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appendix e eligibility checklist

| Eligibility Checklist Date Completed:                                                                                                                                                              | Institution:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Patient ID#:       | Checklist Version #3.0 Dated: 14Jul2017   |           |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|-------------------------------------------|-----------|
| IRB# 345-15                                                                                                                                                                                        | Title: : A Single-center Phase IIa Study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |                    |                                           |           |
| Evaluating the Safety and Tolerability of umbralisib and  Ibrutinib in Patients with Relapsed or Refractory Diffuse  Large B-cell Lymphoma: A Trial of the Lymphoma  Precision Medicine Laboratory | Waiver #:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                    |                                           |           |
| Reference #:  PI: Mathew Lunning, MD Gender: [ ] M [ ] F                                                                                                                                           | Race:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | [ ] White[ ] Black | [ ] Hispanic                              | [ ] Asian |
| [ ] Native American                                                                                                                                                                                | [ ] Other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | [ ] Unknown        |                                           |           |
| Zip Code/country (if not  USA):                                                                                                                                                                    | Primary method of payment information:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      |                    |                                           |           |
| Inclusion Criteria: Response should be YES                                                                                                                                                         | Yes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | No                 | N/A                                       |           |
| 1.                                                                                                                                                                                                 | Histologically confirmed Diffuse Large B-cell Lymphoma (DLBCL) or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | [ ]                | [ ]                                       | 1.        |
| transformed DLBCL                                                                                                                                                                                  |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |                    |                                           |           |
| 2. 2.                                                                                                                                                                                              | Disease status defined as Patients with relapsed or refractory DLBCL that  has relapsed post-transplant or that has been determined to be ineligible or  unsuitable for transplant. Patients must have received at least one prior  systemic therapy.                                                                                                                                                                                                                                                                                                                                                                                                                                                       | [ ]                | [ ]                                       | [ ]       |
| 3.                                                                                                                                                                                                 | Patients must have measurable (> 1.5 cm) or evaluable disease. Baseline  measurements and evaluations must be obtained within 21 days of  registration to the study. Abnormal PET scans will not constitute evaluable  disease, unless verified by CT scan or other appropriate imaging.  Measurable disease must have at least one objective measurable disease  parameter. A clearly defined, bi-dimensionally measurable defect or mass  measuring at least 1.5 cm in diameter on a CT scan will constitute  measurable disease. Proof of lymphoma in the liver is required by a  confirmation biopsy. Skin lesions can be used as measurable disease  provided bi-dimensional measurements are possible | [ ]                |                                           | [ ]       |  
| 4.                                                                                    | Adequate organ system function, defined as follows:                                                                                                                                                                                                                  | [ ]   |     | [ ]   |     |
|---------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------|-----|-------|-----|
| a.                                                                                    | Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L i. By automated or manual review, whichever is greatest                                                                                                                                                               |       |     |       |     |
| b.                                                                                    | Platelets ≥100 x 109 /L: i. Unless due to bone marrow infiltration then eligible if  platelets > 50 x 109 /L)                                                                                                                                                        |       |     |       |     |
| c.                                                                                    | Total bilirubin ≤ 1.5 x upper normal limit if documented hepatic  involvement with lymphoma, or ≤ 5 x upper normal limit if history of  Gilbert's Disease.                                                                                                           |       |     |       |     |
