Bone Marrow Transplantation in Young Adults With Severe Sickle Cell Disease (STRIDE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Lakshmanan Krishnamurti, Emory University
ClinicalTrials.gov Identifier:
NCT01565616
First received: March 26, 2012
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
The primary goal of this multicenter study is to determine the safety and feasibility of a Bone Marrow Transplantation (BMT) in young adults with severe sickle cell disease (SCD) using a reduced toxicity conditioning regimen consisting of busulfan (Bu)/ fludarabine (Flu)/ anti-thymocyte globulin (ATG). A two-component design will be used for this study. The first component will be restricted to patients who have an HLA-identical sibling donor. Five patients will be enrolled during the first component of the study. The second component of enrollment will include patients who have a related or an unrelated HLA-matched donor. Up to 10 additional patients will be enrolled in this component of the study.

Condition Intervention Phase
Sickle Cell Disease
Other: Biological: Bone Marrow Transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Hematopoietic Stem Cell Therapy for Young Adults With Severe Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To determine the safety and feasibility of a Bone Marrow Transplantation (BMT) in young adults with severe sickle cell disease (SCD) using a reduced toxicity conditioning regimen. Event-free survival (EFS) at one year after BMT will be evaluated by determining disease status, engraftment, and mortality.


Secondary Outcome Measures:
  • Transplant-related outcomes [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    The secondary objectives of this protocol are to evaluate the effect of a BMT on the clinical course of patients with severe SCD and determining the incidence of other transplant-related outcomes.

    Specifically, to determine whether pre-transplant organ dysfunction (brain, heart, lung, kidney, liver, spleen, etc) due to SCD can be reversed after a BMT and the incidence of survival, engraftment, GVHD, and other transplant-related conditions.



Estimated Enrollment: 15
Study Start Date: March 2012
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Biological: Bone Marrow Transplant
Patients undergoing bone marrow transplant for sickle cell disease
Other: Biological: Bone Marrow Transplant

The bone marrow transplant regimen is below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant.

SCHEMA OF CONDITIONING REGIMEN Day Treatment (BU- Busulfan, FLU-Fludarabine, ATG-Rabbit Anti-thymocyte globulin)

Day -8 BU 3.2 mg/ kg/dose IV

Day -7 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV

Day -6 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 0.5mg/kg IV

Day -5 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 1.0mg/kg IV

Day -4 FLU 35mg/m2 IV, ATG 1.5mg/kg IV

Day -3 FLU 35mg/m2 IV, ATG 1.5mg/kg IV

Day -2 ATG 1.5mg/kg IV

Day -1 Rest

Day 0 Stem cell infusion

GVHD Regimen

Day -3 Calcineurin Inhibitor (Cyclosporine or Tacrolimus) therapeutic doses through day 180, then taper

Day 0 Stem cell infusion

Day +1 Methotrexate 7.5 mg/m2 IV

Day +3 Methotrexate 7.5 mg/m2 IV

Day +6 Methotrexate 7.5 mg/m2 IV

Day+11 Methotrexate 7.5 mg/m2 IV


  Eligibility

Ages Eligible for Study:   16 Years to 40 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of severe sickle cell disease is denoted by one of the following:

    • Clinically significant neurologic event or any neurological deficit lasting greater than 24 hours
    • 2 or more episodes of acute chest syndrome in the last 2 years despite the use supportive care measures
    • 3 or more severe vaso-occlusive pain episodes per year in the last 2 years despite supportive care measures
    • Receives regular RBC transfusion therapy, defined as 8 or more transfusions per year for 1 year or longer
    • Echocardiograph finding of Tricuspid Regurgitation Jet (TRJ) velocity of 2.7 m/sec or greater
  • Adequate physical function
  • Must have an 8 of 8 HLA-A, B, C, and DRB1 allele matched related or unrelated bone marrow donor

Exclusion Criteria:

  • Patients with cirrhosis of the liver, uncontrolled bacterial, viral or fungal infection in the past month, or seropositivity for HIV
  • Patients who have received prior HCT
  • Females who are pregnant or breast feeding
  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: NCT01565616

Locations
United States, California
Children's Hospital of Oakland
Oakland, California, United States, 94609
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Emory University
Atlanta, Georgia, United States, 30322
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Chidren's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Emory University
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Lakshmanan Krishnamurti, MD Emory University
  More Information

Additional Information:
Responsible Party: Lakshmanan Krishnamurti, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01565616     History of Changes
Other Study ID Numbers: IRB00068287  1R34HL108761-01 
Study First Received: March 26, 2012
Last Updated: April 11, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Severe Sickle Cell Disease
HCT
Hematopoietic Stem Cell Therapy
Bone Marrow Transplant
Hematologic Diseases
Genetic Diseases
Anemia
Hemolytic
Congenital
Human Leukocyte Antigen
HLA

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 28, 2016