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Recruiting Phase 2

Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell Antibody

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About this study

This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.

Condition
Sickle Cell Disease
Tested
Daratumumab, Alemtuzumab, Sirolimus, Total Body Irradiation
Sponsor
Children's National Research Institute

Who can join

Age
2 to 25 years
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 24

  • Minimum age: 2 years
  • Maximum age: 25 years
  • Study condition: Sickle Cell Disease
  • General:
  • Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens.
  • Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L.
  • Lansky/Karnofsky score of, at least, 70.
  • Patients with genotypes hemoglobin SS and Sβ0 thalassemia must have at least one of the following:
  • History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions.
  • Progression of CNS vasculopathy on MRA determined to be secondary to SCD.
  • History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images).
  • History of two or more episodes of Acute Chest Syndrome (ACS) in lifetime.
  • History of three or more SCD pain events requiring treatment with an opiate or IV pain medication in lifetime.
  • History of any hospitalization for a complication secondary to SCD (does NOT include empiric hospitalizations for fever only).
  • History of two or more episodes of priapism.
  • Administration of regular RBC transfusions (≥8 transfusions episodes in the previous 12 months).
  • At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
  • Patients with all other sickle genotypes (e.g. hemoglobin SC, Sβ+ thalassemia, etc.) must have at least one of the following:
  • Clinically significant neurologic event (overt stroke).
  • History of two or more episodes of ACS in the 2-year period preceding enrollment.
  • History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment.
  • History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment.
  • History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
  • Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months)

Exclusion 10

  • Life expectancy less than 6 month
  • Pregnant or breastfeeding patients.
  • Infectious Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning.
  • Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.
  • Patients with confirmed seropositivity for HIV and patients with active or resolved Hepatitis B or C determined by serology and/or NAAT are excluded.
  • Liver: Direct (conjugated) bilirubin \> 1.5 mg/dL. Transaminases \>5x upper limit of normal for age.
  • Cardiac: Left ventricular shortening fraction \<25% or ejection fraction \<50% by ECHO. Uncontrolled cardiac arrhythmia.
  • Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2.
  • Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) \<35% (adjusted for hemoglobin). Baseline oxygen saturation \<94% at rest or PaO2 \<70. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
  • Heme: Available, medically suitable, and equivalent HLA-matched sibling donor, who does not have major ABO incompatibility or express RBC antigens against which the patient is alloimmunized.

Where

1 site, 1 recruiting

Children's National Hospital

Washington D.C., District of Columbia, United States

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.