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| ID | Type | Description | Link |
|---|---|---|---|
| 1U54HL112303-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma exchange often are helped by later treatment with rituximab. The purpose of this study is to see whether combining low doses of rituximab with plasma exchange will help patients get better sooner and reduce the chance of getting TTP again.
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for the treatment of thrombotic thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab may decrease the incidence of a composite primary endpoint (exacerbations or refractory disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess the utility of ADAMST13 as a biomarker for response to therapy and prognosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| low dose rituximab | Experimental | this is a single-arm trial |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rituximab | Biological | rituximab intravenously 100 mg every week for four doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP | Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60. | 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Durable Treatment Response | Treatment Response is 2 consecutive days with platelet count ≥150, 000/µL Durable Treatment Response is a Treatment Response that persists for ≥30 days after discontinuation of plasma exchange and includes those with exacerbations | 60 days |
| Number of Days to Durable Treatment Response |
Not provided
Inclusion Criteria:
Age 18 or greater
Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
Subjects who will receive treatment for TTP with plasma exchange
Subjects who have not started the 5th plasma exchange
Plasma ADAMTS13 activity <10%
Exclusion Criteria:
Treatment for TTP within the past 2 months
Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli O157:H7 or related organism
Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
Microangiopathic hemolytic anemia due to a mechanical heart valve
Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
Organ or stem cell transplant
Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
Disseminated intravascular coagulation as defined by:
a. INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen <100 mg/dl
Pregnancy
Known congenital TTP.
Rituximab within the previous year.
HIV history or positive serology
History of hepatitis B or positive serology for HBsAg or Anti-HBc
Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation
Hypersensitivities or allergies to murine and/or humanized antibodies
Current participation in trials of investigational therapies or devices, other than central catheters
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| Name | Affiliation | Role |
|---|---|---|
| Elaine M Majerus, MD, PhD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States | ||
| Beth Israel Deaconess Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21926591 | Background | Froissart A, Buffet M, Veyradier A, Poullin P, Provot F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. doi: 10.1097/CCM.0b013e31822e9d66. | |
| 20058208 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Rituximab | this is a single-arm trial rituximab: rituximab intravenously 100 mg every week for four doses |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants consenting
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose Rituximab | this is a single-arm trial rituximab: rituximab intravenously 100 mg every week for four doses |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP | Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60. | Completed adjuvant riituximab therapy | Posted | Count of Participants | Participants | 60 days |
|
|
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 | Low Dose Rituximab | this is a single-arm trial rituximab: rituximab intravenously 100 mg every week for four doses |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| multi-system organ failure | General disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| rhinorrhea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elaine Majerus | Washington University | 314-362-8866 | emajerus@wustl.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 | Oct 18, 2018 | Feb 8, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011697 | Purpura, Thrombotic Thrombocytopenic |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Median time to treatment response |
| 60 days |
| Incidence of Relapse | Relapse is recurring TTP >30 days after Treatment Response | Between 30 days and 2 years |
| Months to Relapse | Mean months to relapse | 2 years |
| Incidence of Death | Incidence of death will be assessed at 4 weeks, 1 year and 2 years | 2 years |
| Treatment-related Adverse Events | Incidence, type and severity of treatment-related adverse events will be assessed. Patient reports, lab values, and physical exam were used to identify treatment-related adverse events. | 2 years |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Washington University | St Louis | Missouri | 63110 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Result |
| Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z. |
| 23279219 | Result | Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013 Mar;11(3):481-90. doi: 10.1111/jth.12114. |
| 15389904 | Result | Ahmad A, Aggarwal A, Sharma D, Dave HP, Kinsella V, Rick ME, Schechter GP. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol. 2004 Oct;77(2):171-6. doi: 10.1002/ajh.20166. |
| 12353309 | Result | Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Sohngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. doi: 10.1002/ajh.10204. |
| Participants |
| No |
|
| 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 |
|
| Participants |
|
|
| Secondary | Incidence of Durable Treatment Response | Treatment Response is 2 consecutive days with platelet count ≥150, 000/µL Durable Treatment Response is a Treatment Response that persists for ≥30 days after discontinuation of plasma exchange and includes those with exacerbations | Completed adjuvant rituximab therapy | Posted | Count of Participants | Participants | 60 days |
|
|
|
| Secondary | Number of Days to Durable Treatment Response | Median time to treatment response | Completed adjuvant rituximab therapy | Posted | Median | Full Range | days | 60 days |
|
|
|
| Secondary | Incidence of Relapse | Relapse is recurring TTP >30 days after Treatment Response | Posted | Count of Participants | Participants | Between 30 days and 2 years |
|
|
|
| Secondary | Months to Relapse | Mean months to relapse | Completed adjuvant rituximab | Posted | Mean | Full Range | months | 2 years |
|
|
|
| Secondary | Incidence of Death | Incidence of death will be assessed at 4 weeks, 1 year and 2 years | Completed adjuvant rituximab | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Treatment-related Adverse Events | Incidence, type and severity of treatment-related adverse events will be assessed. Patient reports, lab values, and physical exam were used to identify treatment-related adverse events. | Completed adjuvant rituximab therapy | Posted | Number | treatment-related adverse events | 2 years |
|
|
|
| 1 |
| 17 |
| 10 |
| 17 |
| 17 |
| 19 |
| Lower Gastrointestinal Bleed | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| heart failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| sepsis, gram-negative bacterial infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| fever, central line complication, bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| thrombocytopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| shock, acute respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Atrial Fibrillation with Rapid Ventricular Response | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| neck pain, abdominal distention | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| cellulitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| chest pain, palpitations, shortness of breath | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Relapsed Thrombotic Thrombocytopenia Purpura | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyper-somnolence with hypoxia and hypotension | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pancreatitis (presenting symptom abdominal pain) | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| decreased appetite | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| thrombocytopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| cervical lymphadenopathy | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| left hand numbness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| ulcer to right nostril | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| sleep disturbances/insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| acne | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| weight gain | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| swelling | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| delirium | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| elevated creatinine | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| pruritis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| hives | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | occurred during plasma pheresis |
|
| fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| heart palpitations | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| pain - lips | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| shortness of breath | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte decrease | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Edema to face | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Elevated Total Bilirubin | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| flu-like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| hemorrhoidal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| gingival bleeding | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| hypernatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| double vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| floaters | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| ALT Elevation | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| AST elevation | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| GI Disorder | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| anaphylaxis | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| muscle pain/myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| gastro-esophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| paresthesia - hands | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| menopause | Social circumstances | CTCAE (4.0) | Systematic Assessment |
|
| uterine infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| vaginal discharge | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| endometritis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| hallucinations | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| hot flashes | Social circumstances | CTCAE (4.0) | Systematic Assessment |
|
| night sweats | Social circumstances | CTCAE (4.0) | Systematic Assessment |
|
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| D006425 |
| Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D019851 | Thrombophilia |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |