Haploidentical Transplantation With Pre-Transplant Immunosuppressive Therapy for Patients With Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- Biological: Hematopoietic stem cell transplantation
- Registration Number
- NCT03279094
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease.
The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.
- Detailed Description
All patients will receive an haploidentical hematopoietic stem cell transplant with the following conditioning and GvHD prevention:
Pre-transplant immunosuppressive therapy:
2 cycles of Fludarabine and Dexamethasone x 5 days each cycle
Conditioning regimen:
rATG daily x 3 days, Fludarabine daily x 6 days and Busulfan daily x 4 days
GVHD prophylaxis:
Cyclophosphamide day +3 and +4, Tacrolimus and Mycophenolate mofetil
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 11
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Haploidentical stem cell transplantation Hematopoietic stem cell transplantation -
- Primary Outcome Measures
Name Time Method Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT: 190 days * Rate of death of any causes
* Rate of study discontinuation or early withdrawal
* Rate of graft failure
• Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve \<30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
* Rate of grade 4 non-hematological toxicities per NCI CTCAE v4.03 that last more than 21 days
- Secondary Outcome Measures
Name Time Method Incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation 100 days after transplantation Percent of donor chimerism at 12 and 24 months after HCT 12 and 24 months after HCT Disease free survival rate 24 months • Disease free survival: the time from HCT to death, secondary graft failure, or last follow-up, whichever comes first.
Immune reconstitution at day 100, 180 and 365 24 months • Immune reconstitution: measurement of CD3, CD4, CD8, CD11b, CD14, CD56, CD20/19, FoxP3+ Treg, and memory subsets.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 from start of pre-transplant immunosuppressive therapy to 24 months post transplant 24 months post-transplant Rate of graft failure 24 months Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve \<30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
Event-free survival rate 24 months • Event-free survival: the time from start of PTIS to death, the unacceptable events, or last follow-up, whichever comes first.
Time to donor neutrophil engraftment 24 months Day of Neutrophil Engraftment: The first of three consecutive days on which the ANC is ≥0.5x109/L
Time to donor platelets engraftment 24 months Day of Platelet engraftment: The first documented day on which the platelet count is \>20x109/L unsupported by platelet transfusions for 7 days
Overall survival rate 24 months • Overall survival: the time from start of PTIS to death, or last follow-up, whichever comes first.
Incidence of chronic GvHD 24 months Change From Baseline in Pain Scores using Numerical Rating Scale or Faces Pain Rating Scale at 100 days, 6 months and 12 months post-transplant 100 days, 6 months and 12 months post-transplant
Trial Locations
- Locations (1)
City of Hope Medical Center
🇺🇸Duarte, California, United States