Overview

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