MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Event-free Survival
研究概览
简要总结
This is a single-institution, phase II study to determine the event-free survival at 1 year post allogeneic transplant and serial mesenchymal stem cell (MSC) infusions from a related donor (HLA identical, mismatched or haploidentical) or matched unrelated donor for the biochemical correction of severe epidermolysis bullosa (EB).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of severe form of EB characterized by collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis).
- •Adequate organ function within 4 weeks of study registration defined as:
- •Renal: glomerular filtration rate within normal range for age
- •Hepatic: Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal
- •Pulmonary: adequate pulmonary function in the opinion of the enrolling investigator
- •Cardiac: left ventricular ejection fraction ≥ 45%, normal EKG or approved by Cardiology for transplant
- •Sexually active participants must agree to use adequate birth control for the during the study period (from before the start of the preparative chemotherapy through 1 year post-transplant)
- •Available donor per section 5: targeted MFI < 1,000 (MFI exceeding 1000 must be approved by the PI and treatment team.)
- •Voluntary written consent - adult or parent (with information sheet for minors, if applicable) prior to any research related procedures or treatment
排除标准
- •beta 3 laminin JEB mutants
- •Active untreated systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
- •History of HIV infection
- •Evidence of squamous cell carcinoma
- •Pregnant or breast feeding. Females of child-bearing potential must have a negative pregnancy test prior to study registration as the agents administered in this study are Pregnancy Category C and D.
研究组 & 干预措施
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Thymoglobulin (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Cyclophosphamide (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Fludarabine (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Total Body Irradiation (Radiation)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Thymoglobulin (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Bone marrow infusion (Procedure)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Tacrolimus (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Mycophenolate Mofetil (Drug)
RDEB: HCT plus MSC Arm B
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Donor mesenchymal stem cell infusions (Biological)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Thymoglobulin (Drug)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Cyclophosphamide (Drug)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Fludarabine (Drug)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Total Body Irradiation (Radiation)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Bone marrow infusion (Procedure)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Tacrolimus (Drug)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Mycophenolate Mofetil (Drug)
JEB: HCT plus MSC Arm B
Junctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Donor mesenchymal stem cell infusions (Biological)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Thymoglobulin (Drug)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Cyclophosphamide (Drug)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Fludarabine (Drug)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Total Body Irradiation (Radiation)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Bone marrow infusion (Procedure)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Tacrolimus (Drug)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Mycophenolate Mofetil (Drug)
RDEB: HCT Plus MSC Arm E
Recessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
干预措施: Donor mesenchymal stem cell infusions (Biological)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Cyclophosphamide (Drug)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Fludarabine (Drug)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Total Body Irradiation (Radiation)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Bone marrow infusion (Procedure)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Tacrolimus (Drug)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Mycophenolate Mofetil (Drug)
HCT with 300 cGy of TBI Arm A
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
干预措施: Donor mesenchymal stem cell infusions (Biological)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Thymoglobulin (Drug)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Cyclophosphamide (Drug)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Fludarabine (Drug)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Total Body Irradiation (Radiation)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Bone marrow infusion (Procedure)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Tacrolimus (Drug)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Mycophenolate Mofetil (Drug)
Re-Transplant Arm C
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
干预措施: Donor mesenchymal stem cell infusions (Biological)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Thymoglobulin (Drug)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Cyclophosphamide (Drug)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Fludarabine (Drug)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Total Body Irradiation (Radiation)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Bone marrow infusion (Procedure)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Tacrolimus (Drug)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Mycophenolate Mofetil (Drug)
HCT Arm D
HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
干预措施: Donor mesenchymal stem cell infusions (Biological)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Thymoglobulin (Drug)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Cyclophosphamide (Drug)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Fludarabine (Drug)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Total Body Irradiation (Radiation)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Bone marrow infusion (Procedure)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Tacrolimus (Drug)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Mycophenolate Mofetil (Drug)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Donor mesenchymal stem cell infusions (Biological)
HCT Alone Arm F
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Busulfan (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Thymoglobulin (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Cyclophosphamide (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Fludarabine (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Total Body Irradiation (Radiation)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Bone marrow infusion (Procedure)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Tacrolimus (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Mycophenolate Mofetil (Drug)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Donor mesenchymal stem cell infusions (Biological)
HCT plus MSC Arm G
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
干预措施: Busulfan (Drug)
结局指标
主要结局
Event-free Survival
时间窗: 1 year post-transplant
An event defined as death or a 50% increase in a patient's IScoreEB from baseline
次要结局
- Change of a Patient's iscorEB(1 year post-transplant)
- Transplant-related Mortality(180 days post-transplant)
- Average Change in Quality of Life(2 years post-transplant)
- Lymphoid Chimerism(Day 28, 60, 100, 180, and year 1 and 2 post-transplant)
- Myeloid Chimerism(Day 28, 60, 100, 180, and year 1 and 2 post-transplant)
- Average Change of a Patient's iscorEB(2 year post-transplant)