| d.                                                                                    | Alanine aminotransferase (ALT) and aspartate aminotransferase  (AST) ≤2.5 x ULN if no liver involvement or ≤5 x the ULN if  documented liver involvement                                                                                                             |       |     |       |     |
| e.                                                                                    | Creatinine ≤2.0 mg/dL OR calculated creatinine clearance ≥50  mL/min (as calculated by the Cockcroft-Gault method, Appendix B)                                                                                                                                       |       |     |       |     |
| 5.                                                                                    | ECOG performance status ≤2 or expected survival duration of > 2 months                                                                                                                                                                                               | [ ]   |     | [ ]   |     |
| (Appendix C)                                                                          |                                                                                                                                                                                                                                                                      |       |     |       |     |
| 6.                                                                                    | Patients must be ≥19 years of age (the age of consent in Nebraska)                                                                                                                                                                                                   | [ ]   |     | [ ]   |     |
| 7.                                                                                    | Ability to swallow and retain oral medication                                                                                                                                                                                                                        | [ ]   |     | [ ]   |     |
| 8.                                                                                    | Women must not be pregnant or breast-feeding due to teratogenic  effects of therapy All female patients of child-bearing potential must have a negative  serum pregnancy test within 2 weeks prior to treatment to rule out  pregnancy                               | [ ]   |     | [ ]   | [ ] |
| Pregnancy testing is not required for post-menopausal or surgically sterilized  women |                                                                                                                                                                                                                                                                      |       |     |       |     |
| 9.                                                                                    | Male and female patients of reproductive potential must agree to follow  accepted birth control measures throughout the study period and for 30 days  after the last dose of either study drug for females and 3 months after the  last dose of study drug for males | [ ]   |     | [ ]   |     |
| 10. Patient must be able to adhere to the study visit schedule and other protocol     | [ ]                                                                                                                                                                                                                                                                  |       | [ ] | [ ]   |     |
| requirements                                                                          |                                                                                                                                                                                                                                                                      |       |     |       |     |
| 11. Patient must be aware of the neoplastic nature of his/her disease and             | [ ]                                                                                                                                                                                                                                                                  |       | [ ] |       |     |  
11. Patient must be aware of the neoplastic nature of his/her disease and willingly sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study  
| 12. No serious disease or condition that, in the opinion of the investigator, would   | [ ]                                                                            |     | [ ]   |     |
|---------------------------------------------------------------------------------------|--------------------------------------------------------------------------------|-----|-------|-----|
| compromise the patient's ability to participate in the study                          |                                                                                |     |       |     |
| Exclusion Criteria: Response should be NO                                             | Yes                                                                            | No  | N/A   |     |
| 1. Currently receiving cancer therapy (i.e., chemotherapy, radiation therapy,  immunotherapy, biologic therapy, hormonal therapy, and surgery and/or  tumor embolization) or any investigational drug within 7 days of Cycle 1/Day  1, 14 days of Cycle 1/Day 1 for limited palliative radiation, and/or five halflive of an oral therapy Corticosteroid therapy started at least 7 days prior to initiation of treatment  (prednisone ≤10 mg daily or equivalent) is allowed as clinically warranted).  Topical or inhaled corticosteroids are permitted                                                                                       | [ ]                                                                            |     | [ ]   |     |
| 2.                                                                                    | Major surgery or a wound that has not fully healed within 4 weeks of           |     |       |     |
| enrollment                                                                            | [ ]                                                                            |     | [ ]   |     |
| 3.                                                                                    | History of stroke or intracranial hemorrhage within 6 months prior to          | [ ] |       | [ ] |
| enrollment                                                                            |                                                                                |     |       |     |
