Hospitalization length [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Immune reconstitution (lymphoid subsets) [ Time Frame: First 100 days post HSCT ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Graft vs host disease (GVHD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Treatment-related mortality (death without relapse) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Chimerism [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: June 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hemoglobin below 120 g/dL Other: Transfusion level 120 g/dL
Patients whose hemoglobin falls below 120 g/dL will be transfused with red cells within 24 hours.
Other: Platelet transfusion
Patients whose platelets fall below 10 x 10*9 will be transfused with platelets
Active Comparator: Hemoglobin below 70 g/dL Other: Transfusion level 70 g/dL
Patients whose hemoglobin falls below 70 g/dL will be transfused with red cells within 24 hours
Other: Platelet transfusion
Patients whose platelets fall below 10 x 10*9 will be transfused with platelets

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.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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)
  2. Patients planned to undergo a related or unrelated allogeneic bone marrow transplant for a malignant or benign disease (except for sickle cell disease)
  3. 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
  4. 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
  5. Patient must agree to receive blood transfusion
  6. Patient (or their legal guardians) must sign an Informed consent Form

Exclusion Criteria:

  1. Patients receiving autologous bone marrow transplant, cord blood transplant or peripheral stem cell transplant
  2. Sickle cell disease (since higher hemoglobin level increases blood viscosity and puts these patients at risk for stroke)
  3. 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)
  4. Presence of an allo-antibody directed against red blood cells
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00937053

Locations
Canada, Alberta
Souther Alberta Children's Cancer Care Program, Calgary
Calgary, Alberta, Canada
Canada, British Columbia
Pediatric Bone Marrow Transplant Unit, British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Canada, Ontario
Section of Blood and Marrow Transplant, The Hospital for Sick Children
Toronto, Ontario, Canada
Canada, Quebec
Department of Hematology, The Montreal Children's Hospital
Montreal, Quebec, Canada
Hematopoietic Stem Cell Transplantation Program, Sainte-Justine Hospital
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
St. Justine's Hospital
Nancy Robitaille, MD
Investigators
Principal Investigator: Michel Duval, MD St. Justine's Hospital
Principal Investigator: Nancy Robitaille, MD St. Justine's Hospital
  More Information

No publications provided

Responsible Party: Michel Duval, CHU Sainte-Justine, Research Center
ClinicalTrials.gov Identifier: NCT00937053     History of Changes
Other Study ID Numbers: 9967
Study First Received: July 9, 2009
Last Updated: August 3, 2010
Health Authority: Canada: Health Canada and FRSQ (Québec)

Keywords provided by St. Justine's Hospital:
Neutropenia
Transfusions
Hemoglobin
Bone marrow transplant
Hematopoietic stem cell transplant

Additional relevant MeSH terms:
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on October 19, 2014