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10.2 protection of privacy

Participants will be informed of the extent to which their confidential health information generated from this study may be used for research purposes. Following this discussion, they will be asked to sign the HIPAA form and informed consent documents. The original signed document will become part of the participant's medical records, and each participant will receive a copy of the signed document. The use and disclosure of protected health information will be limited to the individuals described in the informed consent document.  
| ECOG Performance Status Scale                                                                                        | Karnofsky Performance Scale         |                                                             |                                                                                |                               |
|----------------------------------------------------------------------------------------------------------------------|-------------------------------------|-------------------------------------------------------------|--------------------------------------------------------------------------------|-------------------------------|
| Grade                                                                                                                | Descriptions                        | Percent                                                     | Description                                                                    |                               |
| 0                                                                                                                    | Normal activity                     | 100                                                         | Normal, no complaints, no evidence of  disease                                 |                               |
| Fully active, able to carry on all predisease performance without                                                                                                                      | 90                                  | Able to carry on normal activity; minor                     |                                                                                |                               |
| restriction                                                                                                          | signs or symptoms of disease        |                                                             |                                                                                |                               |
| 1                                                                                                                    | Symptoms, but ambulatory            | 80                                                          | Normal activity with effort; some signs                                        |                               |
| Restricted in physically strenuous                                                                                   | or symptoms of disease              |                                                             |                                                                                |                               |
| activity, but ambulatory and able to  carry out work of a light or                                                   | 70                                  | Cares for self, unable to carry on normal                   |                                                                                |                               |
| sedentary                                                                                                            | nature                              | (e.g.,                                                      | light                                                                          | activity or to do active work |
| housework, office work)                                                                                              |                                     |                                                             |                                                                                |                               |
| 2                                                                                                                    | In bed < 50% of the time            | 60                                                          | Requires occasional assistance, but is  able to care for most of his/her needs |                               |
| Ambulatory and capable of all selfcare, but unable to carry out any  work activities Up and about more than 50% of  waking hours                                                                                                                      | 50                                  | Requires considerable assistance and  frequent medical care |                                                                                |                               |
| 40                                                                                                                   | Disabled, requires special care and |                                                             |                                                                                |                               |
| 3                                                                                                                    | assistance                          |                                                             |                                                                                |                               |
| In bed > 50% of the time Capable of only limited self-care,  confined to bed or chair more than  50% of waking hours | 30                                  | Severely                                                    | disabled,                                                                      | hospitalization               |
| indicated Death not imminent                                                                                         |                                     |                                                             |                                                                                |                               |
| 4                                                                                                                    | 100% bedridden                      | 20                                                          | Very sick, hospitalization indicated Death not imminent                        |                               |
| Completely disabled Cannot carry on any self-care                                                                    | 10                                  | Moribund, fatal processes progressing                       |                                                                                |                               |
| Totally confined to bed or chair                                                                                     | rapidly                             |                                                             |                                                                                |                               |
| 5                                                                                                                    | Dead                                | 0                                                           | Dead                                                                           |                               |
nct# 04407442
appendix 1 performance status criteria

The UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC) Data and Safety Monitoring Committee (DSMC) is responsible for auditing data quality and participant safety for all HDFCCC institutional clinical trials. A summary of DSMC activities for this trial includes:
Semiannual auditing (depending on trial accrual) Review of serious adverse events Minimum of biennial regulatory auditing
nct# 04407442
2. monitoring and reporting guidelines

Investigators will conduct a continuous review of data and participant safety at monthly site committee meetings where the results of each participant's treatment are discussed and documented in the site committee minutes. All institutional Phase II and III therapeutic trials are audited on a semiannual basis, with all data from twenty percent of the enrolled participants audited by the DSMC Monitor/Auditor. The assigned DSMC Monitor/Auditor will review no more than a total of 10 participant charts during the course of auditing this trial. DSMC Monitor/Auditors will send a follow-up report to the study team within 20 business days after the auditing visit is complete for the PI and the study team to resolve all action items from this report within 20 business days. An abbreviated regulatory review (i.e., reviewing protocol and consent versions, SAEs, PVs, DOA logs, 1572 forms, etc.) will occur at each participant monitoring review; however, a full regulatory review will occur on a biennially basis by the DSMC for regulatory compliance. Auditing of all enrolled participants in these trials will be complete after 20% of enrolled participants have been audited through five cycles of treatment. However, regulatory reviews of the trial, safety reviews (i.e., Serious Adverse Event (SAE) reviews and Protocol Violation (PV) reviews), and audit/inspection preparation (as applicable) will continue until the trial is closed by the IRB.
nct# 04407442
3. review and oversight requirements

All Grade 3-5 adverse events (AEs), whether or not considered to be expected or unexpected and whether or not considered to be associated with the use of the investigational agent(s) or study procedure, will be entered into OnCore®, UCSF's Clinical Trial Management System. Adverse events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) as developed and revised by the Common Therapy Evaluation Program (CTEP) of the National Cancer Institute. Adverse events are further given an assignment of attribution or relationship to investigational agent or study procedure. Attribution categories are:  
**Definite** - The adverse event is clearly related to the investigational agent(s)
or study procedure.  
**Probable** - The adverse event is likely related to the investigational agent(s)
or study procedure.  
**Possible** - The adverse event may be related to the investigational agent(s)
or study procedure.  
**Unrelated** - the adverse event is clearly not related to the investigational agent(s)
or study procedure.
All Grade 3-5 adverse events entered into OnCore® will be reviewed on a monthly basis at the Site Committee meetings. The Site Committee will review and discuss the selected toxicity, the toxicity grade, and attribution assignment.
nct# 04407442
3.2 serious adverse event reporting

By definition, an adverse event is defined as a serious adverse event (SAE) according to the following criteria:
Death. Life-threatening (i.e., results in an immediate risk of death). Requires inpatient hospitalization or prolongation of existing hospitalization, Permanent or significant disability/incapacity Gives rise to a congenital anomaly/birth defect, or cancer, or any experience that suggests a significant hazard, contraindication, side effect, or precaution that may require medical or surgical intervention to prevent one of the outcomes listed above.  
Event occurring in a gene therapy study. Event that changes the risk/benefit ratio of a study. Any other event the Principal Investigator judges to be serious or which would suggest a significant hazard, contraindication, side effect, or precaution.  
Serious adverse event reporting will be in accordance with all IRB regulations. For trials conducted under an investigational new drug (IND) application, the SAE will be reported in accordance with Code of Federal Regulation Title 21 Part 312.32 and will be reported on a Med Watch form. UCSF IRB website for guidance in reporting serious adverse events: https://irb.ucsf.edu/adverse-event Med Watch forms and information: www.fda.gov/medwatch/getforms.htm All serious adverse events are entered into OnCore®, as well as submitted to the IRB (per IRB guidelines). The SAEs are reviewed and monitored by the Data and Safety Monitoring Committee on an ongoing basis and discussed at DSMC meetings, which take place every six weeks. The date the SAE is sent to all required reporting agencies will be documented in OnCore®. If the SAE involves a subject death, and is determined to be possibly, probably or definitely related to the investigational drug or any research related procedure, the event must be reported to the DSMC Chair (or Vice Chair) and DSMC Director within one business day. 3.3 Review of Adverse Event Rates If an increase in the frequency of Grade 3 or 4 adverse events (above the rate reported in the Investigator Brochure or package insert) is noted in the study, the Principal Investigator will notify the DSMC via report at the time the increased rate is identified. The report will indicate if the incidence of adverse events observed in the study is above the range stated in the Investigator Brochure or package insert. If at any time the Investigator voluntarily holds enrollment or stops the study due to safety issues, the DSMC Chair (or Vice Chair) and the DSMC Director must be notified within one business day and the IRB must be notified as per IRB reporting regulations.
nct# 04407442
data and safety monitoring committee

Katie Kelley, MD (DSMC Chair)  
  San Francisco, CA 94158
John McAdams (DSMC Director)  
 UCSF HDFCCC  
 San Francisco, CA 94143
nct# 04407442
appendix 3 prohibited medications list

| Drug                        | Trade name (if applicable)   |           |
|-----------------------------|------------------------------|-----------|
| adalimumab                  | Humira                       |           |
| baricitinib                 | Olumiant                     |           |
| BCG                         | TheraCys and TICE BCG        |           |
| certolizumab                | Cimzia                       |           |
| clozapine                   | Clozaril                     |           |
| deferiprone                 | Ferriprox                    |           |
| etanercept                  | Enbrel                       |           |
| fingolimod                  | Gilenya                      |           |
| golimumab                   | Simponi                      |           |
| infliximab                  | Remicade                     |           |
| leflunomide                 | Arava                        |           |
| natalizumab                 | Tysabri                      |           |
| Samarium                    | sm                           | Quadramet |
| 153 lexidronam siponimod    | Mayzent                      |           |
| Talimogene                  | Imlygic                      |           |
| laherparepvec teriflunomide | Aubagio                      |           |
| thalidomide                 | Thalomid                     |           |
| tofacitinib                 | Xeljanz                      |           |  
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