JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT02706405
Collaborator
AstraZeneca (Industry), Juno Therapeutics, Inc. (Industry), MedImmune LLC (Industry), National Cancer Institute (NCI) (NIH)
30
1
8
54.4
0.6
Study Details
Study Description
Brief Summary
This phase Ib trial studies whether anti-CD19-chimeric antigen receptor (CAR) lentiviral vector-transduced autologous T cells (JCAR014) and durvalumab are safe in combination and can work together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). JCAR014 is made of each patient's immune cells (T cells) that have a new gene added to them in a laboratory, which programs them to kill lymphoma cells. Durvalumab is a type of drug called a monoclonal antibody, targeted to PD-L1 that may help immune cells attack cancer cells more effectively and thus help JCAR014 work better.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
-
To evaluate the safety of JCAR014 in combination with durvalumab in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).
-
To determine the maximum tolerated dose (MTD) of durvalumab in combination with JCAR014.
-
To characterize the pharmacokinetic (PK) profile of JCAR014.
SECONDARY OBJECTIVES:
-
To assess the antitumor activity of JCAR014 in combination with durvalumab in R/R B-cell NHL.
-
To estimate the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients treated with JCAR014 in combination with durvalumab.
-
To characterize the PK profile of durvalumab. IV. To assess the immunogenicity of JCAR014 and durvalumab.
EXPLORATORY OBJECTIVE:
- To assess the pharmacodynamic effects of JCAR014 and durvalumab in blood and within the tumor.
OUTLINE: This is a dose-escalation study of durvalumab administered with a single fixed dose of JCAR014. Patients are assigned to 1 of 2 treatment arms, listed as Groups 1 and 2 below.
LYMPHODEPLETING CHEMOTHERAPY: All patients receive cyclophosphamide and fludarabine intravenously (IV) for 3 days starting approximately on day -5 or day -4.
GROUP I: Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 30 days for 30 months, every 3 months for 12 months, then periodically for at least 15 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Study of JCAR014, Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor, in Combination With Durvalumab (MEDI4736) for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Actual Study Start Date
:
Nov 15, 2016
Actual Primary Completion Date
:
May 28, 2021
Actual Study Completion Date
:
May 28, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group I (JCAR014, durvalumab) Early - Dose Level 2 Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group I (JCAR014, durvalumab) Late- Dose Level 1 Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group I (JCAR014, durvalumab) Late - Dose Level 2 Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group II (durvalumab, JCAR014) - Dose Level 1 Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group II (durvalumab, JCAR014) - Dose Level 2 Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group II (durvalumab, JCAR014) - Dose Level 3 Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group II (durvalumab, JCAR014) - Dose Level 4 Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
| Experimental: Group II (durvalumab, JCAR014) - Dose Level 5 Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Durvalumab
Given IV
Other Names:
Drug: Fludarabine
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Count of Participants Who Experienced Adverse Events [28 days post last infusion of Durvalumab, up to 1 year]
Toxicity graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
- Dose Limiting Toxicity (DLT) Rates [28 days post first infusion of Durvalumab (for participants in Group 1) or 28 days post infusion of JCAR (for participants in Group 2)]
Will be summarized based on the dose limiting toxicity evaluable analysis set. The target toxicity rate for the maximum tolerated dose is 30%. Outcome will be reported as a count of patients in each arm that experienced a DLT.
- Highest Treatment Dose Administered on Study [28 days]
Reporting outcome as the maximum durvalumab dose that we reached on the study. Patients were monitored for 28 days post infusion for dose limiting toxicities. The DLT rate was used to determine dose escalation. The study was terminated prior to reaching the maximum tolerated dose.
- Maximum JCAR014 Cmax by Flow Cytometry [Up to 12 months]
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
- Area Under the Curve (AUC) of JCAR014 by Flow Cytometry [Up to 28 days]
Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28. The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
- Maximum JCAR014 Cmax in Blood by Quantitative Polymerase Chain Reaction (qPCR) Analysis [Up to 12 months]
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
- AUC of JCAR014 Cells by qPCR Analysis [Up to 28 days]
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28.The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
- Time to Loss of JCAR014 Detection in Blood by qPCR Analysis [Up to 12 months, +/- 30 days]
The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product.
Secondary Outcome Measures
- Rate of Complete Response (CR) by Investigator Assessment Using Lugano Criteria [Up to 1 year]
This outcome is a count of participants who experienced a best response of complete response (CR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
- Rate of Partial Response (PR) by Investigator Assessment Using Lugano Criteria [Up to 1 year]
This outcome is a count of participants who experienced a best response of partial response (PR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
- Objective Response Rate by Investigator Assessment Using Lugano Criteria [Up to 1 year]
ORR, defined as a count of participant with a best response of either complete response or partial response. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
- Duration of Response [From first response to progressive disease or death, assessed up to 1 year]
Duration of response will be an average amount of days from first response assessment until progression or death for treated patients. Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment.
- Progression Free Survival [From date of first study treatment to progressive disease or death, assessed up to 1 year]
Outcome will be reported as a count of those who did not progress and did not die while on study.
- Overall Survival [From date of first study treatment to death, assessed up to 1 year]
Outcome will be reported as a count of participants who survived while on study. Survival was assessed up to 1 year.
Other Outcome Measures
- B-cell Depletion in Circulation, Profile of Soluble Circulating Proteins Such as Cytokines and Chemokines, and Changes in the Level of Detectable Soluble PD-L1 [Up to 12 months]
- Change in the Phenotype of Tumor Cells (e.g., Expression of PD-L1) and of the Tumor Microenvironment (e.g., Infiltration by Chimeric Antigen Receptor [CAR] T Cells) [Baseline up to 12 months]
Flow cytometry may be used in the blood, bone marrow, and cerebrospinal fluid (CSF) (if applicable).
