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

This study is currently recruiting participants.
Verified January 2014 by University of Pittsburgh
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Lakshmanan Krishnamurti, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01565616
First received: March 26, 2012
Last updated: January 17, 2014
Last verified: January 2014
  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 University of Pittsburgh:

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: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01565616

Contacts
Contact: Lakshmanan Krishnamurti, MD 412-692-6059 krislx@chp.edu
Contact: Melissa A Byrne, MPH, RN 412-692-7336 Melissa.Jones@chp.edu

Locations
United States, California
Children's Hospital of Oakland Recruiting
Oakland, California, United States, 94609
Contact: Cyrus Bascon    510-597-7169    CBascon@mail.cho.org   
Principal Investigator: Mark C Walters, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Lauren Prosser    202-476-5774    lprosser@cnmc.org   
Principal Investigator: Allistair Abraham, MD         
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Nohelia Gonzalez    305-243-5100    ngonzalez5@med.miami.edu   
Principal Investigator: Lazaros John Lekakis, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Rebecca Gerkin    404-778-0400    rgerkin@emory.edu   
Principal Investigator: Edmund Waller, MD         
Principal Investigator: James Eckman, MD         
Georgia Regents University Not yet recruiting
Augusta, Georgia, United States, 30912
Contact: Leigh Wells    706-723-4335    lwells@georgiahealth.edu   
Principal Investigator: Jeremy Pantin, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Rachel Young    734-615-2858    younggrl@umich.edu   
Principal Investigator: James Connelly, MD         
Principal Investigator: Andrew Campbell, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Stacy Murray    919-668-1211    stacy.murray@duke.edu   
Principal Investigator: Keith Sullivan, MD         
United States, Pennsylvania
Chidren's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Melissa A Byrne, MPH, RN    412-692-7336    Melissa.Jones@chp.edu   
Principal Investigator: Lakshmanan Krishnamurti, MD         
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Kathryn Candler    804-828-4732    kcandler@vcu.edu   
Principal Investigator: Christina Wiedl, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Lakshmanan Krishnamurti, MD Children's Hospital of Pittsburgh of UPMC
  More Information

Additional Information:
No publications provided

Responsible Party: Lakshmanan Krishnamurti, Principal Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01565616     History of Changes
Other Study ID Numbers: PRO10110484, 1R34HL108761-01
Study First Received: March 26, 2012
Last Updated: January 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Bone Marrow Transplant
Severe Sickle Cell Disease
HCT
Hematopoietic Stem Cell Therapy
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 April 17, 2014