Ph I/II Study of Allogeneic SCT for Clinically Aggressive Sickle Cell Disease (SCD)

• Status: Recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy.

Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Alemtuzumab; Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• Patients with sickle cell disease, subtype Hgb SS, SC, or SB disease who are on chronic transfusion therapy for a prior stroke or those patients who were intolerant of hydroxyurea therapy or were being treated with hydroxyurea therapy and were complicated by at least one of the following:

• Stroke or central nervous system event lasting longer than 24 hours

• Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year severe enough to interfere with the patient's normal daily function or require medical attention in the clinic, emergency room, acute care center, or hospital

• Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits

• Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events

• Red-cell alloimmunization (≥ 2 antibodies) during longterm transfusion therapy

• Bilateral proliferative retinopathy with major visual impairment in at least one eye

• Osteonecrosis of 2 or more joints

• Sickle cell nephropathy

• Stage I or II sickle lung disease

• Symptoms of pulmonary hypertension and mean pulmonary artery pressure > 25mmHg

• Age 16-60 years

• Karnofsky performance status of 70 or higher

• Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%

• Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50%

• Estimated GFR ≥ 30mL/min as calculated by the modified MDRD equation

• ALT ≤ 3x upper limit of normal

• No evidence of chronic active hepatitis or cirrhosis

• HIV-negative

• Patient is not pregnant

• History of compliance with medications and medical care

• Patient is able and willing to sign informed consent

• Patient has an HLA-identical matched related donor