- Phenotype and/or Genetic Profile of Endogenous Immune Cells and CAR T Cells [Up to 12 months]
Flow cytometry may be used in the blood, bone marrow, and CSF (if applicable).
- Cmax of Durvalumab in Serum [Up to 12 months]
- AUC of Durvalumab in Serum [Up to 12 months]
- Clearance of Durvalumab in Serum [Up to 12 months]
- Terminal Half-life of Durvalumab in Serum [Up to 12 months]
- Antibodies and Cellular Immune Responses to JCAR014 [Up to 12 months]
Cellular immune responses to JCAR014 will be considered in patients who have two consecutive negative assays for JCAR014 or who have recovered endogenous B cells. Cellular responses to JCAR014 will be evaluated by assessing reactivity of patient peripheral T cells to JCAR014. Peripheral blood will be collected for these studies.
- Anti-drug Antibodies Directed Against Durvalumab [Up to 12 months]
Will be assessed using a validated immunoassay in serum samples.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
INCLUSION CRITERIA FOR SCREENING:
-
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; primary mediastinal B-cell lymphoma (PMBCL); or DLBCL transformed from indolent histology with one of the following:
-
Persistent disease after first-line chemo-immunotherapy
-
Relapse after first-line chemo-immunotherapy and not eligible for autologous hematopoietic stem cell transplant (HCT)
-
Relapse or persistent disease after at least two lines of therapy or after autologous HCT
-
Ability to understand and provide informed consent
INCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:
-
Screening evaluation appropriate for leukapheresis and T-cell collection
-
Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
INCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
-
Successful collection of T cells for JCAR014 manufacturing
-
Documentation of CD19 expression on any prior or current tumor biopsy
-
Internal review of histology
-
Detectable positron emission tomography (PET)-positive disease
-
Karnofsky performance status >= 60%
-
Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
-
Serum creatinine < 1.5 x age-adjusted upper limit of normal (ULN)
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN and total bilirubin =< 2 x ULN
-
Adequate pulmonary function, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air; patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) >= 50% of predicted value or diffusing capacity of the lung for carbon monoxide (DLCO; corrected) >= 40% of predicted value
-
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) >= 35% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA)
-
Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for 90 days after the last dose of study therapy (durvalumab or JCAR014)
-
Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for 90 days after the last dose of study therapy (durvalumab or JCAR014)
Exclusion Criteria:
EXCLUSION CRITERIA FOR SCREENING:
-
Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
-
Planned use of corticosteroids (> 10 mg/day prednisone or equivalent) or other systemic immunosuppression within 4 days prior to leukapheresis; topical and/or inhaled steroids are permitted
-
Prior treatment with any CD19 CAR T-cell therapy
-
Prior allogeneic HCT
-
Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
-
Pregnant or breastfeeding women
-
Known exclusion criteria for leukapheresis, JCAR014, or durvalumab therapy
EXCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:
-
Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
-
Prior treatment with programmed cell death (PD)-1, PD-ligand (L)1, cytotoxic T lymphocyte-associated protein 4 (CTLA 4) targeted therapy, or tumor necrosis factor receptor superfamily (TNFRSF) agonists including CD134 (OX40), CD27, CD137 (4-1BB), and CD357 (glucocorticoid-induced tumor necrosis factor receptor family-related protein [GITR])
-
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., ulcerative colitis, Crohn's disease], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea; autoimmune vasculitis; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within 3 years prior to the planned start of treatment; the following are exceptions to this criterion:
-
Vitiligo
-
Alopecia
-
Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
-
Psoriasis not requiring systemic treatment
-
Other conditions considered to be low risk of serious deterioration by the principal investigator (PI)
-
History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; history of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion, or durvalumab infusion is also excluded
-
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis; history of other organic brain syndrome that in the opinion of the PI or designee is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion or durvalumab infusion
-
History of solid organ transplantation
EXCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:
-
For lymphodepletion chemotherapy, JCAR014 and durvalumab: Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
-
Uncontrolled infection
-
Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvalumab (Note: enrolled patients should not receive live vaccine during the study and for 180 days after the last dose of durvalumab)
-
Planned use of corticosteroids (> 10 mg/day prednisone or equivalent) or other systemic immunosuppression is not permitted within 72 hours prior to JCAR014 infusion; topical and/or inhaled steroids are permitted.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- AstraZeneca
- Juno Therapeutics, Inc.
