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Single center, phase I/II trial of pembrolizumab after CTL019 for CD19+ lymphomas. Patients will have CD19+ diffuse large B-cell, follicular, or mantle cell lymphomas relapsed/refractory after CTL019. 12 total patients will be enrolled. Safety of pembrolizumab (primary endpoint) will be determined using a Bayesian monitoring rule for treatment-related adverse events causing drug discontinuation. Secondary efficacy endpoints include overall response rate and progression-free survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab | Experimental | Single arm, pembrolizumab 200mg IV every 3 weeks until progression/toxicity |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | 200mg intravenously (IV) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting Toxicity | Percentage of subjects who discontinued therapy due to dose-limiting toxicity | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rates | 3 months Overall response rates | 3 months |
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Inclusion Criteria:
Histologically confirmed follicular lymphoma grade 1-3A, diffuse large B cell lymphoma, and mantle cell lymphoma by World Health Organization 2009 classification
Relapsed/refractory lymphoma after CTL019 - Be willing and able to provide written informed consent/assent for the trial.
Age 18 years or older on day of signing informed consent.
Have baseline imaging within 6 weeks of enrollment (CT, MR or PET/CT imaging) and have measurable disease on physical examination or imaging studies.
-- Not pregnant or breastfeeding
Any lesion 1.5 cm in long axis dimension is considered measurable.
Performance status of 0-2 on the ECOG Performance Scale
Demonstrate adequate organ function.
Absolute neutrophil count (ANC) ≥1,000 /mcL
Platelets≥50,000 / mcL
Hemoglobin ≥8 g/dL without transfusion or EPO dependency (within 7 days of assessment)
Serum creatinine OR Measured or calculated a creatinine clearance (aCreatinine clearance should be estimated per institutional standard) (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN.
AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
Exclusion Criteria:
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. An exception will be made for patients who have received CTL019/CTL119 on experimental protocol; these patients will be eligible to enroll once progression of disease or failure to respond is documented by clinical or radiologic assessment.
Patient has received intervening therapy for lymphoma after CTL019/CTL119 infusion.
Has active cytokine release syndrome from CTL019/CTL119 infusion.
Has a known history of active TB (Bacillus Tuberculosis).
Hypersensitivity to pembrolizumab or any of its excipients.
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Toxicities that are disease related will not exclude patients.
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has known history of, or any evidence of active, non-infectious pneumonitis.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Has a history of (non-infectious pneumonitis that required steroids or has current pneumonitis.
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Schuster, MD | Abramson Cancer Center at Penn Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34496014 | Derived | Chong EA, Alanio C, Svoboda J, Nasta SD, Landsburg DJ, Lacey SF, Ruella M, Bhattacharyya S, Wherry EJ, Schuster SJ. Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy. Blood. 2022 Feb 17;139(7):1026-1038. doi: 10.1182/blood.2021012634. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab | Pembrolizumab: 200mg intravenously (IV) |
| 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 | Oct 21, 2018 |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Single Arm | Pembrolizumab: 200mg intravenously (IV) |
| 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 |
| ||||||||||||||||||||
| Sex: Female, Male | 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 | Dose-limiting Toxicity | Percentage of subjects who discontinued therapy due to dose-limiting toxicity | Posted | Number | 95% Confidence Interval | percentage of subjects | 3 years |
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| Secondary | Overall Response Rates | 3 months Overall response rates | Posted | Number | 95% Confidence Interval | percentage of subjects | 3 months |
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Adverse events were collected over 2.5 years, from the initiation of the first patient on therapy (June 7, 2016) through treatment of the last patient (January 11, 2019). All adverse events on individual patients were recorded from the time of first dose of pembrolizumab through completion of the Safety Follow Up Visit. SAEs that occured within 90 days of the end of treatment or before initiation of a new anti-cancer treatment were also followed and recorded.
Adverse events were collected by trained research nurse, with attributions assigned by Investigating physician. AEs were recorded in cumulative AE tables, with final review by Principal Investigator at the conclusion of each subject's trial participation.
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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 | Single Arm | Pembrolizumab: 200mg intravenously (IV) | 0 | 12 | 8 | 12 | 12 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| acidosis | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Cytokine Release Syndrome | Immune system disorders | CTCAE (5.0) | Systematic Assessment |
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| blood bilirubin increased | Hepatobiliary disorders | CTCAE (5.0) | Systematic Assessment |
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| sepsis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| hypercalcemia | Investigations | CTCAE (5.0) | Systematic Assessment |
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| delirium | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
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| fever | General disorders | CTCAE (5.0) | Systematic Assessment |
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| other: odynophagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment | odynophagia |
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| dysphagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| optic disorder | Eye disorders | CTCAE (5.0) | Systematic Assessment |
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| non-cardiac chest pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| tachycardia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
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| atrial fibrillation/atrial flutter | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
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| nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| dry mouth | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| GI disorders, other: odynophagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Bloating | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
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| fever | General disorders | CTCAE (5.0) | Systematic Assessment |
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| infusion related reaction | General disorders | CTCAE (5.0) | Systematic Assessment |
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| lower extremity edema | General disorders | CTCAE (5.0) | Systematic Assessment |
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| Facial pain | General disorders | CTCAE (5.0) | Systematic Assessment |
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| Facial edema (left side) | General disorders | CTCAE (5.0) | Systematic Assessment |
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| Flank pain | General disorders | CTCAE (5.0) | Systematic Assessment |
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| Flu-like symptoms | General disorders | CTCAE (5.0) | Systematic Assessment |
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| gait disturbance | General disorders | CTCAE (5.0) | Systematic Assessment |
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| Infections, other: Zoster | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| Upper respiratory infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| urinary tract infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| Neutropenia | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Anemia | Investigations | CTCAE (5.0) | Systematic Assessment |
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| INR increased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| AST elevated | Investigations | CTCAE (5.0) | Systematic Assessment |
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| ALT elevated | Investigations | CTCAE (5.0) | Systematic Assessment |
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| thrombocytopenia | Investigations | CTCAE (5.0) | Systematic Assessment |
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| alkaline phosphatase elevated | Investigations | CTCAE (5.0) | Systematic Assessment |
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| PTT prolonged | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Blood bilirubin increased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| WBC decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations - Other, Platelets elevated | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations - Other, WBC increased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations - Other, ANC increased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Weight loss | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations, other: low serum total protein | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations, other: elevated urine pH | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations, other: elevated MHC | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Investigations, other: elevated CO2 | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Blood LDH increased | Investigations | CTCAE (5.0) | Systematic Assessment |
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| hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hypoglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hyponatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| hypocalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| dehydration | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Metabolism and nutrition disorders - other, phosphorus elevated | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Synovitis (MCP, middle finger, left hand) | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| pain (back, buttock, right leg / sciatica distribution) | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Lower back pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Neuralgia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Post-herpetic neuralgia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Nervous system - Other, cauda equina syndrome | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Trigeminal nerve disorder | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Confusion | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| Urinary frequency | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| urinary hesitancy | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| urinary retention | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| rash | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Skin disorders, other: inflammation | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ellen Napier, Nurse Pracitioner | University of Pennsylvania, Clinical Research Unit | 215.279.1972 | ellen.napier@pennmedicine.upenn.edu |
| Apr 27, 2020 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 20, 2018 | Apr 27, 2020 | ICF_001.pdf |
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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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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