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

  • STATUS
    Recruiting
  • End date
    May 28, 2022
  • participants needed
    15
  • sponsor
    University of Illinois at Chicago
Updated on 28 January 2021
hypertension
stroke
sirolimus
hydroxyurea
carbon monoxide
cell transplantation
hemoglobin s
blood transfusion
alemtuzumab
acute chest syndrome
priapism
chest syndrome
alloimmunization
osteonecrosis

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.

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.

Details
Condition SICKLE CELL ANEMIA, Sickle Cell Disease
Treatment Sirolimus, alemtuzumab, Allogeneic Non-Myeloablative Stem Cell Transplantation
Clinical Study IdentifierNCT01499888
SponsorUniversity of Illinois at Chicago
Last Modified on28 January 2021

Eligibility

Yes No Not Sure

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
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