Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503)
STRIDE2
A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults With Severe Sickle Cell Disease (BMT CTN 1503)
2 other identifiers
interventional
138
1 country
35
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2017
Longer than P75 for phase_2
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 6, 2016
CompletedFirst Posted
Study publicly available on registry
May 9, 2016
CompletedStudy Start
First participant enrolled
March 16, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 2, 2023
CompletedResults Posted
Study results publicly available
September 24, 2024
CompletedApril 18, 2025
April 1, 2025
6.1 years
May 6, 2016
June 7, 2024
April 11, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment
Due to incomplete accrual, there was not adequate statistical power to analyze the primary endpoint as specified. Instead, point estimates for the observed proportion of patients surviving at two years post-biologic assignment in each arm were generated descriptively, with 95% CI, using the Kaplan Meier methodology. The event of interest was death from any cause.
2 Years
Secondary Outcomes (29)
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest
2 Years
Change in 6-minute Walk Distance (6MWD) Assessment From Baseline
Baseline, 2 years
Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline
Baseline, 2 years
Change in Albuminuria Assessment From Baseline
Baseline, 2 years
Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline
Baseline, 2 years
- +24 more secondary outcomes
Study Arms (2)
Donor Arm
EXPERIMENTALDonor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft
No-Donor Arm
ACTIVE COMPARATORNo-donor arm patients will continue with standard of care per their SCD physician.
Interventions
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.
Sirolimus at therapeutic doses through day 180, then taper per institutional guidelines if donor CD3+ \>50%
G-CSF 5 μg/kg/day continue until neutrophil engraftment.
Eligibility Criteria
You may qualify if:
- Age ≥ 15 and \< 41 years
- Severe sickle cell disease \[Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ) genotype\] with at least 1 of the following manifestations (a-e):
- Clinically significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours;
- History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy);
- An average of three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
- Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
- An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
- Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months as defined as ONE or more of the following: Chronic pain without contributory SCD complications, OR Mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
- i. High impact chronic pain is identified as those reporting "severe interference" with life activities OR "usually or always" experiencing a limitation of their life or work activities including household chores. (See guidelines for identifying HICP in the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely to contributory SCD complications is excluded.
- Adequate physical function as measured by all of the following:
- Karnofsky/Lansky performance score ≥ 60
- Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
- Pulmonary function:
- a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the lung for carbon monoxide (DLCO) \> 40% (corrected for hemoglobin) d. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance \>70 mL/min; or GFR \> 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR).
- e. Hepatic function:
- +5 more criteria
You may not qualify if:
- HLA typing with a donor search prior to referral (consultation with HCT physician).
- If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time, and also did not have an unrelated donor search, the patient will be considered eligible.
- If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
- If a subject has had HLA typing with no related donor search and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
- Subjects with a known HLA-identical sibling or HLA-matched unrelated donor are excluded
- Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
- Seropositivity for HIV.
- Previous HCT or solid organ transplant.
- Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
- A history of substance abuse as defined by version IV of the Diagnostic \& Statistical Manual of Mental Disorders (DSM IV).
- Demonstrated lack of compliance with prior medical care as determined by referring physician.
- Pregnant or breast feeding females.
- Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical College of Wisconsinlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- Dana-Farber Cancer Institutecollaborator
- National Marrow Donor Programcollaborator
- Emory Universitycollaborator
Study Sites (35)
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
Related Publications (3)
Walters MC, Eapen M, Liu Y, El Rassi F, Waller EK, Levine JE, Strouse JJ, Antin JH, Parikh SH, Bakshi N, Dampier C, Jaroscak JJ, Bergmann S, Wong T, Kota V, Pace B, Lekakis LJ, Lulla P, Nickel RS, Kasow KA, Popat U, Smith W, Yu L, DiFronzo N, Geller N, Kamani N, Klings ES, Hassell K, Mendizabal A, Sullivan K, Neuberg D, Krishnamurti L. Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease. Blood Adv. 2025 Mar 11;9(5):955-965. doi: 10.1182/bloodadvances.2024013926.
PMID: 39471440RESULTLeonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.
PMID: 36240296DERIVEDKrishnamurti L, Neuberg DS, Sullivan KM, Kamani NR, Abraham A, Campigotto F, Zhang W, Dahdoul T, De Castro L, Parikh S, Bakshi N, Haight A, Hassell KL, Loving R, Rosenthal J, Smith SL, Smith W, Spearman M, Stevenson K, Wu CJ, Wiedl C, Waller EK, Walters MC. Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Am J Hematol. 2019 Apr;94(4):446-454. doi: 10.1002/ajh.25401. Epub 2019 Feb 11.
PMID: 30637784DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Company, LLC
Study Officials
- STUDY DIRECTOR
Mary Eapen, MD
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 6, 2016
First Posted
May 9, 2016
Study Start
March 16, 2017
Primary Completion
May 2, 2023
Study Completion
August 2, 2023
Last Updated
April 18, 2025
Results First Posted
September 24, 2024
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).