| 4.                                                                                    | Requires anticoagulation with warfarin or equivalent vitamin K antagonists     | [ ] |       | [ ] |
| (eg, phenprocoumon)                                                                   |                                                                                |     |       |     |
| 5.                                                                                    | Vaccinated with live, attenuated vaccines within 4 weeks of enrollment         | [ ] |       | [ ] |
| 6.                                                                                    | Autologous hematologic stem cell transplant within 3 months of study entry     | [ ] |       | [ ] |
| 7.                                                                                    | Allogeneic hematologic stem cell transplant within 12 months of study entry    | [ ] |       | [ ] |
| 8.                                                                                    | Active graft versus-host disease and must not be on immunosuppression          | [ ] |       | [ ] |
| 9.                                                                                    | Wide field radiotherapy within 28 days of Cycle 1/Day 1 or active side effects | [ ] |       | [ ] |
| of such therapy                                                                       |                                                                                |     |       |     |  
| 10. Active Hepatitis B (HBV) or C (HCV) infection (negative serology required  excluding those with are seropositive due to prior vaccination) and/or known history  of human immunodeficiency virus (HIV)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | [ ]                     |     | [ ]   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|-----|-------|
| 11. Primary central nervous system involvement only                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | [ ]                     |     | [ ]   |
| 12. Require treatment with strong CYP3A inhibitors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | [ ]                     |     | [ ]   |
| [ ]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                         | [ ] |       |
| 13.Known history of drug-induced liver injury, alcoholic liver disease, primary biliary  cirrhosis, ongoing extra-hepatic obstruction caused by stones, cirrhosis of the liver or  portal hypertension 14. Any life-threatening illness, severe and/or uncontrolled medical condition, or  organ system dysfunction, laboratory abnormality, psychiatric illness or other  condition which, in the Investigator's opinion, could compromise the  subject's safety, interfere with the absorption or metabolism of ibrutinib  capsules, put the study outcomes at undue risk or affect their participation  in the study such as: a. Symptomatic, or history of documented congestive heart failure  New York Heart Association (NYHA) functional classification III-IV  (NYHA, Appendix D)  b. QTc >470 msec (unless related to pacemaker) on EKG within 21 days of initiation of treatment c. Angina not well-controlled by medication d. Poorly controlled or clinically significant atherosclerotic vascular  disease including cerebrovascular accident (CVA), transient  ischemic attack (TIA), angioplasty, cardiac or vascular stenting  within 6 months prior to enrollment | [ ]                     |     | [ ]   |
| 15. Prior malignancies within the past 1 years with exception of adequately treated  basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix  or breast; prostate cancer of Gleason Grade 6 or less with stable PSA levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | [ ]                     |     | [ ]   |
| [ ]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                         | [ ] |       |
| 16. Women who are pregnant or breastfeeding.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Women who agree to stop |     |       |
| breastfeeding would be eligible 17. Known hypersensitivity to either study drug (umbralisib or Ibrutinib)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | [ ]                     |     | [ ]   |  
  
  
NOTE: All questions regarding eligibility for potential subjects should be directed to the PI at 402-559-5166.  
Eligibility: **[ ] Patient satisfies all criteria** [ ] Patient not formally eligible, but admitted to this study because (state reason):  
Patient Initials: __________MR or Study ID#______________DOB ________  
  
ELIGIBILITY reviewed and confirmed. Consenting/Treating Investigator Signature _______________________Date_____________ Printed Name of Consenting/Treating Investigator: __________________________
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appendix f oral sublingual and/or

Medication Adherence Standard Procedure (V 1.0 11-25-2013) PURPOSE To provide a means of ensuring oral, sublingual and/or buccal routes of medication adherence to patients while participating in a clinical trial.  
1. A physician's order will be completed by study patients or representative for oral, sublingual and/or buccal administration per IRB approved protocol.  
2. To ensure the consistent and safe administration of medications not given under the direct supervision of study staff (at home), there will be a "Medication Information Sheet" and a calendar to document times of drug administration.  
3. To record medication adherence Study staff will document results of medication reconciliation and or medication return in the patient's chart.  
4. Maintain documentation of medications returned or sent to investigational pharmacy for destruction (if applicable).  
PROCEDURE
1. Protocol specific information regarding the individual medication(s) should be listed on the form "Medication Information Sheet" and given to the patient at the start of the study and throughout treatment if necessary to help ensure adherence. (See Form A)
2. Name, dose and route of each medication should be listed under 'How to take your Medication' on the
"Medication Information Sheet".  
3. Patients will be given a monthly "Medication Calendar". The calendar will have a place for the patient to record the time that the medication(s) were taken. (See Form B for example)
4. The research nurse will review the patient's "Medication Calendar" for adherence to the study regimen for oral medication administration. Adherence will be noted in the patient's chart. Medication reconciliation will be done and if there is medication to be returned/destroyed it will be sent to the Nebraska Medical Center Investigational Pharmacist for return/destruction in accordance to the Nebraska Medical Center Destruction of Investigational product, Policy \#4.860.
