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| ID | Type | Description | Link |
|---|---|---|---|
| P01CA039542 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious and potentially fatal complication. The researchers have developed a blood test to identify patients most at risk for developing severe GVHD. Patients who consent to this study will have their blood tested up to two times after BMT to determine if they are at high risk for severe GVHD. The tests will be performed one week and two weeks after BMT. Patients who are high risk will be treated with a drug called alpha-1-antitrypsin (AAT) to see if it prevents the development of severe GVHD. Patients will receive 16 doses of AAT through a catheter placed into a blood vessel over eight weeks. AAT will be given either in the hospital or the outpatient clinic two times per week. Patients will be followed for the development of severe GVHD for up to four months from the BMT and will continue to be followed at routine clinic visits for up to one year after BMT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| alpha-1-antitrypsin (AAT) | Experimental | 16 doses of AAT through a catheter placed into a blood vessel over eight weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alpha 1-Antitrypsin | Drug | AAT will be given either in the hospital or the outpatient clinic two times per week. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of High Risk Patients Who Develop Steroid Refractory GVHD | Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) . Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment.
| Day 100 post HCT. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Alive at 6 Months and 1 Year | Overall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year | 6 months and 1 year |
| Number of Participants With Non-relapse Mortality (NRM) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Levine, MD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Duarte | California | 91010 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33351103 | Result | Gergoudis SC, DeFilipp Z, Ozbek U, Sandhu KS, Etra AM, Choe HK, Kitko CL, Ayuk F, Aziz M, Baez J, Ben-David K, Bunworasate U, Gandhi I, Hexner EO, Hogan WJ, Holler E, Kasikis S, Kowalyk SM, Lin JY, Merli P, Morales G, Nakamura R, Reshef R, Rosler W, Srinagesh H, Young R, Chen YB, Ferrara JLM, Levine JE. Biomarker-guided preemption of steroid-refractory graft-versus-host disease with alpha-1-antitrypsin. Blood Adv. 2020 Dec 22;4(24):6098-6105. doi: 10.1182/bloodadvances.2020003336. |
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Subjects were recruited and enrolled between August 2018 and July 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alpha-1-antitrypsin (AAT) | AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Alpha-1-antitrypsin (AAT) | AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Number of High Risk Patients Who Develop Steroid Refractory GVHD | Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) . Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment.
| Posted | Count of Participants | Participants | Day 100 post HCT. |
|
up to 1 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 | Alpha-1-antitrypsin (AAT) | AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Engraftment Syndrome | General disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John Levine | Icahn School of Medicine at Mount Sinai | 212-241-6021 | john.levine@mssm.edu |
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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 | Nov 15, 2019 | Mar 25, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000515 | alpha 1-Antitrypsin |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D015843 | Serpins |
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Open label single arm
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Number of participants with NRM - deaths which could not be attributed to disease relapse or progression. Non-relapse mortality defined as death without prior relapse.
| 6 months and 1 year |
| Number of Participants With Relapse | Number of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant. | 1 year |
| Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD | Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment. GVHD grades II-IV are defined as
| 100 days |
| Number of Participants Achieving Overall Response | For patients who develop GVHD prior to day 100 post-HCT, the number of participants achieving overall response. The overall response rate = complete remission and partial remission (CR + PR) 28 days after initiation of systemic steroid treatment. | Day 28 |
| Number of Participants With Severe GI GVHD Stage 3 or 4 | Number of participants with severe GI GVHD stage 3 or 4. GI GVHD stage 3 or 4 is defined as diarrhea >1000 ml/day OR severe abdominal pain requiring treatment OR blood present in the diarrhea. | By day 100 post-HCT |
| Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment | Number of participants with chronic GVHD requiring systemic steroid treatment. Chronic GVHD Requiring Systemic Steroid Treatment: defined as the development of symptoms of chronic GVHD according to NIH Consensus Criteria that require treatment with oral or intravenous corticosteroids. | 1 year |
| Number of Participants With Serious Infections | Number of participants with serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network). Serious Infection: Defined as bacterial, fungal, viral or parasitic infections that required oral or intravenous treatments such as antibiotics. | 1 year |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Ohio State University | Columbus | Ohio | 43210 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Diagnosis | Count of Participants | Participants |
|
| Donor | Count of Participants | Participants |
|
| GVHD Prophylaxis | Chronic Graft Vs. Host Disease | Count of Participants | Participants |
|
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|
| Secondary | Number of Participants Alive at 6 Months and 1 Year | Overall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year | Posted | Count of Participants | Participants | 6 months and 1 year |
|
|
|
| Secondary | Number of Participants With Non-relapse Mortality (NRM) | Number of participants with NRM - deaths which could not be attributed to disease relapse or progression. Non-relapse mortality defined as death without prior relapse. | Posted | Count of Participants | Participants | 6 months and 1 year |
|
|
|
| Secondary | Number of Participants With Relapse | Number of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD | Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment. GVHD grades II-IV are defined as
| Posted | Count of Participants | Participants | 100 days |
|
|
|
| Secondary | Number of Participants Achieving Overall Response | For patients who develop GVHD prior to day 100 post-HCT, the number of participants achieving overall response. The overall response rate = complete remission and partial remission (CR + PR) 28 days after initiation of systemic steroid treatment. | This is the number of patients who developed GVHD and were systemically treated (not all patients on study developed GVHD and of those that did develop GVHD, not all received systemic treatment). | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| Secondary | Number of Participants With Severe GI GVHD Stage 3 or 4 | Number of participants with severe GI GVHD stage 3 or 4. GI GVHD stage 3 or 4 is defined as diarrhea >1000 ml/day OR severe abdominal pain requiring treatment OR blood present in the diarrhea. | Posted | Count of Participants | Participants | By day 100 post-HCT |
|
|
|
| Secondary | Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment | Number of participants with chronic GVHD requiring systemic steroid treatment. Chronic GVHD Requiring Systemic Steroid Treatment: defined as the development of symptoms of chronic GVHD according to NIH Consensus Criteria that require treatment with oral or intravenous corticosteroids. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| Secondary | Number of Participants With Serious Infections | Number of participants with serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network). Serious Infection: Defined as bacterial, fungal, viral or parasitic infections that required oral or intravenous treatments such as antibiotics. | Posted | Count of Participants | Participants | 1 year |
|
|
|
| 8 |
| 30 |
| 14 |
| 30 |
| 9 |
| 30 |
| GVHD | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Graft Versus Host Disease |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Line Infection: Gram negative Bacilli-Citrobacter | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Fungal Infection: Pneumocystis carinii pneumonia (PCP) | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Pneumocystis carinii pneumonia |
|
| Fungal Infection: Aspergillus | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Bronchopulmonary hemorrhage (DAH) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Adult Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Relapse | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Thrombotic microangiopathy | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Maculopapular rash with engraftment syndrome | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Oral mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Maculopapular Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Klebsiella | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Infusion Reaction | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Generalized muscle weakness | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Low platelets | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000209 | Acute-Phase Proteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000510 | Alpha-Globulins |
| D012712 | Serum Globulins |
| D005916 | Globulins |