NCT01499888

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

Phase I/II Study of Allogeneic Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease (SCD)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: University of Illinois at Chicago · Academic / Other
• Sex: All
• Age: 16 Years – 60 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Sickle cell disease is an inherited defect caused by a mutation in the Beta globin gene affecting red blood cells. Symptoms begin at 6 months of life and often lead to debilitating vaso-occlusive pain crises, acute insults to vital organ systems,chronic organ injury, and decreased survival with median survival estimated at 42 years for men and 48 years for women. Several cohort studies have identified clinical and laboratory predictors for decreased survival which include acute complications, and chronic complications of sickle cell disease. Hydroxyurea is the only FDA approved drug to help ameliorate symptoms associated with sickle cell disease. Two nonrandomized studies have suggested a reduction in mortality after 17 years of long term hydroxyurea treatment. However, the mortality rate is still high in the hydroxyurea cohort at 43.1% and only 38.1% of patients have a rise in fetal hemoglobin indicating that a significant percentage of patients still have aggressive disease despite hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of pulmonary hypertension. In the pediatric population, patients that have not clinically improved despite optimized hydroxyurea management are offered allogeneic stem cell transplantation. Until recently, the options were more limited in adults with sickle cell disease that had aggressive disease despite hydroxyurea therapy. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Up to 50% of patients with sickle cell disease who are on chronic transfusion therapy will develop allo-antibodies making further transfusions difficult with a high potential for hemolytic transfusion reactions. Patients with sickle cell disease often have chronic underlying organ disease and so the effects of chemotherapy may be unpredictable and potentially more harmful, making low dose TBI more attractive as a safer modality for conditioning. 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. An optional correlative trial will be conducted to compare ocular findings after stem cell transplantation with those findings before stem cell transplantation. Anterior and posterior ocular examination as well as objective tests will be performed on subjects.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Non-Myeloablative Stem Cell Transplantation	Alemtuzumab-based non-myeloablative allogeneic hematopoietic stem cell transplantation using immune-suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy. Transplant regimen Day -7 to -3: Alemtuzumab (1mg/kg, total dose) divided over the 5 days, IVPB over 2 hours daily Day -3 until 100% chimerism obtained: Sirolimus dosed for target trough level of 10-15 ng/mL Day -2: Total body irradiation with 300cGy Day 0: Stem cell infusion
DRUG	Alemtuzumab	In this protocol, patients will be given alemtuzumab 1mg/kg divided equally over five days with the maximum dose of 20mg per day.
DRUG	Sirolimus	On day -1, patients will receive a loading dose of 12 mg followed by 4 mg per day. Subsequent dosing will be based on clinical toxicity, GVHD concurrent medications, medical conditions, prior drug levels, drug-drug interactions, and blood levels with target of 3 to 12 ng/mL.

Timeline

• Start date: 2011-11-11
• Primary completion: 2028-09-23
• Completion: 2029-10-01
• First posted: 2011-12-26
• Last updated: 2025-04-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study