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medication information sheet (form a)

IRB\# 345-16 Title of protocol: A Single-center Phase IIa Study Evaluating the Safety and Tolerability of umbralisib (formerly known as TGR-1202) and Ibrutinib in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma: A Trial of the Lymphoma Precision Medicine Laboratory
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you have been enrolled into

Group A: You will take umbralisib 800mg (4 tablets) Day 1-8 Starting day 9, you will take both umbralisib 800mg (4 tablets) and Ibrutinib 560mg (4 capsules) by mouth once a day with a full 8 ounce glass of water until your treating physician tells you to stop. Follow your Medication Calendar that is provided to record your dosing. Group B: You will take Ibrutinib 560mg (4 capsules) Day 1-8 Starting day 9, you will take both umbralisib 800mg (4 tablets) and Ibrutinib 560 mg (4 capsules) by mouth once a day with a full 8ounce glass of water until your treating physician tells you to stop. Follow your Medication Calendar that is provided to record your dosing. Group C: You will take both umbralisib 800mg (4 tablets) and Ibrutinib 560 mg (4 capsules) by mouth once a day with a full 8ounce glass of water until your treating physician tells you to stop. Follow your Medication Calendar that is provided to record your dosing.  
- Umbralisib **should be taken in the AM. (NOTE**: After cycle 2 if no side effects have been seen you can have the option to take umbralisib and Ibrutinib dosing together at the same time of day.)
- **Ibrutinib should be taken in the evening. (NOTE:** After cycle 2 if no side effects have been seen you can have the option to take umbralisib and Ibrutinib dosing together at the same time of day.)
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things to know about your

1. The dose of the study medications will remain the same during your entire treatment, unless your doctor informs you of a change.  
2. If your doctor modifies the dose of either medication for any reason, please record the change on your Medication Calendar (Form B).  
3. You should take your medications at the same time each day with food. 4. You should avoid grapefruit and Seville oranges (Known as "Chinese Bitter Orange", bitter orange, sour orange, bigarade orange, or marmalade orange. The Seville orange variety is used in the production of marmalade/cooking) during treatment, as these can alter the absorption of the medications.  
5. You should swallow the tablets and capsules as a whole, **do not** chew or crush them. 6. If you miss a dose of your medications, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up. If a dose is missed make sure to mark it on your Medication Calendar (Form B).  
7. If vomiting occurs, no attempt should be made to replace the vomited doses.  
Your Doctor is: ___________________________Contact Phone \# _______________ Your Research Nurse is: ___________________________Contact Phone \# _______________ After hours, nights, weekends and holidays please call 402-559-5600 and ask for the Oncologist on call.  
Medication Diary (Form B) Template
(Form B)
Name:
MR
35-16:  Medication Calendar Study ID:
Group A  
| Your TGR-1202 Dose is__   | _. Take_       | _tablets each day.   |      |    |    |    |    |
|---------------------------|----------------|----------------------|------|----|----|----|----|
| Your Ibrutinib Dose is_   | . Take_        | capsules each day.   |      |    |    |    |    |
| Date                      | Time TGR 1202  | Time Ibrutinib       |      |    |    |    |    |
| Tablets taken             | Capsules taken | Notes                |      |    |    |    |    |
| Day                       | Month          | Day                  | Year | AM | PM | AM | PM |
| 2                         | Do not take
Ibrutinib                |                      |      |    |    |    |    |
| 3                         |                |                      |      |    |    |    |    |
| 4                         | during the
first 8 days.                |                      |      |    |    |    |    |
| s                         |                |                      |      |    |    |    |    |
| 6                         |                |                      |      |    |    |    |    |
| 7                         |                |                      |      |    |    |    |    |
| 8                         |                |                      |      |    |    |    |    |
| 9                         |                |                      |      |    |    |    |    |
| 10                        |                |                      |      |    |    |    |    |
| n                         |                |                      |      |    |    |    |    |
| 12                        |                |                      |      |    |    |    |    |
| 13                        |                |                      |      |    |    |    |    |
| 14                        |                |                      |      |    |    |    |    |
| 15                        |                |                      |      |    |    |    |    |
| 16                        |                |                      |      |    |    |    |    |
| 17                        |                |                      |      |    |    |    |    |
| 18                        |                |                      |      |    |    |    |    |
| 19                        |                |                      |      |    |    |    |    |
| 20                        |                |                      |      |    |    |    |    |
| 21                        |                |                      |      |    |    |    |    |
| 22                        |                |                      |      |    |    |    |    |
| 23                        |                |                      |      |    |    |    |    |
| 24                        |                |                      |      |    |    |    |    |
| 25                        |                |                      |      |    |    |    |    |
| 26                        |                |                      |      |    |    |    |    |
| 27                        |                |                      |      |    |    |    |    |
| 28                        |                |                      |      |    |    |    |    |
| 29                        |                |                      |      |    |    |    |    |
| 30                        |                |                      |      |    |    |    |    |
| 31                        |                |                      |      |    |    |    |    |
| 32                        |                |                      |      |    |    |    |    |
| 3                         |                |                      |      |    |    |    |    |
| 34                        |                |                      |      |    |    |    |    |
| 35                        |                |                      |      |    |    |    |    |  
(Form B)
Name:
MR
Study ID.  