- MedImmune LLC
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Alexandre Hirayama,
Research Associate,
Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT02706405
Other Study ID Numbers:
- 9457
- NCI-2015-02286
- 9457
- P30CA015704
- R01CA136551
- RG6616001
First Posted:
Mar 11, 2016
Last Update Posted:
Aug 24, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Alexandre Hirayama,
Research Associate,
Fred Hutchinson Cancer Center
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | One patient was enrolled on the trial but did not move on to treatment. They were not assigned to an arm or to a treatment dose level. |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Period Title: Overall Study | ||||||||
| STARTED | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| COMPLETED | 1 | 1 | 3 | 0 | 1 | 2 | 3 | 1 |
| NOT COMPLETED | 4 | 2 | 0 | 1 | 0 | 1 | 3 | 6 |
Baseline Characteristics
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Total of all reporting groups |
| Overall Participants | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 | 29 |
| Age (Count of Participants) | |||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
40%
|
0
0%
|
2
66.7%
|
1
100%
|
0
0%
|
3
100%
|
5
83.3%
|
4
57.1%
|
17
58.6%
|
| >=65 years |
3
60%
|
3
100%
|
1
33.3%
|
0
0%
|
1
100%
|
0
0%
|
1
16.7%
|
3
42.9%
|
12
41.4%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
2
40%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
33.3%
|
3
50%
|
3
42.9%
|
10
34.5%
|
| Male |
3
60%
|
3
100%
|
2
66.7%
|
1
100%
|
1
100%
|
2
66.7%
|
3
50%
|
4
57.1%
|
19
65.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
4
80%
|
3
100%
|
3
100%
|
1
100%
|
1
100%
|
3
100%
|
6
100%
|
7
100%
|
28
96.6%
|
| Unknown or Not Reported |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
3.4%
|
| Asian |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
2
6.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
1
3.4%
|
| White |
5
100%
|
2
66.7%
|
3
100%
|
1
100%
|
1
100%
|
3
100%
|
4
66.7%
|
6
85.7%
|
25
86.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Count of Participants Who Experienced Adverse Events |
|---|---|
| Description | Toxicity graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. |
| Time Frame | 28 days post last infusion of Durvalumab, up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
5
100%
|
3
100%
|
3
100%
|
1
100%
|
1
100%
|
3
100%
|
6
100%
|
7
100%
|
| Title | Dose Limiting Toxicity (DLT) Rates |
|---|---|
| Description | Will be summarized based on the dose limiting toxicity evaluable analysis set. The target toxicity rate for the maximum tolerated dose is 30%. Outcome will be reported as a count of patients in each arm that experienced a DLT. |
| Time Frame | 28 days post first infusion of Durvalumab (for participants in Group 1) or 28 days post infusion of JCAR (for participants in Group 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
14.3%
|
| Title | Highest Treatment Dose Administered on Study |
|---|---|
| Description | Reporting outcome as the maximum durvalumab dose that we reached on the study. Patients were monitored for 28 days post infusion for dose limiting toxicities. The DLT rate was used to determine dose escalation. The study was terminated prior to reaching the maximum tolerated dose. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Treated Patients |
|---|---|
| Arm/Group Description | Arm contains all treated patients on study |
| Measure Participants | 29 |
| Number [mg] |
750
|
| Title | Maximum JCAR014 Cmax by Flow Cytometry |
|---|---|
| Description | Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) - Dose Level 1 | Group I (JCAR014, Durvalumab) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Measure Participants | 3 | 8 | 1 | 1 | 3 | 6 | 6 |
| Mean (Full Range) [CD3+ CAR-T cells/μL] |
201.21
|
13.71
|
8.27
|
3.01
|
13.15
|
18.13
|
7.53
|
| Title | Area Under the Curve (AUC) of JCAR014 by Flow Cytometry |
|---|---|
| Description | Absolute CD4+ and CD8+ CAR-T cell counts were determined by multiplying the percentages of CD3+CD4+CD8-EGFRt+ and CD3+CD4-CD8+EGFRt+ events, respectively, in a viable CD45+ lymphocyte forward/side scatter gate by an absolute lymphocyte count performed on the same day. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28. The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. |
| Time Frame | Up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) - Dose Level 1 | Group I (JCAR014, Durvalumab) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Measure Participants | 3 | 8 | 1 | 1 | 3 | 6 | 6 |
| Mean (Full Range) [Days x CD3+ CAR-T cells/μL] |
844.77
|
104.33
|
47.96
|
32.44
|
90.78
|
160.94
|
71.97
|
| Title | Maximum JCAR014 Cmax in Blood by Quantitative Polymerase Chain Reaction (qPCR) Analysis |
|---|---|
| Description | The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) - Dose Level 1 | Group I (JCAR014, Durvalumab) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Measure Participants | 3 | 8 | 1 | 1 | 3 | 6 | 6 |
| Mean (Full Range) [CAR transgene copies/μg DNA] |
37647.95
|
10043.68
|
3690.24
|
1949.22
|
8295.36
|
27841.31
|
26297.43
|
| Title | AUC of JCAR014 Cells by qPCR Analysis |
|---|---|
| Description | The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Subjects had samples analyzed at approximately days 0, 3, 7, 10, 14, 21, and 28 after CAR-T cell infusion to generate the AUC from day 0 to 28.The areas under the curve of CAR T-cell counts by flow cytometry and qPCR between time points were calculated by using a trapezoidal rule computational algorithm. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. |
| Time Frame | Up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) - Dose Level 1 | Group I (JCAR014, Durvalumab) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Measure Participants | 3 | 8 | 1 | 1 | 3 | 6 | 7 |
| Mean (Full Range) [CAR transgene copies/μg DNA x days] |
296188.95
|
104088.38
|
18710.77
|
16721.68
|
63778.63
|
353471.10
|
389065.24
|
| Title | Time to Loss of JCAR014 Detection in Blood by qPCR Analysis |
|---|---|
| Description | The number of copies of the CAR transgene/μg of DNA in the blood was determined by using quantitative polymerase chain reaction (qPCR) to detect the integrated Flap-EF1⍺ sequence, with a lower limit of detection of 10 transgene copies/μg of DNA. Excluding 1 patient in Group 2 Dose Level 5 who received an out-of-specification JCAR014 product. |
| Time Frame | Up to 12 months, +/- 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed are the participants with documented loss of detection of JCAR014 in blood by qPCR during follow-up. |
| Arm/Group Title | Group I (JCAR014, Durvalumab) - Dose Level 1 | Group I (JCAR014, Durvalumab) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells |
| Measure Participants | 2 | 3 | 1 | 0 | 3 | 2 | 2 |
| Mean (Full Range) [days] |
113
|
191
|
28
|
199
|
183
|
64
|
| Title | Rate of Complete Response (CR) by Investigator Assessment Using Lugano Criteria |
|---|---|
| Description | This outcome is a count of participants who experienced a best response of complete response (CR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 4 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
1
20%
|
1
33.3%
|
2
66.7%
|
0
0%
|
1
100%
|
2
66.7%
|
2
33.3%
