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Intraosseous Infusion of Unrelated Cord Blood Grafts

This study has been terminated.
(poor enrollment)
Sponsor:
Information provided by (Responsible Party):
John Horan, Emory University
ClinicalTrials.gov Identifier:
NCT00967525
First received: August 11, 2009
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

In this trial the investigators seek to determine if injecting cord blood cells directly into the bone marrow (intraosseous injection), rather than infusing them intravenously, can improve engraftment. The rational for doing this is that most hematopoietic stem cells (HSCs) infused intravenously never reach the bone marrow, getting trapped by other organs, such as the lungs, instead. The potential advantage of intraosseous infusion is suggested by studies in rodents that have demonstrated that in HSC transplants where the cell dose is limiting intraosseous injection is a more effective route of administration. The safety of intraosseous injections, in general, is underscored by the vast experience using intraosseous injections for resuscitation of critically ill children. The safety of injecting HSCs intraosseously has been demonstrated in a clinical trial of transplanting bone marrow cells.

To safeguard against problems that might result, if intraosseous infusion fails to improve engraftment in this trial, the investigators will integrate a recently introduced strategy proven to improve engraftment-the transplantation of two cord blood units. Transplanting two unrelated cord blood units by intravenous infusion has been shown to improve engraftment (although there is still room for improvement). In this trial one unit will be injected intraosseously and the other unit will be infused intravenously.

This study is being conducted as a forerunner to a larger, multi-center trial. The investigators intend to enroll five patients over 1-2 years.


Condition Intervention
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
Myelodysplastic Syndrome
Procedure: cord blood infusion

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Intraosseous Infusion of Unrelated Cord Blood Grafts

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Compare the rapidity of myeloid engraftment of intraosseously and intravenously administered unrelated cord blood grafts. [ Time Frame: 1 year after last patient enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Obtain preliminary data using flow cytometric analysis to assess the importance of graft associated variables that may affect engraftment. [ Time Frame: 1 year after last patient enrolled ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: March 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Receive two cord blood units. One administered by intraosseous infusion and the other by intravenous infusion. The second unit is being given as a safeguard, but will also allow the researchers to directly compare engraftment between intravenously and intraosseously infused cord blood units.
Procedure: cord blood infusion
Receive two cord blood units. One administered by intraosseous infusion and the other by intravenous infusion. The second unit is being given as a safeguard, but will also allow the researchers to directly compare engraftment between intravenously and intraosseously infused cord blood units.

Detailed Description:

Hematopoietic (blood forming) stem cells (HSCs) reside primarily in the bone marrow. Traditionally, HSCs have been obtained directly from the bone marrow. Transplants using cells obtained this way are referred to as bone marrow transplants. HSCs also circulate in the blood. Transplants using cells obtained from the blood of children and adults are referred to as peripheral blood stem cell transplants. The blood of fetuses is especially rich in HSCs and these cells can be easily collected at birth from the placenta. Transplants using these cells are called cord blood transplants. Although HSCs can be collected from various sites, all HSC transplants, regardless of the source, are given to recipients by intravenous infusion. The transplanted HSCs then migrate to the bone marrow.

Over the past ten years unrelated cord blood transplantation has become an accepted alternative to bone marrow transplantation. African-Americans and other minorities, who are underrepresented in the National Marrow Donor Program, have benefited particularly from this. In infants and young children cord blood transplantation appears to be as effective as bone marrow transplantation. In older children, adolescents and adults, however, cord blood transplantation has not been as effective, primarily because most cord blood units provide an insufficient number of cells to ensure prompt and reliable engraftment ("taking" of the transplanted cells in the recipient's bone marrow).

  Eligibility

Ages Eligible for Study:   36 Months to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 36 months to 60 years old (YO)
  2. No prior autologous or allogeneic transplant
  3. Karnofsky performance score or Lansky Play-Performance of at least 80

Exclusion Criteria:

  1. Age < 36 months or > 60 YO
  2. creatinine clearance or nuclear medicine GFR of < 50 mL/min
  3. cardiac ejection fraction < 50%
  4. bilirubin > 2 × upper limit of normal or ALT > 4 × upper limit of normal or unresolved veno-occlusive disease
  5. Pulmonary carbon monoxide diffusing capacity (DLCO), adjusted for Hgb < 50%
  6. Karnofsky performance score or Lansky Play-Performance Scale <80
  7. Uncontrolled viral, bacterial, or fungal infection at the time of study enrollment
  8. Seropositive for HIV
  9. Availability of a willing and well HLA matched related (genotypically identical or mismatched at a single allele or antigen defined by typing at HLA A, B, C and DRB1 loci) donor
  10. Availability of a willing and well HLA matched unrelated (allele matched or mismatched at a single allele defined by allele level typing for HLA A, B, C and DRB1 loci) adult blood or marrow donor
  11. Availability of an umbilical cord blood unit, which provides at least a 4/6 HLA match as defined above and ≥ 5.0 * 107 NC/Kg (cryopreserved)
  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: NCT00967525

Locations
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: John Horan, MD Emory University
  More Information

No publications provided

Responsible Party: John Horan, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT00967525     History of Changes
Other Study ID Numbers: IRB00000113, Intraosseous Infusion
Study First Received: August 11, 2009
Last Updated: November 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
AML
ALL
leukemia
CML
Myelodysplastic Syndrome
malignancies
Undifferentiated leukemia
High risk malignancies

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on November 24, 2014