| Group B                  |                |                    |      |    |    |    |    |
|--------------------------|----------------|--------------------|------|----|----|----|----|
| Your TGR-1202 Dose is _  | _. Take_       | tablets each day.  |      |    |    |    |    |
| Your Ibrutinib Dose is _ | . Take _       | capsules each day. |      |    |    |    |    |
| Date                     | Time TGR 1202  | Time Ibration .    |      |    |    |    |    |
| Tablets taken            | Capsules taken | No tes             |      |    |    |    |    |
| Day                      | Month          | Day                | Year | AM | PM | AM | PM |
| l                        |                |                    |      |    |    |    |    |
| 2                        | Do not take    |                    |      |    |    |    |    |
| TGR 1202                 |                |                    |      |    |    |    |    |
| 3                        | during the
first 8 days.                |                    |      |    |    |    |    |
| 4                        |                |                    |      |    |    |    |    |
| 5                        |                |                    |      |    |    |    |    |
| 6                        |                |                    |      |    |    |    |    |
| 7                        |                |                    |      |    |    |    |    |
| 8                        |                |                    |      |    |    |    |    |
| 9                        |                |                    |      |    |    |    |    |
| 10                       |                |                    |      |    |    |    |    |
| 11                       |                |                    |      |    |    |    |    |
| 12                       |                |                    |      |    |    |    |    |
| 13                       |                |                    |      |    |    |    |    |
| 14                       |                |                    |      |    |    |    |    |
| 15                       |                |                    |      |    |    |    |    |
| 16                       |                |                    |      |    |    |    |    |
| 17                       |                |                    |      |    |    |    |    |
| 18                       |                |                    |      |    |    |    |    |
| 19                       |                |                    |      |    |    |    |    |
| 20                       |                |                    |      |    |    |    |    |
| 21                       |                |                    |      |    |    |    |    |
| 2                        |                |                    |      |    |    |    |    |
| 23                       |                |                    |      |    |    |    |    |
| 24                       |                |                    |      |    |    |    |    |
| 25                       |                |                    |      |    |    |    |    |
| 26                       |                |                    |      |    |    |    |    |
| 27                       |                |                    |      |    |    |    |    |
| 28                       |                |                    |      |    |    |    |    |
| 29                       |                |                    |      |    |    |    |    |
| 30                       |                |                    |      |    |    |    |    |
| 31                       |                |                    |      |    |    |    |    |
| 32                       |                |                    |      |    |    |    |    |
| 3                        |                |                    |      |    |    |    |    |
| 34                       |                |                    |      |    |    |    |    |
| 35                       |                |                    |      |    |    |    |    |  
345-16: Medication Calendar
(Form B)
Name:
MR
35-16: Medication Calendar Study ID:
Grow C  
| Your TGR-1202Dose is_        | . Take_        | tab lets each day.   |      |    |    |    |    |
|------------------------------|----------------|----------------------|------|----|----|----|----|
| Your Ibrutinib. Dose is_     | _. Take_       | capsules each day.   |      |    |    |    |    |
| Time TGR 1202 Time Inxutinib |                |                      |      |    |    |    |    |
| Date                         | No tes         |                      |      |    |    |    |    |
| Tablets taken                | Capsules taken |                      |      |    |    |    |    |
| Day                          | Month          | Day                  | Year | AM | PM | AM | PM |
| l                            |                |                      |      |    |    |    |    |
| 2                            |                |                      |      |    |    |    |    |
| 3                            |                |                      |      |    |    |    |    |
| 4                            |                |                      |      |    |    |    |    |
| S                            |                |                      |      |    |    |    |    |
| 6                            |                |                      |      |    |    |    |    |
| 7                            |                |                      |      |    |    |    |    |
| 8                            |                |                      |      |    |    |    |    |
| 9                            |                |                      |      |    |    |    |    |
| 10                           |                |                      |      |    |    |    |    |
| ll                           |                |                      |      |    |    |    |    |
| 12                           |                |                      |      |    |    |    |    |
