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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00031590 | Other Identifier | JHMIRB |
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Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.
This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.
You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.
A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.
People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bone marrow transplant | Experimental | Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bone marrow transplant | Procedure | Day 0 |
| |
| Thymoglobulin |
| Measure | Description | Time Frame |
|---|---|---|
| Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe? | Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180). | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients That Have Survived at One Year | 1 year | |
| Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant | Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with >5% donor chimerism around day 60 will be considered as having engrafted. |
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Inclusion Criteria:
Patients with relapsed or refractory SAA or very SAA defined:
Bone marrow (< 25% cellular)
Peripheral cytopenias (at least 2 of 3)
Very severe: as above, but ANC < 200
Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or PNH)
Failed at least one course of immunosuppressive therapy (if presumed acquired disease). Patients with inherited disease will be characterized as refractory and do not require immunosuppressive first.
Age 0- upper age limit as determined by current institutional standards
Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.
Patients must be geographically accessible and willing to participate in all stages of treatment.
Adequate end-organ function as measured by:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy DeZern, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21287 | United States | ||
| Medical College of Wisconsin/Children's Hospital of Wisconsin |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32343796 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bone Marrow Transplant | Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 Bone marrow transplant: Day 0 Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7 Fludarabine: 30 mg/M2 IV on days -6 to -2 Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4 TBI: 200 cGy on day -1 Mesna: 40 mg/kg IV on days 3, 4 Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35 |
| 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 11, 2021 |
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| Drug |
0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7 |
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| Fludarabine | Drug | 30 mg/M2 IV on days -6 to -2 |
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| Cyclophosphamide | Drug | 14.5 mg/kg IV on days -6, -5, 3, 4 |
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| TBI | Radiation | 200 cGy on day -1 |
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| Mesna | Drug | 40 mg/kg IV on days 3, 4 |
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| Tacrolimus | Drug | For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present |
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| Mycophenolic acid mofetil | Drug | 15 mg/kg PO/IV TID beginning on day 5 through day 35 |
|
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| 60 days |
| Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant | 1 year |
| Number of Participants With Major Toxicities Related to Transplant | 1 year |
| Number of Patients That Expired Due to Transplant Related Mortality | 1 year |
| Number of Patients With Primary or Secondary Graft Failure Following Transplant | Graft failure: < 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements. Primary graft failure: < 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of > 5% donor chimerism, followed by sustained <5% donor chimerism in blood and/or bone marrow. | 1 year |
| Number of Participants With Grade II-IV or Grade III-IV Acute GVHD | Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement | 1 year |
| Participants With Chronic GVHD at One Year | 1 year |
| Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant | CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC > 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential. | 1 year |
| Participants That Were GVHD Free, Relapse Free Survival (GRFS) | 1 year |
| Milwaukee |
| Wisconsin |
| 53226 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Bone Marrow Transplant | Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 Bone marrow transplant: Day 0 Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7 Fludarabine: 30 mg/M2 IV on days -6 to -2 Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4 TBI: 200 cGy on day -1 Mesna: 40 mg/kg IV on days 3, 4 Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35 |
| 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 |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| 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 | Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe? | Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180). | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Number of Patients That Have Survived at One Year | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant | Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with >5% donor chimerism around day 60 will be considered as having engrafted. | Posted | Count of Participants | Participants | 60 days |
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| Secondary | Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Number of Participants With Major Toxicities Related to Transplant | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Number of Patients That Expired Due to Transplant Related Mortality | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Number of Patients With Primary or Secondary Graft Failure Following Transplant | Graft failure: < 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements. Primary graft failure: < 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of > 5% donor chimerism, followed by sustained <5% donor chimerism in blood and/or bone marrow. | Posted | Count of Participants | Participants | 1 year |
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| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Grade II-IV or Grade III-IV Acute GVHD | Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement | Posted | Count of Participants | Participants | 1 year |
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| ||||||||||||||||||||||||||||
| Secondary | Participants With Chronic GVHD at One Year | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant | CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC > 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential. | Posted | Median | Full Range | days | 1 year |
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| Secondary | Participants That Were GVHD Free, Relapse Free Survival (GRFS) | Posted | Count of Participants | Participants | 1 year |
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Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
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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 | Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 Bone marrow transplant: Day 0 Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7 Fludarabine: 30 mg/M2 IV on days -6 to -2 Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4 TBI: 200 cGy on day -1 Mesna: 40 mg/kg IV on days 3, 4 Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35 | 0 | 18 | 7 | 18 | 0 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Respiratory Distress Syndrom | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Acute Hypoxic Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Intracranial Hemorrhage | Vascular disorders | Systematic Assessment |
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| Retroperitoneal Hemorrhage | Vascular disorders | Systematic Assessment |
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| Hemorrhagic Shock | Vascular disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Persistent Fevers | Infections and infestations | Systematic Assessment |
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| dysuria/hematuria | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amy DeZern | Johns Hopkins University | 4105027208 | Adezern1@jhmi.edu |
| Dec 13, 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 |
|---|---|
| D016026 | Bone Marrow Transplantation |
| C512542 | thymoglobulin |
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| D015080 | Mesna |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D016378 | Tissue Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| 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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