|
1
14.3%
|
| Title | Rate of Partial Response (PR) by Investigator Assessment Using Lugano Criteria |
|---|---|
| Description | This outcome is a count of participants who experienced a best response of partial response (PR) by investigator assessment using Lugano criteria. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 4 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
1
20%
|
0
0%
|
1
33.3%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
1
14.3%
|
| Title | Objective Response Rate by Investigator Assessment Using Lugano Criteria |
|---|---|
| Description | ORR, defined as a count of participant with a best response of either complete response or partial response. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 4 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
1
20%
|
1
33.3%
|
2
66.7%
|
0
0%
|
1
100%
|
2
66.7%
|
2
33.3%
|
2
28.6%
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response will be an average amount of days from first response assessment until progression or death for treated patients. Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. |
| Time Frame | From first response to progressive disease or death, assessed up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Total number analyzed will be the patients that progressed or died, excluding those that did not progress or die. 1 patient in Group 1 Early Dose Level 2 could not be analyzed for the outcome because they expired before their first response assessment. |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 2 | 2 | 2 | 0 | 1 | 1 | 4 | 7 |
| Mean (Full Range) [days] |
72.5
|
47.5
|
42
|
35
|
31
|
97.75
|
18.14
|
| Title | Progression Free Survival |
|---|---|
| Description | Outcome will be reported as a count of those who did not progress and did not die while on study. |
| Time Frame | From date of first study treatment to progressive disease or death, assessed up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
2
40%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
2
66.7%
|
2
33.3%
|
0
0%
|
| Title | Overall Survival |
|---|---|
| Description | Outcome will be reported as a count of participants who survived while on study. Survival was assessed up to 1 year. |
| Time Frame | From date of first study treatment to death, assessed up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late- Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells . Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ Central Memory T-lymphocytes JCAR014: Given IV Cyclophosphamide: Given IV Durvalumab: Given IV Fludarabine: Given IV |
| Measure Participants | 5 | 3 | 3 | 1 | 1 | 3 | 6 | 7 |
| Count of Participants [Participants] |
2
40%
|
1
33.3%
|
3
100%
|
0
0%
|
1
100%
|
3
100%
|
3
50%
|
3
42.9%
|
| Title | B-cell Depletion in Circulation, Profile of Soluble Circulating Proteins Such as Cytokines and Chemokines, and Changes in the Level of Detectable Soluble PD-L1 |
|---|---|
| Description | |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change in the Phenotype of Tumor Cells (e.g., Expression of PD-L1) and of the Tumor Microenvironment (e.g., Infiltration by Chimeric Antigen Receptor [CAR] T Cells) |
|---|---|
| Description | Flow cytometry may be used in the blood, bone marrow, and cerebrospinal fluid (CSF) (if applicable). |
| Time Frame | Baseline up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phenotype and/or Genetic Profile of Endogenous Immune Cells and CAR T Cells |
|---|---|
| Description | Flow cytometry may be used in the blood, bone marrow, and CSF (if applicable). |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Cmax of Durvalumab in Serum |
|---|---|
| Description | |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | AUC of Durvalumab in Serum |
|---|---|
| Description | |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Clearance of Durvalumab in Serum |
|---|---|
| Description | |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Terminal Half-life of Durvalumab in Serum |
|---|---|
| Description | |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Antibodies and Cellular Immune Responses to JCAR014 |
|---|---|
| Description | Cellular immune responses to JCAR014 will be considered in patients who have two consecutive negative assays for JCAR014 or who have recovered endogenous B cells. Cellular responses to JCAR014 will be evaluated by assessing reactivity of patient peripheral T cells to JCAR014. Peripheral blood will be collected for these studies. |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Anti-drug Antibodies Directed Against Durvalumab |
|---|---|
| Description | Will be assessed using a validated immunoassay in serum samples. |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 28 days post last infusion of Durvalumab, up to 1 year | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An adverse event (AE) is the development of any untoward medical occurrence or the clinical deterioration of a pre-existing medical condition in a patient or clinical study patient administered a medicinal product (e.g., JCAR014 and/or durvalumab). Reporting of AEs will be based on the Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE version 4.03. | |||||||||||||||
| Arm/Group Title | Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late - Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 | ||||||||
| Arm/Group Description | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - early: start durvalumab no earlier than 7 days after JCAR014. Group 1 Dose Level 1 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive JCAR014 IV over 20-30 minutes on day 0 and durvalumab IV over 60 minutes on day 21 (may occur as early as day 7) and then every 4 weeks for up to 10 doses in the absence of disease progression or unacceptable toxicity. Group 1 - late: start durvalumab no earlier than 21 days after JCAR014 Group 1 Dose Level 2 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 1 is 7.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 2 is 22.5 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 3 is 75 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 4 is 225 mg Durvalumab, up to 2 x 106/kg CAR T cells | Patients receive durvalumab IV over 60 minutes on day -1, JCAR014 IV over 20-30 minutes on day 0, then up to 10 additional doses of durvalumab every 4 weeks in the absence of disease progression or unacceptable toxicity. Group 2 Dose Level 5 is 750 mg Durvalumab, up to 2 x 106/kg CAR T cells | ||||||||
All Cause Mortality |
||||||||||||||||
| Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late - Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/5 (60%) | 2/3 (66.7%) | 0/3 (0%) | 1/1 (100%) | 0/1 (0%) | 0/3 (0%) | 3/6 (50%) | 4/7 (57.1%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late - Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/5 (80%) | 3/3 (100%) | 2/3 (66.7%) | 1/1 (100%) | 0/1 (0%) | 2/3 (66.7%) | 4/6 (66.7%) | 4/7 (57.1%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| FEBRILE NEUTROPENIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| Cardiac disorders | ||||||||||||||||
| SINUS TACHYCARDIA | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| ABDOMINAL PAIN | 0/5 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DUODENAL HEMORRHAGE | 0/5 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| General disorders | ||||||||||||||||