| 13                           |                |                      |      |    |    |    |    |
| 14                           |                |                      |      |    |    |    |    |
| 15                           |                |                      |      |    |    |    |    |
| 16                           |                |                      |      |    |    |    |    |
| 17                           |                |                      |      |    |    |    |    |
| 18                           |                |                      |      |    |    |    |    |
| 19                           |                |                      |      |    |    |    |    |
| 20                           |                |                      |      |    |    |    |    |
| 21                           |                |                      |      |    |    |    |    |
| 2                            |                |                      |      |    |    |    |    |
| 23                           |                |                      |      |    |    |    |    |
| 24                           |                |                      |      |    |    |    |    |
| 25                           |                |                      |      |    |    |    |    |
| 26                           |                |                      |      |    |    |    |    |
| 27                           |                |                      |      |    |    |    |    |
| 28                           |                |                      |      |    |    |    |    |
| 29                           |                |                      |      |    |    |    |    |
| 30                           |                |                      |      |    |    |    |    |
| 31                           |                |                      |      |    |    |    |    |
| 32                           |                |                      |      |    |    |    |    |
| 33                           |                |                      |      |    |    |    |    |
| 34                           |                |                      |      |    |    |    |    |
| 35                           |                |                      |      |    |    |    |    |  
(Form B)  
| Name:     |
|-----------|
| MR:       |
| Study ID. |  
35-16: Medication Calendar Cycle
(Any Group)  
| Your TGR-1202Dose is_   | . Take_                     | tablets each day.   |      |    |    |    |    |
|-------------------------|-----------------------------|---------------------|------|----|----|----|----|
| Your Ibruting Dose is_  | . Take_                     | cap sules each day. |      |    |    |    |    |
| Date                    | Time TGR 1202 Time Drutinin | No tes              |      |    |    |    |    |
| Tablets taken           | Capsules taken              |                     |      |    |    |    |    |
| Day                     | Month                       | Day                 | Year | AM | PM | AM | PM |
| l                       |                             |                     |      |    |    |    |    |
| 2                       |                             |                     |      |    |    |    |    |
| 3                       |                             |                     |      |    |    |    |    |
| 4                       |                             |                     |      |    |    |    |    |
| 5                       |                             |                     |      |    |    |    |    |
| 6                       |                             |                     |      |    |    |    |    |
| 7                       |                             |                     |      |    |    |    |    |
| 8                       |                             |                     |      |    |    |    |    |
| 9                       |                             |                     |      |    |    |    |    |
| 10                      |                             |                     |      |    |    |    |    |
| ll                      |                             |                     |      |    |    |    |    |
| 12                      |                             |                     |      |    |    |    |    |
| 13                      |                             |                     |      |    |    |    |    |
| 14                      |                             |                     |      |    |    |    |    |
| 15                      |                             |                     |      |    |    |    |    |
| l lo                    |                             |                     |      |    |    |    |    |
| 17                      |                             |                     |      |    |    |    |    |
| 18                      |                             |                     |      |    |    |    |    |
| 19                      |                             |                     |      |    |    |    |    |
| 20                      |                             |                     |      |    |    |    |    |
| 21                      |                             |                     |      |    |    |    |    |
| 22                      |                             |                     |      |    |    |    |    |
| 23                      |                             |                     |      |    |    |    |    |
| 24                      |                             |                     |      |    |    |    |    |
| 25                      |                             |                     |      |    |    |    |    |
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untitled h1
appendix g blood and tissue

Description of Sample Collection: No therapeutic intervention will be undertaken and the results of these studies will not have any influence on the medical management of the subjects.
