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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RDEB: HCT plus MSC Arm B | Experimental | 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). |
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| JEB: HCT plus MSC Arm B | Experimental | 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). |
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| RDEB: HCT Plus MSC Arm E | Experimental | 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thymoglobulin | Drug | 0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2 |
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| Measure | Description | Time Frame |
|---|---|---|
| Event-free Survival | An event defined as death or a 50% increase in a patient's IScoreEB from baseline | 1 year post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Change of a Patient's iscorEB | 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. | 1 year post-transplant |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Jakub Tolar, MD, PhD | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota Masonic Cancer Center and Medical Center | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30843184 | Derived | Ebens CL, McGrath JA, Tamai K, Hovnanian A, Wagner JE, Riddle MJ, Keene DR, DeFor TE, Tryon R, Chen M, Woodley DT, Hook K, Tolar J. Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts. Br J Dermatol. 2019 Dec;181(6):1238-1246. doi: 10.1111/bjd.17858. Epub 2019 Jun 28. |
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The JEB subject (n=1) was enrolled on Arm B, receiving the same therapy as the RDEB subjects, but pulled out and reported separately due to the very different baseline disease course.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 5, 2019 |
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| HCT with 300 cGy of TBI Arm A | Experimental | Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions. |
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| Re-Transplant Arm C | Experimental | Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. |
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| HCT Arm D | Experimental | HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). |
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| HCT Alone Arm F | Experimental | 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 |
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| HCT plus MSC Arm G | Experimental | 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 |
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| Cyclophosphamide | Drug | 14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3 |
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| Fludarabine | Drug | 30 mg/m2 IV over 60 minutes days -6 through day -2 |
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| Total Body Irradiation | Radiation | See arm description for dosing. |
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| Bone marrow infusion | Procedure | Bone marrow infusion on Day 0 |
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| Tacrolimus | Drug | Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors). When used in non-MSD recipients, tapered over 6-8 weeks starting at day +100. |
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| Mycophenolate Mofetil | Drug | 15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35 |
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| Donor mesenchymal stem cell infusions | Biological | Day 60, 100 and 180 (collected during donor BM harvest for graft) |
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| Busulfan | Drug | busulfan IV over 3 hours on days -3 and -2 for HLA-mismatched BM recipients only (Arms F and G) |
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| Transplant-related Mortality | 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. | 180 days post-transplant |
| Average Change in Quality of Life | Measured by the Lansky or Karnofsky score (10-100). Higher scores indicate a better outcome. Midpoint of change in scores used to indicate median. | 1 year post-transplant |
| Average Change in Quality of Life | 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. | 2 years post-transplant |
| Lymphoid Chimerism | Median hematopoietic cells that are of donor origin per participant. | Day 28, 60, 100, 180, and year 1 and 2 post-transplant |
| Myeloid Chimerism | Median hematopoietic cells that are of donor origin per participant. | Day 28, 60, 100, 180, and year 1 and 2 post-transplant |
| Average Change of a Patient's iscorEB | 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. | 2 year post-transplant |
| FG001 | 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). |
| FG002 | 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). |
| FG003 | 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. |
| FG004 | Re-Transplant Arm C | Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI. |
| FG005 | HCT Arm D | HLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total). |
| FG006 | 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 |
| FG007 | 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 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | RDEB: HCT Plus MSC 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). |
| BG001 | RDEB: HCT Plus MSC 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). |
| BG002 | 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). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Event-free Survival | An event defined as death or a 50% increase in a patient's IScoreEB from baseline | Posted | Number | Count of Participants | 1 year post-transplant |
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| Secondary | Change of a Patient's iscorEB | 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. | Posted | Mean | Full Range | units on a scale | 1 year post-transplant |
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| Secondary | Transplant-related Mortality | 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. | Posted | Number | Participants | 180 days post-transplant |
| |||||||||||||||||||||||||||||||||||
| Secondary | Average Change in Quality of Life | Measured by the Lansky or Karnofsky score (10-100). Higher scores indicate a better outcome. Midpoint of change in scores used to indicate median. | Posted | Median | Inter-Quartile Range | Change in score | 1 year post-transplant |
| ||||||||||||||||||||||||||||||||||
| Secondary | Average Change in Quality of Life | 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. | Participant in "JEB: HCT plus MSC Arm B" deceased at 2 year post-transplant timepoint. | Posted | Median | Inter-Quartile Range | Change in score | 2 years post-transplant |
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| Secondary | Lymphoid Chimerism | Median hematopoietic cells that are of donor origin per participant. | Participants in "RDEB: HCT plus MSC" arm unable to be analyzed due to missed visits. | Posted | Median | Full Range | Percentage of donor derived cells | Day 28, 60, 100, 180, and year 1 and 2 post-transplant |
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| Secondary | Myeloid Chimerism | Median hematopoietic cells that are of donor origin per participant. | Participants in "RDEB: HCT plus MSC" arm unable to be analyzed due to missed visits. | Posted | Median | Full Range | Percentage of donor derived cells | Day 28, 60, 100, 180, and year 1 and 2 post-transplant |
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| Secondary | Average Change of a Patient's iscorEB | 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. | Participant in "JEB: HCT plus MSC Arm B" deceased at 2 year post-transplant timepoint. | Posted | Mean | Inter-Quartile Range | units on a scale | 2 year post-transplant |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 0 | 7 | 2 | 7 | 2 | 7 |
| EG001 | 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). | 1 | 9 | 1 | 9 | 1 | 9 |
| EG002 | 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). | 1 | 1 | 0 | 1 | 1 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Other, specify - Veno-occlusive disease | Hepatobiliary disorders | Systematic Assessment |
| ||
| Reversible posterior leukoencephalopathy syndrome | Investigations | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment |
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| Sepsis | Infections and infestations | Systematic Assessment |
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| Nervous system disorders - Other, specify | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christen Ebens | University of Minnesota, Masonic Cancer Center | (612) 626-5654 | ebens012@umn.edu |
| Dec 19, 2023 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 15, 2019 | Dec 19, 2023 | ICF_001.pdf |
| ID | Term |
|---|---|
| D004820 | Epidermolysis Bullosa |
| ID | Term |
|---|---|
| D012868 | Skin Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012872 | Skin Diseases, Vesiculobullous |
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| ID | Term |
|---|---|
| C512542 | thymoglobulin |
| D000961 | Antilymphocyte Serum |
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D014916 | Whole-Body Irradiation |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| D002066 | Busulfan |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D018942 | Macrolides |
| D007783 | Lactones |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|
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).
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| 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). |
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| OG002 |
| 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). |
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