| DEATH NOS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| FEVER | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| MULTI-ORGAN FAILURE | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||
| BILE DUCT STENOSIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Immune system disorders | ||||||||||||||||
| CYTOKINE RELEASE SYNDROME | 2/5 (40%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
| Infections and infestations | ||||||||||||||||
| BACTEREMIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: CENTRAL LINE INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: COAG NEGATIVE STAPHYLOCOCCUS BACTEREMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER,SPECIFY: PARAINFLUENZAE VIRUS INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SEPSIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| ANOREXIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| TUMOR PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| ENCEPHALOPATHY | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| SOMNOLENCE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Renal and urinary disorders | ||||||||||||||||
| HEMATURIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| DYSPNEA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| PLEURAL EFFUSION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vascular disorders | ||||||||||||||||
| HYPOTENSION | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Group I (JCAR014, Durvalumab) Early - Dose Level 2 | Group I (JCAR014, Durvalumab) Late - Dose Level 1 | Group I (JCAR014, Durvalumab) Late - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 1 | Group II (Durvalumab, JCAR014) - Dose Level 2 | Group II (Durvalumab, JCAR014) - Dose Level 3 | Group II (Durvalumab, JCAR014) - Dose Level 4 | Group II (Durvalumab, JCAR014) - Dose Level 5 | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 3/3 (100%) | 3/3 (100%) | 1/1 (100%) | 1/1 (100%) | 3/3 (100%) | 6/6 (100%) | 7/7 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| ANEMIA | 2/5 (40%) | 2 | 2/3 (66.7%) | 10 | 3/3 (100%) | 5 | 1/1 (100%) | 1 | 1/1 (100%) | 1 | 1/3 (33.3%) | 1 | 4/6 (66.7%) | 10 | 4/7 (57.1%) | 12 |
| INVESTIGATIONS - OTHER, SPECIFY: INCREASED NUCLEATED RED BLOOD CELLS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| ATRIAL FIBRILLATION | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| PALPITATIONS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| SINUS BRADYCARDIA | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 6 | 3/3 (100%) | 13 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| SINUS TACHYCARDIA | 3/5 (60%) | 4 | 2/3 (66.7%) | 27 | 2/3 (66.7%) | 3 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 1/3 (33.3%) | 1 | 6/6 (100%) | 13 | 4/7 (57.1%) | 8 |
| SINUS TACHYCARDIA (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SINUS TACHYCARDIA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| TACHYCARDIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| VENTRICULAR ARRHYTHMIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||
| EAR AND LABYRINTH DISORDERS - OTHER, SPECIFY: CERUMEN IMPACTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| TINNITUS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| VERTIGO | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||
| ADRENAL INSUFFICIENCY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HYPOTHYROIDISM | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| BLURRED VISION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| CATARACT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DRY EYE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| EYE DISORDERS - OTHER, SPECIFY: PTOSIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| FLOATERS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| ABDOMINAL PAIN | 0/5 (0%) | 0 | 2/3 (66.7%) | 19 | 2/3 (66.7%) | 3 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 2/3 (66.7%) | 4 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
| ABDOMINAL PAIN (AND DISCOMFORT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| ABDOMINAL PAIN, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| ANAL HEMORRHAGE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| BLOATING | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| CONSTIPATION | 2/5 (40%) | 2 | 3/3 (100%) | 9 | 3/3 (100%) | 3 | 1/1 (100%) | 1 | 1/1 (100%) | 3 | 2/3 (66.7%) | 2 | 5/6 (83.3%) | 6 | 4/7 (57.1%) | 9 |
| CONSTIPATION, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DIARRHEA | 1/5 (20%) | 2 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 3 | 4/6 (66.7%) | 5 | 2/7 (28.6%) | 2 |
| DIARRHEA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 1/7 (14.3%) | 1 |
| DRY MOUTH | 2/5 (40%) | 3 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 3/7 (42.9%) | 3 |
| DUODENAL HEMORRHAGE | 0/5 (0%) | 0 | 1/3 (33.3%) | 5 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DYSPEPSIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 3/6 (50%) | 3 | 1/7 (14.3%) | 1 |
| DYSPHAGIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/7 (14.3%) | 1 |
| DYSPHAGIA (INCREASED) | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| FECAL INCONTINENCE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| GASTROESOPHAGEAL REFLUX DISEASE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| GASTROINTESTINAL DISORDERS - OTHER, SPECIFY: GASTROESOPHAGEAL REFLUX DISEASE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GASTROINTESTINAL PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HEMORRHOIDS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: ABDOMINAL TENDERNESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INTERMITTENT ABDOMINAL PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INTERMITTENT DIARRHEA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUCOSITIS ORAL | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| NAUSEA | 2/5 (40%) | 3 | 3/3 (100%) | 13 | 2/3 (66.7%) | 4 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 3/3 (100%) | 12 | 5/6 (83.3%) | 8 | 5/7 (71.4%) | 9 |
| NAUSEA (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| NAUSEA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| STOMACH PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| VOMITING | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 5 | 1/6 (16.7%) | 2 | 4/7 (57.1%) | 7 |
| VOMITTING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| WORSENING OF CONSTIPATION | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| General disorders | ||||||||||||||||
| BRUISING (INJECTION SITE) | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| BRUISING (PICC SITE) | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| CHILLS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 |
| EDEMA | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| EDEMA LIMBS | 0/5 (0%) | 0 | 2/3 (66.7%) | 10 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 3/7 (42.9%) | 6 |
| EDEMA TRUNK | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 2 |
| FATIGUE | 4/5 (80%) | 17 | 3/3 (100%) | 11 | 3/3 (100%) | 9 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 3/3 (100%) | 11 | 6/6 (100%) | 17 | 6/7 (85.7%) | 20 |