untitled h1
lymph node biopsy guidelines day

Collect sample per the IR standard. Per Dr. McBride, it is standard to use a 22g or 25g needle. They determine what size is best, based on the patient. They will provide aspirate per their standard process. Typically, four passes for collection of FNA.  
| Facility                                                                                                                                                                                                                                               | Sample                                                                        | Contact Person(s)   | Date and Time Points   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------|---------------------|------------------------|
| UNMC  Designated  Repository  Laboratory                                                                                                                                                                                                               | Optional                                                                      | Lymph               | Node                   |
| Pathology material:  Lymph node biopsies  obtained via US guided  biopsy of accessible lymph  node at day 0 (pretreatment; core biopsy ),  day 8 (fine needle  aspiration) and end of  treatment (progressive  disease or end of study  treatment—1 year; core  biopsy)                                                                                                                                                                                                                                                        | Keenan Hartert Phone: 402- 559 7921Email:  keenan.hartert@unmc.edu            | Baseline day 0 (pre                     |                        |
| treatment; core biopsy )  Date: ___/___/____ Day 8 (fine needle  aspiration)  Date: ___/___/____ End of treatment  (progressive disease or  end of study treatment—1  year; core biopsy)  Date: ___/___/____                                           |                                                                               |                     |                        |
| UNMC  Designated  Repository  Laboratory                                                                                                                                                                                                               | Keenan HartertPhone: 402- 559-7921 Email:  keenan.hartert@unmc.edu            | Baseline Blood      |                        |
|                                                                                                                                                                                                                                                        | Sample                                                                        |                     |                        |
| (pretreatment = day of  biopsy or initiation of  treatment) Date: ___/___/____                                                                                                                                                                         |                                                                               |                     |                        |
| Mandatory Research blood  specimen: 20 ml EDTA tube  pretreatment (day of  biopsy or initiation of  treatment), day 8, 1 month  (+/- 3 days) and 10ml  EDTA at subsequent  radiographic response  assessments, after cycle  2, 4, 6, 9, and 12. (+/- 7 | Location: UNMC Designated Repository  Laboratory  F&PBCC, 4th floor, Room 379 | Day 8 Blood         |                        |
|                                                                                                                                                                                                                                                        | Sample                                                                        |                     |                        |
| Date: ___/___/____                                                                                                                                                                                                                                     |                                                                               |                     |                        |
| UNMC IRB#345-16 Protocol Version 4.2 Dated 07Oct2019                                                                                                                                                                                                   |                                                                               |                     |                        |  
| days).                                                                                                                      | After Month 12,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |      |     |
|-----------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------|-----|
| efficacy                                                                                                                    | assessments                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |      |     |
| should                                                                                                                      | occur                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | at   | the |
| investigators                                                                                                               | discretion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |      |     |
| with                                                                                                                        | 10ml                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | EDTA |     |
| peripheral blood samples  obtained ONLY IF  FEASIBLE.                                                                       | 1 month (+/- 3 days)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |      |     |
| Blood Sample  Date: ___/___/____  Page 1 of 2  Re-staging Blood  Sample after cycle 2  (+/- 7 days).                        |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |      |     |
| Additional  Optional:                                                                                                       | Please                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |      |     |
| Check the box if patient  consented to the storing of  any leftover peripheral  blood for future unspecified  research use) | Date: ___/___/____  Re-staging Blood  Sample after cycle 4 (+/- 7 days).  Date: ___/___/____  Re-staging Blood  Sample after cycle 6 (+/- 7 days).  Date: ___/___/____  Re-staging Blood  Sample after cycle 9 (+/- 7 days).  Date: ___/___/____  Re-staging Blood  Sample after cycle 12 (+/- 7 days)  Date: ___/___/____ After Month 12, efficacy  assessments should  occur at the  investigators discretion  peripheral blood  samples obtained ONLY  IF FEASIBLE.  Re-staging Blood  Sample  Date: ___/___/____  Re-staging Blood  Sample Date: ___/___/____  Re-staging Blood  Sample Date: ___/___/____ |      |     |  
|                    | Re-staging   | Blood   |
|--------------------|--------------|---------|
| Sample             |              |         |
| Date: ___/___/____ |              |         |