MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs
Phase 2
Completed
- Conditions
- Epidermolysis Bullosa
- Interventions
- Radiation: Total Body IrradiationProcedure: Bone marrow infusionBiological: Donor mesenchymal stem cell infusions
- Registration Number
- NCT02582775
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
Inclusion Criteria
-
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
Exclusion Criteria
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RDEB: HCT plus MSC Arm B Thymoglobulin 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). RDEB: HCT plus MSC Arm B Cyclophosphamide 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). RDEB: HCT plus MSC Arm B Fludarabine 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). HCT with 300 cGy of TBI Arm A Total Body Irradiation Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. RDEB: HCT plus MSC Arm B Total Body Irradiation 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). RDEB: HCT plus MSC Arm B Bone marrow infusion 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). RDEB: HCT plus MSC Arm B Donor mesenchymal stem cell infusions 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). JEB: HCT plus MSC Arm B Total Body Irradiation 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). JEB: HCT plus MSC Arm B Bone marrow infusion 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). JEB: HCT plus MSC Arm B Donor mesenchymal stem cell infusions 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). RDEB: HCT Plus MSC Arm E Total Body Irradiation 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). RDEB: HCT Plus MSC Arm E Bone marrow infusion 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). RDEB: HCT Plus MSC Arm E Donor mesenchymal stem cell infusions 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). HCT with 300 cGy of TBI Arm A Bone marrow infusion Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. HCT with 300 cGy of TBI Arm A Donor mesenchymal stem cell infusions Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. Re-Transplant Arm C Total Body Irradiation Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. Re-Transplant Arm C Bone marrow infusion Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. Re-Transplant Arm C Donor mesenchymal stem cell infusions Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. HCT Arm D Total Body Irradiation HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Bone marrow infusion HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Donor mesenchymal stem cell infusions HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Alone Arm F Total Body Irradiation 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 HCT Alone Arm F Bone marrow infusion 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 HCT Alone Arm F Donor mesenchymal stem cell infusions 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 HCT plus MSC Arm G Cyclophosphamide 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 HCT plus MSC Arm G Fludarabine 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 HCT plus MSC Arm G Total Body Irradiation 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 HCT plus MSC Arm G Bone marrow infusion 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 HCT plus MSC Arm G Tacrolimus 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 HCT plus MSC Arm G Mycophenolate Mofetil 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 HCT plus MSC Arm G Donor mesenchymal stem cell infusions 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 HCT plus MSC Arm G Busulfan 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 RDEB: HCT plus MSC Arm B Tacrolimus 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). RDEB: HCT plus MSC Arm B Mycophenolate Mofetil 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). JEB: HCT plus MSC Arm B Fludarabine 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). JEB: HCT plus MSC Arm B Cyclophosphamide 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). JEB: HCT plus MSC Arm B Thymoglobulin 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). RDEB: HCT Plus MSC Arm E Thymoglobulin 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). JEB: HCT plus MSC Arm B Tacrolimus 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). JEB: HCT plus MSC Arm B Mycophenolate Mofetil 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). RDEB: HCT Plus MSC Arm E Cyclophosphamide 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). RDEB: HCT Plus MSC Arm E Fludarabine 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). RDEB: HCT Plus MSC Arm E Mycophenolate Mofetil 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). RDEB: HCT Plus MSC Arm E Tacrolimus 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). HCT with 300 cGy of TBI Arm A Thymoglobulin Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. HCT with 300 cGy of TBI Arm A Cyclophosphamide Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. HCT with 300 cGy of TBI Arm A Fludarabine Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. HCT with 300 cGy of TBI Arm A Tacrolimus Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. Re-Transplant Arm C Thymoglobulin Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. Re-Transplant Arm C Cyclophosphamide Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. HCT with 300 cGy of TBI Arm A Mycophenolate Mofetil Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. Re-Transplant Arm C Fludarabine Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. Re-Transplant Arm C Tacrolimus Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. Re-Transplant Arm C Mycophenolate Mofetil Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. HCT Arm D Thymoglobulin HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Cyclophosphamide HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Fludarabine HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Tacrolimus HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Arm D Mycophenolate Mofetil HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). HCT Alone Arm F Thymoglobulin 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 HCT Alone Arm F Cyclophosphamide 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 HCT Alone Arm F Fludarabine 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 HCT Alone Arm F Mycophenolate Mofetil 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 HCT Alone Arm F Tacrolimus 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 HCT plus MSC Arm G Thymoglobulin 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 HCT Alone Arm F Busulfan 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
- Primary Outcome Measures
Name Time Method Event-free Survival 1 year post-transplant An event defined as death or a 50% increase in a patient's IScoreEB from baseline
- Secondary Outcome Measures
Name Time Method Change of a Patient's iscorEB 1 year post-transplant iscorEB surveys are a validated, standard of care tool used to assess disease status in patients with Epidermolysis Bullosa. Measure changes in quality of life (QOL) through pain, itching, and general QOL IScorEB questionnaire. Scores can range from 16 to 112. The QOLS scores are summed so that a higher score indicates higher quality of life.
Transplant-related Mortality 180 days post-transplant Cumulative incidence will be used to estimate the probability of relapse treating non-relapse death as a competing risk and transplant-related mortality conversely treating relapse as a competing risk.
Average Change in Quality of Life 2 years post-transplant Measured by the Lansky or Karnofsky score (10-100). The Karnofsky Performance Scale is an assessment tool intended to gauge a patient's functional status and ability to carry out activities of daily living. Higher scores indicate a better outcome. Midpoint of change in scores used to indicate median.
Lymphoid Chimerism Day 28, 60, 100, 180, and year 1 and 2 post-transplant Median hematopoietic cells that are of donor origin per participant.
Myeloid Chimerism Day 28, 60, 100, 180, and year 1 and 2 post-transplant Median hematopoietic cells that are of donor origin per participant.
Average Change of a Patient's iscorEB 2 year post-transplant iscorEB surveys are a validated, standard of care tool used to assess disease status in patients with Epidermolysis Bullosa. Measure percent of changes in quality of life (QOL) through pain, itching, and general QOL IScorEB questionnaire. Scores can range from 16 to 112. The QOLS scores are summed so that a higher score indicates higher quality of life.
Trial Locations
- Locations (1)
University of Minnesota Masonic Cancer Center and Medical Center
🇺🇸Minneapolis, Minnesota, United States