Clinical trial NCT00153985: Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies
Official title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemoglobinopathies
Sickle Cell Disease
Thalassemia
Keywords: Hemoglobinopathies
Sickle cell anemia
sickle cell-hemoglobin C disease
sickle cell-B-thalassemia
transfusion-dependant thalassemia
allogeneic transplant
nonmyeloablative transplant
Stem cell transfusion
graft vs. host disease
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
name: Brigham and Women's Hospital
name: Emory University
name: Feist-Weiller Cancer Center at Louisiana State University Health Sciences
name: Ohio State University
First posted: 2005-09-12
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if treatment with reduced-dose busulfex, fludarabine and alemtuzumab (CAMPATH) followed by sten cell infusion will allow for donor stem cells to grow in patients with hemoglobinopathies bone marrow and restore circulating blood counts. In addition the incidence and severity of side effects and of graft vs. host disease (GVHD) will be monitored.

Detailed description: * In order to undergo transplant procedure, patients will be admitted to the hospital for approximately 10-14 days.
* To prepare patient's bone marrow to accept donor stem cells, they will receive fludarabine and busulfex. Fludarabine will be given intravenously once daily for 4 days. Busulfex will be given once daily for the same 4 days.
* One day before patients receive busulfex and fludarabine, they will also be given alemtuzumab intravenously once daily for 5 days.
* Three days after the end of chemotherapy, patients will receive the infusion of donor stem cells.
* If patients have thalassemia, they will receive subcutaneous injections of filgrastim starting on day one after the donor stem cell transfusion and will continue receiving filgrastim every day until it appears that the donor stem cells have been accepted. If the patient has sickle cell disease, filgrastim will not be given,
* Additional drugs will be given to help prevent infection (i.e. antibiotics).
* After stem cell infusion patients will be examined and have blood tests weekly for 1 month. Bone marrow biopsies, and blood work will also be performed 1 month, 3 months, 6 months and 1 year after stem cell infusion.
* Patients will be on the study for about 12 months. After study is completed progress will be monitored on an annual basis.

Eligibility criteria: Inclusion Criteria:

* Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive.
* Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens.

Exclusion Criteria:

* Pregnancy
* Acute hepatitis
* Cardiac ejection fraction \< 30%
* Severe renal impairment
* Severe residual functional neurologic impairment
* Evidence of HIV infection

Primary outcomes:
measure: Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
timeFrame: 3 years
Secondary outcomes:
measure: Solid Organ Toxicity Related to the Conditioning Regimen.
timeFrame: 3 years
measure: The Incidence of Grade II-IV Acute Graft vs. Host Disease.
timeFrame: 3 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute-Emory University
state: Georgia
city: Shreveport
country: United States
facility: Feist-Weiller Cancer Center-LSU
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State University College of Medicine
state: Ohio
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Catherine J. Wu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Sep;36(9):1205-15. doi: 10.1016/j.exphem.2008.04.004. Epub 2008 Jun 11.