Clinical Trial
Study Details
A:
Busulfan dose will be 3.2 mg/kg administered as a single daily dose IV on days -8 through -5 with dosing adjusted using targeted pharmacokinetics.
A:
Fludarabine dose will be 35 mg/m\^2/day administered IV on days -7 through -3 (total fludarabine dose is 175 mg/m\^2).
C:
Fludarabine 30mg/m2 IV dose will be given on Days -8, -7, -6, -5, -4
A:
r-ATG will be administered IV on day -6 at 0.5mg/kg, on day -5 at 1 mg/kg and on days -4, -3 and -2 at 1.5mg/kg (total r-ATG dose is 6 mg/kg).
A,B,C:
Day 0 is the day of transplantation.
A:
Tacrolimus commences on day -3 and extends through day +180 after transplantation with doses adjusted to maintain appropriate levels according to institutional guidelines.
C:
Tacrolimus at therapeutic doses through Day 180, then taper per institutional guidelines
A:
Methotrexate will be administered intravenously on day+1 at 15mg/m\^2, day+3 at 10mg/m\^2, day+6 at 10mg/m\^2, and day+11 at 10mg/m\^2.
C:
Methotrexate IV 7.5 mg/m2 dose will be given on Days +1, 3, +6 following transplant
Continue to receive standard of care treatment per patient's SCD physician.
B:
Alemtuzumab 0.03 mg/kg IV dose will be given on Day -7, Alemtuzumab 0.1 mg/kg IV dose will be given on Day -6, Alemtuzumab 0.3 mg/kg IV dose will be given on Day -5,-4,-3
C:
Alemtuzumab test dose 3 mg IV once 24 hours prior to 1st dose of Alemtuzumab Alemtuzumab 10 mg IV, 15 mg IV, 20 mg IV given on Days -22 through Day -18. Alemtuzumab doses may be administered between Days -22 and -18 but are required to be on three consecutive days.
Total Body Irradiation 300 cGY on Day -2
Sirolimus at therapeutic doses through day 180, then taper per institutional guidelines if donor CD3+ \>50%
C:
Melphalan 140 mg/m2 IV dose will be given on Day -3
G-CSF 5 μg/kg/day continue until neutrophil engraftment.
This is a clinical trial that will compare survival and sickle related outcomes in adolescents and young adults with severe sickle cell disease after bone marrow transplantation and standard of care. The primary outcome is 2-year overall survival.
Study Overview
This is a prospective phase II multi-center trial of hematopoietic stem cell transplantation or standard of care based on availability of HLA-matched related or unrelated donor after confirmation of clinical eligibility. In order to minimize bias assignment to either treatment arm, clinical eligibility to both treatment arms are similar and donor availability is not known at referral. HLA typing and donor search is initiated upon confirmation of clinical eligibility for the study. Additionally, all analyses of primary and secondary endpoints will follow the Intent-to-Treat principle to address potential bias introduced by participants with donors not proceeding to transplantation or those without a matched donor receiving transplantation with less well-matched donors.
The primary outcome is 2-year overall survival. Our hypothesis is that patients who receive bone marrow transplantation will experience early deaths but that this will plateau by 2 years after transplantation. Patients who receive standard of care will not experience early death but will succumb to their disease at a rate much higher than the general population. Therefore, the goal of the study is to establish that the difference in the proportion of patients surviving is not significantly more than 15% lower in the donor arm at 2-years after assignment to treatment arm.
Secondary endpoints will compare changes in sickle cell disease related events (pulmonary hypertension, cerebrovascular events, renal function, avascular necrosis, leg ulcer) and functional outcomes \[6-minute walk distance (6MWD), health-related quality of life, cardiac function, pulmonary function, and mean pain intensity as assessed by a multidimensional electronic pain diary\] from baseline to 2-years after assignment to treatment arms.
Additionally for patients assigned to the donor arm and expected to undergo transplantation, hematopoietic recovery, graft rejection, acute and chronic graft-versus-host disease, other significant transplant-related complications and disease-free survival will be reported.
Contacts and Locations
Benioff Children's Hospital at Oakland
Oakland, California 94609
United States
Children's National Medical Center
Washington D.C., District of Columbia 20010
United States
University of Florida Gainsville
Gainesville, Florida 32611
United States
Foundation for Sickle Cell Research/Florida Sickle Inc.
Hollywood, Florida 33021
United States
University of Miami
Miami, Florida 33136
United States
Grady Memorial Hospital
Atlanta, Georgia 30303
United States
Children's Healthcare of Atlanta
Atlanta, Georgia 30322
United States
Emory University
Atlanta, Georgia 30322
United States
Augusta University Medical Center
Augusta, Georgia 30912
United States
University of Iowa
Iowa City, Iowa 52242
United States
Children's Hospital of New Orleans
New Orleans, Louisiana 70118
United States
Dana Farber Cancer Institute/Brigham & Women's Hospital
Boston, Massachusetts 02114
United States
Dana Farber Cancer Institute/Massachusetts General Hospital
Boston, Massachusetts 02115
United States
Boston University
Boston, Massachusetts 02215
United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Washington University/St. Louis Children's Hospital
St Louis, Missouri 63110
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
New York Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York 11215
United States
Cohen Children's Medical Center
New Hyde Park, New York 11040
United States
Icahn School of Medicine at Mount Sinai
New York, New York 10029
United States
Weill Cornell Medical College
New York, New York 10065
United States
Montefiore Medical Center/Albert Einstein School of Medicine
The Bronx, New York 10467
United States
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina 27516
United States
Duke University Medical Center
Durham, North Carolina 27705
United States
Ohio State University
Columbus, Ohio 43210
United States
University of Oklahoma
Oklahoma City, Oklahoma 73104
United States
Oregon Health Sciences University
Portland, Oregon 97239
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
Medical University of South Carolina
Charleston, South Carolina 29425
United States
University of Texas Health Sciences Center
Houston, Texas 77004
United States
Baylor College of Medicine/The Methodist Hospital
Houston, Texas 77030
United States
University of Texas/MD Anderson CRC
Houston, Texas 77030
United States
University of Virginia
Charlottesville, Virginia 22908
United States
Virginia Commonwealth University
Richmond, Virginia 23298
United States