Severe Thalassemia
Conditions
Keywords
Thalassemia, Alemtuzumab, Hematopoietic cell transplant, non-myeloablative
Brief summary
This study is being done to determine if blood cell transplants, with either bone marrow or cord blood from unrelated donors, are effective in children with severe thalassemia and if this treatment approach has acceptable risks and side effects. This study includes a preparative regimen with Hydroxyurea, Alemtuzumab, Fludarabine, Thiotepa and Melphalan that provides intense host immunosuppression without myeloablation. The primary hypothesis is that this regimen will promote stable engraftment of unrelated donor hematopoietic cells, support normal erythropoiesis, and result in an event free survival of \> 75% of children with thalassemia major.
Interventions
DRUGTransplant conditioning regimen of alemtuzumab, fludarabine, and melphalan
Days -50 to -21: Hydroxyurea 30mg/kg po Day -22: Alemtuzumab 3mg IV Day -21: Alemtuzumab 10mg IV Day -20: Alemtuzumab 15mg IV Day -19: Alemtuzumab 20mg IV Day -8: Fludarabine 30mg/m2 IV Day -7: Fludarabine 30mg/m2 IV Day -6: Fludarabine 30mg/m2 IV Day -5: Fludarabine 30mg/m2 IV Day -4: Fludarabine 30mg/m2 IV Day -4: Thiotepa 8mg/kg IV Day -3: Melphalan 140mg/m2 IV Day 0: Stem cell infusion
Sponsors
Carelon Research
Pediatric Blood and Marrow Transplant Consortium
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* 1-16.00 years old * Have transfusion dependent thalassemia major * Shall not have an HLA-matched family donor * Must have a suitably matched unrelated marrow donor or UCB product * Lansky score \>/= 70 * Adequate pulmonary, renal, liver, and other organ function as defined in protocol * Negative pregnancy test * Adequate total nucleated cell or CD34+ dose of product as defined in protocol * Iron chelation must be discontinued \>/= 48 hours prior to conditioning regimen
Exclusion criteria
* Pregnant or breastfeeding * HIV positive * Prior allogeneic marrow or stem cell transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: Event-free Survival at 1 Year. | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Development of Graft Versus Host Disease (GVHD) | 2 years |
| Median Time to ANC Engraftment | 100 days |
| Median Time to Platelet Engraftment | 100 days |
| Incidence of Disease Recurrence | 2 years |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 11 academic medical centers. The first participant was enrolled in May 2010 and the last participant was enrolled in April 2012.
Participants by arm
| Arm | Count |
|---|---|
| Conditioning Regimen Hydroxyurea days -50 to -21 Alemtuzumab days -21 to -19 Fludarabine days -8 to -4 Thiotepa day -4 Melphalan day -3 Stem cell infusion day 0
Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan: Days -50 to -21: Hydroxyurea 30mg/kg po Day -22: Alemtuzumab 3mg IV Day -21: Alemtuzumab 10mg IV Day -20: Alemtuzumab 15mg IV Day -19: Alemtuzumab 20mg IV Day -8: Fludarabine 30mg/m2 IV Day -7: Fludarabine 30mg/m2 IV Day -6: Fludarabine 30mg/m2 IV Day -5: Fludarabine 30mg/m2 IV Day -4: Fludarabine 30mg/m2 IV Day -4: Thiotepa 8mg/kg IV Day -3: Melphalan 140mg/m2 IV Day 0: Stem cell infusion | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Conditioning Regimen |
|---|---|
| Age, Continuous | 10 years |
| Race/Ethnicity, Customized Race/Ethnicity African American | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 3 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Middle Eastern | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity More than 1 race reported | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Pakistani | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Vietnamese | 1 Participants |
| Region of Enrollment United States | 21 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 21 |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 10 / 21 |
Outcome results
Primary
Primary Objective: Event-free Survival at 1 Year.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conditioning Regimen | Primary Objective: Event-free Survival at 1 Year. | 17 Participants |
Secondary
Development of Graft Versus Host Disease (GVHD)
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Conditioning Regimen | Development of Graft Versus Host Disease (GVHD) | Participants who developed any GVHD | 12 Participants |
| Conditioning Regimen | Development of Graft Versus Host Disease (GVHD) | Participants who did not develop any GVHD | 9 Participants |
Secondary
Incidence of Disease Recurrence
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conditioning Regimen | Incidence of Disease Recurrence | 1 Participants |
Secondary
Median Time to ANC Engraftment
Time frame: 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conditioning Regimen | Median Time to ANC Engraftment | 14 days |
Secondary
Median Time to Platelet Engraftment
Time frame: 100 days
Population: 3 participants did not engraft platelets
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conditioning Regimen | Median Time to Platelet Engraftment | 27.5 days |