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for people ages 15–40 (full criteria)
at Oakland, California and other locations
study started
estimated completion:



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.

Official Title

A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults With Severe Sickle Cell Disease (BMT CTN #1503)


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.


Sickle Cell Disease Young Adults Phase II Trial Hematopoietic Cell Transplantation (HCT) Human Leukocyte Antigen (HLA) Anemia, Sickle Cell Methotrexate Fludarabine phosphate Tacrolimus Busulfan Antilymphocyte Serum Thymoglobulin Fludarabine


You can join if…

Open to people ages 15–40

  1. Age 15.00 - 40.99 years
  2. 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):
  3. Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;
  4. 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;
  5. Three or more pain crises per year in the 2-year period preceding referral(required intravenous pain management in the outpatient or inpatient hospital setting)
  6. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusions per year for ≥ 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
  7. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥2.7 m/sec.
  8. Adequate physical function as measured by all of the following:
  9. Karnofsky/Lansky performance score > or equal to 60
  10. Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
  11. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥ 85% and Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin)
  12. 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).
  13. Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal as per local laboratory.Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or who experience a sudden, profound change in the serum hemoglobin after a RBC transfusion are not excluded.

You CAN'T join if...

  1. HLA typing prior to referral (consultation with HCT physician). However, if a subject has had HLA typing with accompanying documentation that relatives were not HLA typed and that a search of the unrelated donor registry was not performed the subject will be considered eligible. Documentation will be reviewed and adjudicated by the Protocol Officer or his/her designee.
  2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
  3. Seropositivity for HIV.
  4. Previous HCT.
  5. Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
  6. A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
  7. Demonstrated lack of compliance with prior medical care (determined by referring physician).
  8. Pregnant or breast feeding females.
  9. Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.
  10. . Unwillingness to use approved contraception method from time of biologic assignment until discontinuation of all immunosuppressive medications if assignment at biologic assignment would be to donor arm.

Additional Eligibility Criteria for Transplant after Biologic Assignment to the Donor Arm:

Participants assigned to the Donor Arm at the time of biologic assignment are subject to additional transplant eligibility criteria as specified below. Additional, repeat clinical assessments prior to transplant should be obtained in accordance with institutional policies and standards of care in the interest of good clinical practice.

  1. Participants who are receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative) will undergo liver MRI for estimation of hepatic iron content. Liver biopsy is indicated for hepatic iron content ≥7 mg Fe/gm liver dry weight. Histological examination must document the absence of cirrhosis, bridging fibrosis and active hepatitis. The absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleagues (1995) as described in the Manual of Operating Procedures.
  2. Cerebral MRI/MRA within 30 days prior to initiation of transplant conditioning. If there is clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) subjects will be deferred for at least 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation.
  3. Absence of donor specific HLA antibodies (section 2.5)
  4. 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.
  5. The HLA-matched donor must be medically fit to donate and willing to donate bone marrow.


  • Benioff Children's Hospital at Oakland accepting new patients
    Oakland, California, 94609, United States
  • Stanford University not yet accepting patients
    Stanford, California, 94305, United States


accepting new patients
Start Date
Completion Date
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network Website
National Marrow Donor Program
Phase 2
Study Type
Last Updated
August 29, 2017
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