The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.

Condition	Treatment or Intervention	Phase
Hemoglobinopathies Anemia, Sickle Cell Hemoglobin SC Disease Thalassemia Thalassemia Major	Drug: Busulfex  Drug: fludarabine  Procedure: nonmyeloablative conditioning for stem cell transplantation	Phase II

Further Study Details: 

Expected Total Enrollment:  20

Hemoglobinopathies, such as sickle cell disease and thalassemia major, are genetic diseases associated with significant morbidity and premature death. Allogeneic bone marrow transplantation (BMT) is the only potential cure for severe hemoglobinopathies. Typical regimens have used high doses of chemotherapy or chemo-radiotherapy to ablate recipient hematopoiesis and to prevent graft rejection. The widespread use of this treatment has been limited by toxicity, risk of end-organ damage, and donor availability. This study will use a non-myeloablative regimen of fludarabine and Busulfex to attempt to generate consistent engraftment with donor hematopoietic stem cells in patients with severe hemoglobinopathy.

G-CSF mobilization of the donor’s peripheral blood white blood cells will precede donor apheresis. A non-myeloablative conditioning regimen of fludarabine and Busulfex will be administered to patients prior to allogeneic peripheral blood stem cell infusions. FK506 and prednisone will be administered for graft versus host disease prophylaxis. Patients will be evaluated for engraftment, donor:host hematopoietic chimerism, toxicity, and hemoglobinopathy.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

--All patients must:

• Have related donors who are identical at 6 HLA loci (A, B and DR) by molecular typing
• Have a performance status from 0-2
• Give written informed consent

--Patients with sickle cell disease should have 1 or more of the following:

• Acute chest syndrome requiring recurrent hospitalization or exchange transfusion
• Nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours
• Recurrent vaso-occlusive pain (2 episodes or more per year) or recurrent priapism
• Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50 percent of normal predicted value)
• Bilateral proliferative retinopathy and major visual impairment in at least 1 eye
• Osteonecrosis of multiple joints

--Patients with thalassemia should have 1 or more of the following:

• Transfusion dependence, defined as a transfusion requirement of greater than or equal to 6 units of packed red blood cells over the past 12 months
• Iron overload, defined as serum ferritin greater than 500 in the absence of infection or biopsy-proven iron overload
• Presence of 2 or more alloantibodies against red cell antigens

Exclusion criteria:

• Pregnancy
• Acute hepatitis (transaminases greater than 3 times the normal value)
• Cardiac ejection fraction less than 30 percent
• Severe renal impairment (glomerular filtration rate less than 30 percent of predicted normal value)
• Severe residual functional neurologic impairment (other than hemiplegia alone)
• Seropositivity for HIV

Catherine J. Wu, MD      (617) 632-5943    cwu@partners.org

Massachusetts
      Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital, Boston,  Massachusetts,  02115,  United States; Recruiting

Study chairs or principal investigators

Catherine J. Wu, MD,  Principal Investigator,  Dana-Farber Cancer Institute, Harvard Medical School   

Study ID Numbers:  DAIT DF/HCC 01-098; P01 A 129530
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  April 30, 2002
ClinicalTrials.gov Identifier:  NCT00034528
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08