RECRUITINGPhase 2INTERVENTIONAL

Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease

A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease

About This Trial

The study is a Phase II clinical trial. Patients will receive intensity modulated total body irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplant (HSCT). The primary objective of the study is to determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.

Who May Be Eligible (Plain English)

Patient Eligibility: 1. Patients with sickle cell disease are eligible if they have any of the following complications: 1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, hospital admissions, or home bedrest leading to absence from work or school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle cell nephropathy, defined by a GFR \< 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin \> 300 mg/g creatinine) 1.9 Pulmonary hypertension, defined by a mean pulmonary arterypressure \>25mmHg 2. Age 16-60 years 3. Karnofsky performance status of 60 or higher (Appendix A) 4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% 5. Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration) 6. Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation 7. ALT ≤ 3x upper limit of normal 8. HIV-negative 9. Patient is not pregnant 10. Patient is able and willing to sign willing to sign a consent form 11. Patient does not have a fully HLA-matched sibling donor 12. Patient has an HLA-haploidentical relative ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Patient Eligibility: 1. Patients with sickle cell disease are eligible if they have any of the following complications: 1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, hospital admissions, or home bedrest leading to absence from work or school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle cell nephropathy, defined by a GFR \< 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin \> 300 mg/g creatinine) 1.9 Pulmonary hypertension, defined by a mean pulmonary arterypressure \>25mmHg 2. Age 16-60 years 3. Karnofsky performance status of 60 or higher (Appendix A) 4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% 5. Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration) 6. Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation 7. ALT ≤ 3x upper limit of normal 8. HIV-negative 9. Patient is not pregnant 10. Patient is able and willing to sign informed consent 11. Patient does not have a fully HLA-matched sibling donor 12. Patient has an HLA-haploidentical relative Donor Eligibility Relatives (parents, offspring, siblings, aunts/uncles, cousins) will be tested by molecular typing of HLA class I (A, B, and C) and class II (DRB1) at low resolution. Only those that are an HLA-haploidentical match (≥ 4/8) will be considered as a potential donor. NOTE: If during testing, a fully HLA-matched sibling donor is found and is willing to donate his/her stem cells, the potential subject will not be eligible for this protocol. Donor consent will be obtained as per standard protocol of the bone marrow transplant unit.

Treatments Being Tested

DRUG

ATG

0.5 mg/kg IV on day -9, and 2 mg/kg on days -8 and day -7

DRUG

fludarabine

30 mg/m2 IVPB daily for day -6 (6 days before stem cell infusion) through day -2

DRUG

cyclophosphamide

14.5 mg/kg IV on days -6 and -5 and 50 mg/kg/d on days +3 and +4

RADIATION

Total body irradiation

3 Gy on day -1

PROCEDURE

Stem cell infusion

Stem cell product infused according to BMT unit policy on day 0.

DRUG

Sirolimus

loading dose of 15 mg followed by 5 mg per day on day +5

DRUG

mycophenolate mofetil

1 g every 8 h (until day 35) will be started on day 5

Locations (1)

University of Illinois at Chicago

Chicago, Illinois, United States