| FATIGUE (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| FATIGUE, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| FEVER | 2/5 (40%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 3 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| FLU LIKE SYMPTOMS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| FLU-LIKE SYMPTOMS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: RIGORS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: COLD SENSATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: NODULE ON L SOLE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: TROUBLE GETTING WARM | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| GENERAL DISORDERS AND SITE ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: TIGHTNESS IN CHEST | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GENERALIZED BODY PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HYPOTHERMIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: HICKMAN LINE RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: PORT RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: PORT SITE IRRITATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: REDNESS AT PICC SITE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MILD ERYTHEMA AND PRURITUS UNDER HICKMAN DRESSING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INTERMITTENT FEVERS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MALAISE | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 2 | 1/7 (14.3%) | 1 |
| METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY: EARLY SATIETY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| NON-CARDIAC CHEST PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 |
| PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| PORT SITE IRRITATION | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PORT SITE PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RIGORS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: ERYTHEMA AT HICKMAN SITE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: HICKMAN LINE RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: HICKMAN LINE RASH, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: LINE BANDAGE SITE BLISTER | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: PICC RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: PIV RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||
| HEPATOBILIARY DISORDERS - OTHER, SPECIFY: CHOLELITHIASIS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HEPATOBILIARY DISORDERS - OTHER, SPECIFY: GALLSTONE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Immune system disorders | ||||||||||||||||
| CYTOKINE RELEASE SYNDROME | 2/5 (40%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| IMMUNE SYSTEM DISORDERS - OTHER, SPECIFY: HYPOGAMMAGLOBULINEMIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| IMMUNE SYSTEMS DISORDERS- OTHER, SPECIFY: HYPOGAMMAGLOBULINEMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| CELLULITIS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| ENTEROCOLITIS INFECTIOUS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: BACTEREMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: CENTRAL LINE INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: ORAL THRUSH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: PARAINFLUENZA 2 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: PARAINFLUENZA 4 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: RESPIRATORY SYNCYTIAL VIRUS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER,SPECIFY: BACTEREMIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: HICKMAN SITE INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| LUNG INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| MUCOSAL INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| OROPHARANGEAL CANDIDIASIS | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PAPULOPUSTULAR RASH | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PHARYNGITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| RHINOVIRUS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SEPSIS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SINUSITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| UPPER RESPIRATORY INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| URINARY TRACT INFECTION | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| VASCULAR DISORDERS - OTHER, SPECIFY: SEPTIC PULMONARY EMBOLI | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| WOUND INFECTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| BRUISING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 3 | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 3 |
| BRUISING, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| DERMATITIS RADIATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| FALL | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: FLEA BITES | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFUSION RELATED REACTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: BIOPSY SITE PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: PAIN AT BIOPSY SITE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: PAIN FROM BONE MARROW ASPIRATE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: TORN MENISCUS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INJURY, POISONING, AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY: CUT ON LEFT FINGER | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY: FINGER INJURY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: ABRASION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Investigations | ||||||||||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 2 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| BLOOD BILIRUBIN INCREASED | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 1/7 (14.3%) | 1 |
| CARDIAC DISORDERS - OTHER, SPECIFY: SYSTOLIC MURMUR | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| CARDIAC TROPONIN I INCREASED | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DECREASED NEUTROPHIL COUNT | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| FIBRINOGEN DECREASED | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| FIBROGEN COUNT DECREASED | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY: ASTROVIRUS TEST POSITIVE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| LYMPHOCYTE COUNT DECREASED | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| NEUTROPHIL COUNT DECREASED | 2/5 (40%) | 3 | 3/3 (100%) | 8 | 3/3 (100%) | 12 | 1/1 (100%) | 1 | 1/1 (100%) | 5 | 3/3 (100%) | 12 | 6/6 (100%) | 14 | 5/7 (71.4%) | 21 |
| PLATELET COUNT DECREASED | 1/5 (20%) | 1 | 1/3 (33.3%) | 8 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/1 (100%) | 6 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 4/7 (57.1%) | 17 |
| WEIGHT GAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| WEIGHT LOSS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| WHITE BLOOD CELL DECREASED | 0/5 (0%) | 0 | 1/3 (33.3%) | 5 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| ANOREXIA | 3/5 (60%) | 5 | 3/3 (100%) | 10 | 1/3 (33.3%) | 2 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 1/3 (33.3%) | 4 | 5/6 (83.3%) | 12 | 4/7 (57.1%) | 7 |
