A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Anemia and Other Hemoglobinopathies
2 Years
70 Years
Both
Sickle Cell Disease
Trial Information
A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Anemia and Other Hemoglobinopathies
OBJECTIVES:
- Determine the transplant-related mortality and progression-free survival of patients
with severe hemoglobinopathies receiving nonmyeloablative conditioning comprising
fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by
partially HLA-mismatched bone marrow transplantation from first-degree relatives or
HLA-matched donors.
- Characterize donor hematopoietic chimerism at 30, 60, and 180 days after
transplantation in these patients.
- Determine the hematologic and non-hematologic toxicity of this regimen in these
patients.
OUTLINE:
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days
-6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients also
undergo total-body irradiation on day -1.
- Bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on
day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Donors
receive filgrastim (G-CSF) subcutaneously beginning on day -5 to day -1.
- Graft-versus-host disease prophylaxis: Patients receive sirolimus orally daily on days
5-365 and oral mycophenolate mofetil 3 times a day on days 5-35.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following sickle cell anemias (Hb SS):
- Hb S/β° thalassemia
- Hb S/β+ thalassemia
- Hb SC disease
- Hb SE disease
- Hb SD disease
- Hemoglobin SO-Arab disease
- Hb S/hereditary persistence of fetal hemoglobin
- Meets 1 of the following criteria:
- History of invasive pneumococcal disease
- Stroke or CNS event lasting > 24 hours
- MRI changes indicative of brain parenchymal damage
- Evidence of cerebrovascular disease by magnetic resonance angiography
- Acute chest syndrome requiring exchange transfusion or hospitalization
- Recurrent vaso-occlusive pain crisis (> 2 per year for the last 2 years)
- Stage I or II sickle lung disease
- Sickle retinopathy
- Osteonecrosis
- Red cell alloimmunization (> 2 antibodies) during long-term transfusion
- Constellation of dactylitis in the first year of life AND a baseline hemoglobin
< 7 g/dL and leukocytosis (WBC > 13.4/mm^3) in the absence of infection during
the second year of life
- Pitted RBC count > 3.5% during the first year of life
- Ineligible for or refused bone marrow transplantation from an HLA-matched sibling
donor
- Partially mismatched (at least haploidentical) first-degree relative donor available
- No minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor
is available
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 OR Karnofsky or Lansky PS 70-100%
- LVEF ≥ 35%
- FEV_1 and forced vital capacity ≥ 40% predicted
- Direct bilirubin < 3.1 mg/dL
- No moderate to severe pulmonary hypertension by ECHO
- No debilitating medical or psychiatric illness that would preclude study
participation
- No HIV positivity
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior transfusions from donor
- No immunosuppressive agents, including steroids as antiemetics, within 24 hours after
the last dose of post-transplantation cyclophosphamide
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT)
Outcome Time Frame:
1 year after bone marrow transplant
Safety Issue:
No
Principal Investigator
Javier Bolanos-Meade, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
J0676 CDR0000540593
NCT ID:
NCT00489281
Start Date:
May 2007
Completion Date:
Related Keywords:
- Sickle Cell Disease
- sickle cell disease
- Anemia, Sickle Cell
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
