Clinical trial: NCT03045328
Section: Alternatives
Subsections: Alternatives

You do not have to be in this study to receive treatment for your CLL or SLL. Possible alternative treatments and side effects of these treatments depend on the characteristics and stage of your cancer. The effectiveness and side effects of other treatments may be different for different people. Instead of taking part in this study, you may choose to:  
Receive treatment with other chemotherapy drugs, including those approved for use in the US, including fludarabine; bendamustine; rituximab; cyclophosphamide; and others, alone or in combination. There are numerous treatments that may or may not be suitable for the specifics of your cancer.  
Participate in another research study with a different study drug or procedure While your type of cancer may be treatable with currently approved and available medications and procedures, another alternative is to receive only comfort care,  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia also called "palliative care," like painkillers. These types of treatments do not treat your cancer (ie, are not curative), and only make you comfortable (symptom relief). If you think you might prefer comfort care, please discuss this with your family, friends, and doctor. NOTE: The Study Doctors do not recommend this decision for you at this time, although it is and will remain your decision.  
The Study Doctors will discuss with you the risks and benefits of these alternatives, including which other treatments might be suitable for you. If you decide that you do not wish to take part in this study and wish to pursue any of these, or other alternatives, this will not change your regular medical care or the other treatment choices in any way.
Clinical trial: NCT03045328
Section: Confidentiality
Subsections: Confidentiality|Authorization To Use Your Health Information For Research Purposes|What Personal Information Will Be Obtained, Used Or Disclosed?|Who May Use Or Disclose The Information?|Who May Receive Or Use The Information?|When Will My Authorization Expire?|Will Access To My Medical Record Be Limited During The Study?

The results of this research study may be presented at scientific or medical meetings or published in scientific journals. Your identity and/or your personal health information will not be disclosed except as authorized by you or as required by law. However, there is always some risk that even de-identified information might be re-identified. Your research records may be disclosed outside of Stanford, but in this case, you will be identified only by a unique code number. Information about the code will be kept in a secure location and access limited to research study personnel.  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Patient information may be provided to Federal and other regulatory agencies as required. The US FDA, for example, may inspect research records and learn your identity if this study falls within its jurisdiction. The purpose of this research study is to obtain data or information on the safety and effectiveness of venetoclax and ibrutinib. The results will be provided to the drug manufacturers AbbVie Inc. and Pharmacyclics, LLC; their affiliates and collaborators (eg, Janssen Biotech, Inc.); the Food and Drug Administration (FDA); and other federal and regulatory agencies as required.  
  
Approval Date: November 14, 2018 Expiration Date: November 14, 2019
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia

Because information about you and your health is personal and private, it generally cannot be used in this research study without your written authorization. If you sign this form, it will provide that authorization. The form is intended to inform you about how your health information will be used or disclosed in the study. Your information will only be used in accordance with this authorization form and the informed consent form and as required or allowed by law. Please read it carefully before signing it.  
What is the purpose of this research study and how will my health information be utilized in the study? This study may help the drug manufacturers and FDA determine if development of venetoclax plus ibrutinib as a combination treatment should continue. Information from this study will be submitted to the companies supporting this study (AbbVie Inc and Pharmacyclics LLC, and their affiliates and collaborators, eg, Janssen Biotech, Inc.) and international regulatory agencies including the FDA. The results from this research study are expected to be presented at scientific or medical meetings or published in scientific journals. You will not be personally identified in the publications, although representatives of the sponsor and FDA and other international regulatory agencies may need to know who you are. Do I have to sign this authorization form?  
You do not have to sign this authorization form. But if you do not, you will not be able to participate in this research study, including receiving any research-related treatment. Signing the form is not a condition for receiving any medical care outside the study.  
If I sign, can **I revoke it or withdraw from the research later?**
If you decide to participate, you are free to withdraw your authorization regarding the use and disclosure of your health information (and to discontinue any other participation in the study) at any time. After any revocation, your health information will no longer be used or disclosed in  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia the study, except to the extent that the law allows us to continue using your information (eg, necessary to maintain integrity of research). If you wish to revoke your authorization for the research use or disclosure of your health information in this study, you must write to:
Steven E. Coutre, MD 875 Blake Wilbur Dr, MC 5821 Stanford, CA 94305

