Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503)

Completed · Phase 2

Conditions studied: Sickle Cell Disease

In brief

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.

Key facts

Study ID

NCT02766465

Run by

Medical College of Wisconsin

People needed

138

Starts

2017-03-16

Expected to finish

2023-08-02

Last updated by the study team

2025-04-18

Who can join

Age: 15 and older, up to 40. Sex: any. Healthy volunteers: not accepted.

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:
• Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory. Participants are not excluded if the serum conjugated (direct) bilirubin is >2x the upper limit of normal for age as per local laboratory and: There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR there is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin < 5 times ULN and not caused by underlying hepatic diseasePatients
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal as per local laboratory.
• Additional inclusion required for donor arm participants to proceed with transplant
• Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (≤ 90 days prior to initiation of transplant conditioning).
• Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating transplant conditioning. Subjects with clinical or radiologic evidence of a recent neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation
• Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.

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.

Where it is running

• Benioff Children's Hospital at Oakland — Oakland, California, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• University of Florida Gainsville — Gainesville, Florida, United States
• Foundation for Sickle Cell Research/Florida Sickle Inc. — Hollywood, Florida, United States
• University of Miami — Miami, Florida, United States
• Grady Memorial Hospital — Atlanta, Georgia, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Emory University — Atlanta, Georgia, United States
• Augusta University Medical Center — Augusta, Georgia, United States
• University of Iowa — Iowa City, Iowa, United States
• Children's Hospital of New Orleans — New Orleans, Louisiana, United States
• Dana Farber Cancer Institute/Brigham & Women's Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute/Massachusetts General Hospital — Boston, Massachusetts, United States
• Boston University — Boston, Massachusetts, United States
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States
• Washington University/St. Louis Children's Hospital — St Louis, Missouri, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Newark Beth Israel Medical Center — Newark, New Jersey, United States
• New York Presbyterian Brooklyn Methodist Hospital — Brooklyn, New York, United States
• Cohen Children's Medical Center — New Hyde Park, New York, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Weill Cornell Medical College — New York, New York, United States
• Montefiore Medical Center/Albert Einstein School of Medicine — The Bronx, New York, United States
• University of North Carolina Hospital at Chapel Hill — Chapel Hill, North Carolina, United States
• Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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