| ANOREXIA (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| ANOREXIA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DEHYDRATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| HYPERGLYCEMIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 2/7 (28.6%) | 7 |
| HYPERNATREMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| HYPOALBUMINEMIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HYPOCALCEMIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| HYPOKALEMIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 1/1 (100%) | 3 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 3/6 (50%) | 10 | 3/7 (42.9%) | 4 |
| HYPOMAGNESAEMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HYPOMAGNESEMIA | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 6 | 2/7 (28.6%) | 3 |
| HYPONATREMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 4 | 1/7 (14.3%) | 1 |
| HYPOPHOSPHATEMIA | 1/5 (20%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/7 (14.3%) | 1 |
| INVESTIGATIONS - OTHER, SPECIFY: HYPERLIPIDEMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INVESTIGATIONS - OTHER, SPECIFY: IRON DEFICIENCY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| INVESTIGATIONS -OTHER, SPECIFY: IRON DEFICIENCY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY: HYPERPHOSPHATEMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY: TYPE 2 DIABETES MELLITUS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY: GOUT PAIN | 0/5 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RENAL AND URINARY DISORDERS - OTHER, SPECIFY: GOUT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| ARTHRALGIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 2/3 (66.7%) | 2 | 3/6 (50%) | 3 | 0/7 (0%) | 0 |
| ARTHRALGIA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| BACK PAIN | 3/5 (60%) | 6 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 1/1 (100%) | 2 | 2/3 (66.7%) | 3 | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 7 |
| BILATERAL KNEE JOINT PAIN | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| BONE PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| FLANK PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY: HIP BURSITIS | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| GENERALIZED MUSCLE WEAKNESS | 0/5 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 6 | 2/7 (28.6%) | 2 |
| GENERALIZED MUSCLED WEAKNESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| LEFT LEG BONE PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| LEFT SHOULDER PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE - OTHER, SPECIFY: LEFT WRIST TENDONITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY: RIGHT HIP PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: BACK STIFFNESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: EXERCISE INDUCED MUSCLE PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: HIP PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 3 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: JAW PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: JOINT PAIN DUE TO GARDENING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: MUSCLE SORENESS AFTER ACTIVITY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: MYALGIA AFTER EXERCISE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: RIGHT FOOT PAIN | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - OTHER, SPECIFY: SHOULDER PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| MYALGIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 |
| NECK PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| NECK PAIN, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| RIB PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| WORSENING OF LLQ BACK PAIN | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| SKIN AND SUBCUTANEOUS SKIN DISORDERS - OTHER, SPECIFY: BASAL CELL LESION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| TUMOR PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 2 | 0/3 (0%) | 0 | 2/6 (33.3%) | 4 | 3/7 (42.9%) | 8 |
| Nervous system disorders | ||||||||||||||||
| COGNITIVE DISTURBANCE | 0/5 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 2 |
| DEPRESSED LEVEL OF CONSCIOUSNESS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DIZZINESS | 2/5 (40%) | 3 | 2/3 (66.7%) | 9 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 3/3 (100%) | 6 | 2/6 (33.3%) | 3 | 3/7 (42.9%) | 6 |
| DIZZINESS (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DIZZINESS, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| DYSARTHRIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| DYSGEUSIA | 1/5 (20%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| ENCEPHALOPATHY | 1/5 (20%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| EYE DISORDERS - OTHER, SPECIFY: HORNER'S SYNDROME | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| GASTROINTESTINAL DISORDERS - OTHER, SPECIFY: HYPEROSMIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| HEADACHE | 2/5 (40%) | 3 | 0/3 (0%) | 0 | 3/3 (100%) | 4 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 4/6 (66.7%) | 6 | 4/7 (57.1%) | 9 |
| HEADACHE, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| HYPERSOMNIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| INTERMITTENT DIZZINESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INTERMITTENT PARESTHESIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| LETHARGY | 0/5 (0%) | 0 | 1/3 (33.3%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| LETHARGY, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| MEMORY IMPAIRMENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY: MIGRAINE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 10 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY: ULNAR NERVE FINGER NUMBESS WITH SHOULDER ABDUCTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| PARATHESIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PARESTHESIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PERIPHERAL NEUROPATHY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| PERIPHERAL NEUROPATHY (HANDS) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| PERIPHERAL NEUROPATHY, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| PERIPHERAL SENSORY NEUROPATHY | 1/5 (20%) | 3 | 2/3 (66.7%) | 8 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 2 |
| PERIPHERAL SENSORY NEUROPATHY, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| PRESYNCOPE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| SOMNOLENCE | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| TREMOR | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| TREMORS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| AGITATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| ANXIETY | 1/5 (20%) | 1 | 2/3 (66.7%) | 3 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 3 | 3/7 (42.9%) | 4 |
| ANXIETY, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
| CONFUSION | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 3 |
| DELIRIUM | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DEPRESSION | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 3/7 (42.9%) | 3 |
| INSOMNIA | 2/5 (40%) | 3 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 3/6 (50%) | 3 | 4/7 (57.1%) | 7 |
