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

This study is currently recruiting participants. (see Contacts and Locations)
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
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

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 September 18, 2014