Hemoglobinopathies, Sickle Cell Disease, Thalassemia
Conditions
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
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.
Interventions
DRUGBusulfex
Given once daily for 4 days
DRUGFludarabine
Given intravenously once daily for 4 days
DRUGAlemtuzumab
One day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.
PROCEDUREStem Cell Transfusion
Performed three days after the end of chemotherapy
Sponsors
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Brigham and Women's Hospital
Emory University
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Ohio State University
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. | 3 years | Outcome was measured by ANC \>500 for three consecutive days prior to day 30 after PBSC infusion, \>25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and \>25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Solid Organ Toxicity Related to the Conditioning Regimen. | 3 years | Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab. |
| The Incidence of Grade II-IV Acute Graft vs. Host Disease. | 3 years | Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion. |
Countries
United States
Participant flow
Recruitment details
Activated for enrollment 3/4/2004. Closed to enrollment 4/25/2008. Participating institutions included: Dana-Farber Cancer Institute, Boston, Massachusetts, Feist-Weiller Cancer Center, LSU Health Sciences Center, Shreveport, Louisiana and Winship Cancer Institute, Emory University, Atlanta, Georgia
Pre-assignment details
All enrolled patients received a stem cell transplant.
Participants by arm
| Arm | Count |
|---|---|
| Transplant for Severe Hemoglobinopathies Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Transplant for Severe Hemoglobinopathies |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age Continuous | 25 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Outcome was measured by ANC \>500 for three consecutive days prior to day 30 after PBSC infusion, \>25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and \>25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.
Time frame: 3 years
Population: All patients enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transplant for Severe Hemoglobinopathies | Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. | 2 participants |
Secondary
Solid Organ Toxicity Related to the Conditioning Regimen.
Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
Time frame: 3 years
Population: All patients enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transplant for Severe Hemoglobinopathies | Solid Organ Toxicity Related to the Conditioning Regimen. | 2 participants |
Secondary
The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.
Time frame: 3 years
Population: All patients enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transplant for Severe Hemoglobinopathies | The Incidence of Grade II-IV Acute Graft vs. Host Disease. | 2 participants |