| INSOMNIA (INTERMITTENT) | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INSOMNIA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| INTERMITTENT ANXIETY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| INTERMITTENT INSOMNIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PSYCHIATRIC DISORDERS - OTHER, SPECIFY: FLAT AFFECT | 0/5 (0%) | 0 | 1/3 (33.3%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RESTLESSNESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| ACUTE KIDNEY INJURY | 1/5 (20%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| DYSURIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HEMATURIA, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RENAL AND URINARY DISORDERS - OTHER, SPECIFY: DYSURIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RENAL AND URINARY DISORDERS - OTHER, SPECIFY: HYDRONEPHROSIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RENAL AND URINARY DISORDERS - OTHER, SPECIFY: NOCTURIA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RENAL AND URINARY DISORDERS - OTHER,SPECIFY: NOCTURIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RENAL CALCULI | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| URINARY FREQUENCY | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 1/3 (33.3%) | 3 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| URINARY HESITANCY | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| URINARY INCONTINENCE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| URINARY RETENTION | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| URINARY TRACT OBSTRUCTION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Reproductive system and breast disorders | ||||||||||||||||
| GENITAL EDEMA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| RENAL AND URINARY DISORDERS - OTHER, SPECIFY: BENIGN PROSTATIC HYPERPLASIA | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS - OTHER, SPECIFY: NIPPLE PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS - OTHER,SPECIFY: VAGINAL BLEEDING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| VAGINAL DISCHARGE | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| VAGINAL PAIN | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| ALLERGIC RHINITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| ALLERGIC RHINITIS, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| ALLERGIC RHITINITIS, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| ASPIRATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| ATELECTASIS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| COUGH | 3/5 (60%) | 4 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 1/1 (100%) | 3 | 3/3 (100%) | 3 | 3/6 (50%) | 4 | 2/7 (28.6%) | 4 |
| DSYPNEA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DYSPNEA | 2/5 (40%) | 3 | 2/3 (66.7%) | 6 | 3/3 (100%) | 4 | 0/1 (0%) | 0 | 1/1 (100%) | 4 | 1/3 (33.3%) | 1 | 4/6 (66.7%) | 7 | 3/7 (42.9%) | 7 |
| EPISTAXIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 3/6 (50%) | 4 | 1/7 (14.3%) | 1 |
| HOARSENESS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| HYPOXIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 |
| INTERMITTENT COUGH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| NASAL CONGESTION | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| NASAL CONGESTION, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| PLEURAL EFFUSION | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 4 | 2/7 (28.6%) | 3 |
| PNEUMOTHORAX | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| POST NASAL DRIP | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| POSTNASAL DRIP | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| PRODUCTIVE COUGH | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RESPIRATORY FAILURE | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY: TACHYPNEA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY: BRADYPNEA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY: HEMOPTYSIS | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RHINORRHEA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SORE THROAT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 3/6 (50%) | 5 | 1/7 (14.3%) | 1 |
| WHEEZING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| ALOPECIA | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 2 |
| BULLOUS DERMITITIS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DIAPHORESIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DRY SKIN | 0/5 (0%) | 0 | 3/3 (100%) | 4 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| DRY SKIN INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| DRY SKIN, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| FOREHEAD PRURITIS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| PRURITUS | 1/5 (20%) | 1 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| RASH (BILATERAL FLANKS AND BACK) | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| RASH ACNEIFORM | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| RASH MACULOPAPULAR | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| RASH MACULO-PAPULAR | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 3 | 2/7 (28.6%) | 4 |
| SKIN AND SUBCUTANEOUS CONDITIONS - OTHER, SPECIFY: LOCALIZED ERYTHEMA OF THE NECK | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: RASH | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - LIVEDO RETICULARIS | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: DIAPHORESIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: HEAT RASH | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: INGROWN TOENAIL | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: NIGHT SWEATS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: NIGHT SWEATS, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY: VENOUS STASIS DERMATITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| SKIN NODULE | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SKIN ULCERATION | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| VASCULAR DISORDERS - OTHER, SPECIFY: NIGHT SWEATS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||||||||
| FLUSHING | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| HOT FLASHES | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| HYPERTENSION | 3/5 (60%) | 6 | 0/3 (0%) | 0 | 2/3 (66.7%) | 4 | 1/1 (100%) | 1 | 1/1 (100%) | 5 | 2/3 (66.7%) | 11 | 4/6 (66.7%) | 13 | 5/7 (71.4%) | 16 |
| HYPERTENSION, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| HYPOTENSION | 3/5 (60%) | 5 | 3/3 (100%) | 27 | 2/3 (66.7%) | 2 | 0/1 (0%) | 0 | 1/1 (100%) | 7 | 3/3 (100%) | 8 | 5/6 (83.3%) | 12 | 4/7 (57.1%) | 6 |
| HYPOTENSION, INTERMITTENT | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| RIGHT LEG LYMPHEDEMA | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| SUPERFICIAL THROMBOPHLEBITIS | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| SUPERIOR VENA CAVA SYNDROME | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| THROMBOEMBOLIC EVENT | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Jordan Gauthier |
|---|---|
| Organization | Fred Hutchinson Cancer Center |
| Phone | 2066672713 |
| jgauthier@fredhutch.org |
Responsible Party:
Alexandre Hirayama,
Research Associate,
Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT02706405
Other Study ID Numbers:
- 9457
- NCI-2015-02286
- 9457
- P30CA015704
- R01CA136551
- RG6616001
First Posted:
Mar 11, 2016
Last Update Posted:
Aug 24, 2022
Last Verified:
Aug 1, 2022