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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00107139 | Other Identifier | JHMIRB |
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Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.
This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bone marrow transplant | Experimental | Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thymoglobulin | Drug | Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival and Engraftment at One Year | Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT). | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at One Year | Number of participants alive at one year after BMT. | 1 year |
| Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts |
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Inclusion Criteria:
Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)
One of the following available donors:
Recipient and/or legal guardian must sign protocol informed consent
Donor must be willing to donate bone marrow
Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.
Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age
For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight
For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.
For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%
For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air
Karnofsky/Lansky status (depending on age) >= 70%
Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy E DeZern, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37084383 | Derived | DeZern AE, Zahurak M, Symons HJ, Cooke KR, Huff CA, Jain T, Swinnen LJ, Imus PH, Wagner-Johnston ND, Ambinder RF, Levis M, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023 Jun 22;141(25):3031-3038. doi: 10.1182/blood.2023020435. | |
| 32343796 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bone Marrow Transplant | Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as graft-versus-host disease (GVHD) prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) |
| 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 | Aug 24, 2020 |
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| Fludarabine | Drug | Days -6 through -2: 30 mg/m^2 IV daily |
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| Cyclophosphamide | Drug | Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily |
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| Total body irradiation | Radiation | Day -1: 200 centigray (cGy) in a single fraction |
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| Tacrolimus | Drug | Start on Day 5 through Day 365 |
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| Mycophenolate mofetil | Drug | Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) |
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Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC).
| 1 year |
| Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts | Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year. | 1 year |
| Number of Participants Who Experience Primary Graft Failure | Number of participants who experience primary graft failure by one year after BMT. | 1 year |
| Number of Participants Who Experience Secondary Graft Failure | Number of participants who experience secondary graft failure by one year after BMT. | 1 year |
| Number of Participants Who Experience Grades II-IV Acute GVHD | Number of participants who experience grade II, III, or IV acute GVHD by Day 100. | Day 100 |
| Number of Participants Who Experience Grades III-IV Acute GVHD | Number of participants who experience grade III or IV acute GVHD by Day 100. | Day 100 |
| Number of Participants Who Experience Chronic GVHD | Number of participants who experience chronic GVHD by two years after BMT. | 2 years |
| Number of Participants With Full Donor Chimerism | Number of participants with full donor chimerism at Day 60. | Day 60 |
| GVHD-free Relapse-free Survival (GRFS) | Number of participants alive, without relapse, and without GVHD at 1 year. | 1 year |
| Transplant-related Mortality | Number of participants deceased for reasons related to BMT at 1 year. | 1 year |
| DeZern AE, Zahurak ML, Symons HJ, Cooke KR, Rosner GL, Gladstone DE, Huff CA, Swinnen LJ, Imus P, Borrello I, Wagner-Johnston N, Ambinder RF, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide. Blood Adv. 2020 Apr 28;4(8):1770-1779. doi: 10.1182/bloodadvances.2020001729. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Bone Marrow Transplant | Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) |
| 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 |
| |||||||||||||||||||||||
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | 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 | Overall Survival and Engraftment at One Year | Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT). | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Overall Survival at One Year | Number of participants alive at one year after BMT. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts | Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC). | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts | Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year. | Posted | Count of Participants | Participants | 1 year |
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| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Primary Graft Failure | Number of participants who experience primary graft failure by one year after BMT. | Posted | Count of Participants | Participants | 1 year |
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| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Secondary Graft Failure | Number of participants who experience secondary graft failure by one year after BMT. | Posted | Count of Participants | Participants | 1 year |
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| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Grades II-IV Acute GVHD | Number of participants who experience grade II, III, or IV acute GVHD by Day 100. | Posted | Count of Participants | Participants | Day 100 |
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| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Grades III-IV Acute GVHD | Number of participants who experience grade III or IV acute GVHD by Day 100. | Posted | Count of Participants | Participants | Day 100 |
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| Secondary | Number of Participants Who Experience Chronic GVHD | Number of participants who experience chronic GVHD by two years after BMT. | Posted | Count of Participants | Participants | 2 years |
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| Secondary | Number of Participants With Full Donor Chimerism | Number of participants with full donor chimerism at Day 60. | Posted | Count of Participants | Participants | Day 60 |
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| Secondary | GVHD-free Relapse-free Survival (GRFS) | Number of participants alive, without relapse, and without GVHD at 1 year. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Transplant-related Mortality | Number of participants deceased for reasons related to BMT at 1 year. | Posted | Count of Participants | Participants | 1 year |
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Adverse events were monitored and collected from time of consent up to one year.
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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 | Bone Marrow Transplant | Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) | 2 | 21 | 2 | 21 | 0 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gram negative rods Bacteremia | Infections and infestations | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Amy DeZern | Johns Hopkins University | 410-502-7208 | adezerb1@jhmi.edu |
| Apr 26, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| D000080983 | Bone Marrow Failure Disorders |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
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| ID | Term |
|---|---|
| C512542 | thymoglobulin |
| D000961 | Antilymphocyte Serum |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003520 | Cyclophosphamide |
| D014916 | Whole-Body Irradiation |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| 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 |
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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 |
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| Other |
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