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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00082453 | Other Identifier | Johns Hopkins IRB |
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Study was unable to accrue subjects
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| Name | Class |
|---|---|
| Maryland Stem Cell Research Fund | UNKNOWN |
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The main goal of the study is to determine if bone marrow transplant (BMT) from a less specific pool of donors in combination with high dose cyclophosphamide can induce remission of refractory systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a devastating systemic autoimmune disease that predominantly affects young women, is more common in African-Americans than in whites, and results in poor quality of life. Lupus has no cure, and up to 90% of patients require corticosteroids for disease control. More than half of patients with lupus have permanent organ damage, much of which is either directly due to or increased by corticosteroids. To satisfactorily manage moderate-to-severe SLE, the investigators need effective treatments that will allow corticosteroid-sparing.
High-dose chemotherapy followed by autologous BMT or peripheral blood progenitor transplantation (PBSCT) has been proposed as a novel approach to treat severe autoimmune diseases. Allogeneic BMT is not currently utilized for the routine treatment of SLE because of the significant morbidity (GVHD) and mortality associated with the procedure.
The investigators have recently developed an approach to BMT using post-transplant cyclophosphamide that allows us to safely perform allogeneic BMT from matched, mismatched, unrelated or haploidentical donors. Transplant-related mortality, graft-failure and risk of GVHD have been very low with this approach. Furthermore, this approach allows us to greatly expand the donor pool since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases.
This trial will employ a fludarabine + cyclophosphamide conditioning along with posttransplantation cyclophosphamide on for patients with refractory SLE. The purpose of this trial is to improve the salvage rate for patients with refractory SLE through a reformatting of the immune system.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nonmyeloablative Conditioning and BMT | Experimental | Nonmyeloablative conditioning with rabbit antithymocyte globulin, cyclophosphamide, fludarabine, and total body irradiation. Allogeneic bone marrow transplant on Day 0. Graft versus host disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and tacrolimus. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | 14.5 mg/kg/day on Days -6 and -5. 50 mg/kg/day on Days 3 and 4. |
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| Measure | Description | Time Frame |
|---|---|---|
| The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching | Number of participants who were alive at 1 year after transplant and who had not suffered graft rejection, acute or chronic GVHD, or Grade 3 or higher (CTCAE V4.0) adverse events. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| RIFLE Score | Change in Responder Index for Systemic Lupus Erythematosis (RIFLE) assessment. This is a qualitative assessment of organ function. The 12 month response will be assessed as: complete= complete or partial resolution in more than one organ, partial= complete or partial resolution in at least one organ, the same= no change or no worsening in any organ, worse= worsening in any organ | 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Javier Bolaños-Meade, MD | The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21205 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nonmyeloablative Conditioning and BMT | Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant |
| 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 | Jun 7, 2016 |
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| Fludarabine | Drug | 30 mg/m^2/day on Days -6 through -2. |
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| Tacrolimus | Drug | Starting on Day 5. Dose will be adjusted according to blood levels. |
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| Mycophenolate Mofetil | Drug | 15 mg/kg three times per day from Day 5 to Day 35. |
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| Rabbit antithymocyte globulin | Drug | 0.5 mg/kg on Day -9. 2 mg/kg/day on Days -8 and -7. |
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| Total body irradiation | Radiation | 200 centigray on Day -1. |
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| Allogeneic bone marrow transplant | Biological | Infusion on Day 0. |
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| Survival | Number of patients alive and alive without relapse, respectively. | 1 year |
| Graft Failure | Number of participants with primary and/or secondary graft failure. | 60 days |
| Acute Graft Versus Host Disease (GVHD) | Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). | Up to 2 years |
| Chronic Graft Versus Host Disease (GVHD) | Percentage of participants who developed chronic GVHD as defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Mild chronic GVHD involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites). Moderate chronic GVHD involves 1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR 2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site). | Up to 2 years |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Nonmyeloablative Conditioning and BMT | Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant |
| Units | Counts |
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| 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 |
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| 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 | The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching | Number of participants who were alive at 1 year after transplant and who had not suffered graft rejection, acute or chronic GVHD, or Grade 3 or higher (CTCAE V4.0) adverse events. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | RIFLE Score | Change in Responder Index for Systemic Lupus Erythematosis (RIFLE) assessment. This is a qualitative assessment of organ function. The 12 month response will be assessed as: complete= complete or partial resolution in more than one organ, partial= complete or partial resolution in at least one organ, the same= no change or no worsening in any organ, worse= worsening in any organ | The only enrolled participant on this study was never assessed for a follow-up RIFLE scale, so no data was collected for this outcome measure. | Posted | 1 year |
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| Secondary | Survival | Number of patients alive and alive without relapse, respectively. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Graft Failure | Number of participants with primary and/or secondary graft failure. | Posted | Count of Participants | Participants | 60 days |
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| Secondary | Acute Graft Versus Host Disease (GVHD) | Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). | Posted | Count of Participants | Participants | Up to 2 years |
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| Secondary | Chronic Graft Versus Host Disease (GVHD) | Percentage of participants who developed chronic GVHD as defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Mild chronic GVHD involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites). Moderate chronic GVHD involves 1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR 2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site). | Posted | Count of Participants | Participants | Up to 2 years |
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Adverse events were assessed weekly through at least Day 60.
Reportable serious adverse events per protocol include: any mortality within the first 100 days after bone marrow transplant (BMT), any graft failures (defined as <5% donor chimerism) associated with failure of neutrophil recovery to >500/mm³ by day ~60 after transplantation, and all unexpected events as deemed significant by the PIs. Other events were neither tracked nor reported for this study.
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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 | Nonmyeloablative Conditioning and BMT | Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant | 0 | 1 | 0 | 1 | 0 | 1 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Javier Bolaños Meade, MD | The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | 410-614-6398 | fbolano2@jhmi.edu |
| Sep 6, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| C512542 | thymoglobulin |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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| Unknown or Not Reported |
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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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| Units | Counts |
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| Participants |
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