Stem Cell Transplant for Hemoglobinopathy

• Status: Completed
• Trial end date: 2020-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This study tests the clinical outcomes of one of two preparative regimens (determined by available donor source) in patients with non-malignant hemoglobinopathies. The researchers hypothesize that these regimens will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease.

Regimen A2 has replaced Regimen A in this study. Two patients were treated on Regimen A but did not have evidence of initial engraftment thus triggering the stopping rule for that arm of this study.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborator: National Marrow Donor Program
• Treatments: Alemtuzumab; Antilymphocyte Serum; Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Lenograstim; Sargramostim; Vidarabine

Criteria

Inclusion Criteria:

• Patients with Sickle Cell Disease/Thalassemia (SCD/THAL) 0-50 years of age with an acceptable stem cell donor and disease characteristic defined by the following:

• Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing

• Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions

• Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,

• Impaired neuropsychological function and abnormal cerebral MRI scan

• Stage I or II sickle lung disease,

• Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value)

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

• Osteonecrosis of multiple joints with documented destructive changes

• Requirement for chronic transfusions but with red blood cell (RBC) alloimmunization >2 antibodies during long term transfusion therapy

• Patients with transfusion dependent alpha- or beta-thalassemia 0-35 years of age with an acceptable stem cell donor as defined in the criteria in section above.

• Patients with other non-malignant hematologic disorders that are transfusion-dependent or involve other potentially life-threatening cytopenias (including but not limited to Severe Congenital Neutropenia, Diamond-Blackfan Anemia and Shwachman-Diamond Syndrome) who are 0-35 years of age with an acceptable stem cell donor

• Second Transplants

• Patients with sickle cell disease or thalassemia who have failed to engraft or have autologous recovery after a myeloablative SCT regimen or non-myeloablative regimen are eligible for this protocol.

• Regimen A2 will be utilized for patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or for any patient who has pre-existing organ dysfunction making them ineligible for a myeloablative preparative regimen.

• Regimen B will be utilized for patients with sickle cell disease or thalassemia who have an HLA-identical sibling donor.

• Patients must meet above criteria.

• If the patient has received prior radiation therapy, eligibility to receive additional radiation therapy must be determined by Dr. Dusenbery

• If first transplant was a non-myeloablative regimen, the second transplant can occur at any time

• If the first transplant was a myeloablative regimen, then the second transplant must be > 6 months from the first transplant

Exclusion Criteria:

• Patients with one or more of the following:

• Karnofsky or Lansky performance score <70

• Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy

• Stage III-IV lung disease

• GFR<30% predicted

• Pregnant or lactating females

• Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity

• Psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance

• Patients not able to receive total lymphocytic irradiation (TLI) due to prior radiation therapy