The purpose of this study is to find out whether siplizumab is safe and effective for patients with SCD undergoing an allogeneic transplant and to prevent development of Graft versus Host Disease (GVHD) and graft failure. The main goals of this study are :
* To determine if acute GVHD occurs and how severe the acute GVHD is in subjects receiving the study drug
* To determine if graft failure occurs in subjects receiving the study drugs
In this study, participants will receive 5 infusions of the study drug, siplizumab, while getting a stem cell transplant for SCD. Before siplizumab infusion, participants will be given medications to reduce the risks of allergic reaction to the drug.
Who can participate
Age range18 Years ā 50 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
ā. Patients with sickle cell anemia (Hb SS, SĪ²0 thalassemia or severe SC) who are 18 - 50 years of age inclusive AND who have 1 or more of the following:
ā. Clinically significant neurologic event (stroke) or any neurological deficit lasting at least 24 hours. Stroke will be defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy.
ā. History of two or more episodes of ACS in the 2-year period preceding enrollment despite supportive care measures (i.e. asthma therapy and/or hydroxyurea).
ā. History of three or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
ā. Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year for 1 year or more to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and ACS)
ā. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity \> or equal to 2.7 m/sec or pulmonary hypertension diagnosed by right heart catheterization.
ā. Chronic kidney disease including patients on hemo-dialysis
. Recurrent tricorporal priapism defined as at least 2 episodes of an erection last ā„4 hours involving the corpus cavernosa and corpus spongiosa.
Exclusion criteria
ā. Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 35% of predicted OR baseline oxygen saturation of \<85% or oxygen pressure in arterial blood (PaO2) \<70.
ā. Severe cardiac dysfunction defined as ejection fraction \<45% or subjects who have been receiving chronic transfusion therapy for \> 1 year and have evidence of iron overload (serum ferritin levels \>1000 ng/mL), a cardiac MRI is required. Cardiac T2\* \<10 ms results in exclusion.
ā. Liver iron content (LIC) ā„15 mg Fe/g dry weight on R2 MRI of liver, unless liver biopsy within 3 months prior to or at screening shows no evidence of bridging fibrosis or cirrhosis. Presence of bridging (portal to portal) fibrosis or cirrhosis in liver biopsy OR transaminases \>5x normal upper limit (ULN) for age or direct bilirubin \>3x normal upper limit (ULN).
ā. Clinical stroke within 6 months of anticipated transplant
ā. Karnofsky performance score \< 50%
ā. HIV infection
ā. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment.
ā. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT in the opinion of the investigator.