Your health information related to this study, may be used or disclosed in connection with this research study, including, but not limited to identifiers such as your name and initials; address including ZIP code; phone numbers; dates including date of birth; age; sex; race; ethnicity; Medicare ID number; medical record number (MRN); and other numbers or codes such as your study ID number that might identify you. During the study, researchers will also obtain information about your health status, life-style choices, medical history, and medical diagnoses, including family medical history and allergies; your current and past medications or therapies; your physical examination results including height and weight, blood pressure readings, heart rate, breathing rate and temperature; your laboratory test results including blood, urine, and pregnancy tests; results of procedures, such as cancer assessments, medical scans including MRI
and CT scans, bone marrow aspiration/biopsy; results of genetic and biomarker testing; and medical reports, such as the discharge summary and radiology, post-operative, and pathology reports. **The** researchers will also get information from your medical record
(including hospital records from the Stanford **Healthcare and your**
referring physician's records).

The following parties are authorized to use and/or disclose your health information in connection with this research study:
The Protocol Director Steven E. Coutre, MD Research Staff The Stanford University Administrative Panel on Human Subjects in Medical Research; the Stanford Data and Safety Monitoring  
  
  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Committee (DSMC); and/or any other unit of Stanford University as necessary

The parties listed in the preceding paragraph may disclose your health information to the following persons and organizations for their use in connection with this research study:  
Pharmacyclics LLC (and its affiliates, eg, Janssen Biotech Inc.), and AbbVie, Inc., or their representatives The Food and Drug Administration (FDA) and/or other state or international regulatory authorities The Office for Human Research Protections (OHRP) in the US Department of Health and Human Services (DHHS)
The US Centers for Medicare & Medicaid Services (CMS), the agency responsible for administration of the Medicare program Government agencies to whom certain diseases (like HIV, hepatitis, and STDs) must be reported
Your information may be re-disclosed by the recipients described above, if they are not required by law to protect the privacy of the information.

Your authorization for the use and/or disclosure of your health information will end on 31 December 2066 or when the research project ends, whichever is earlier.

To maintain the integrity of this research study, you may not have access to any health information developed as part of this study until it is completed.  
At that point, you would have access to such health information if it was used to make a medical or billing decision about you (eg, if included in your official medical record).  
  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia
___________________________________________ ____________
Signature of Adult Participant Date
___________________________________________ Printed Name of Adult Participant ___________________________________________
If *needed*: Signature of Legally Authorized Representative (LAR)
___________________________________________ ____________ Printed Name of LAR Date
___________________________________________ LAR's Authority to Act for Participant
(e.g., parent, guardian, or conservator)
NOTE: If using the Short Form Consent process for informed consent in another language pursuant to an "Alteration of HIPAA Authorization," neither the participant nor their LAR should sign the HIPAA "Authorization To Use Your Health Information For Research Purposes" above.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia
Clinical trial: NCT03045328
Section: Duration of Study Involvement
Subsections: Duration Of Study Involvement

Your treatment in this research study is initially expected to take up to about 117 weeks, followed by continued treatment with ibrutinib alone if you are benefitting. After 117 weeks, you may be able to continue treatment with ibrutinib only until you withdraw from the study, your cancer gets worse (disease progression), or death. Your treatment in this study can continue until one of the following occurs:
You withdraw your agreement to continue to take part in this research study  
You become "lost-to-follow-up" Your cancer becomes worse (disease or tumor progression)
You need a treatment that is not allowed in this study You have a different illness that prevents further administration of study drugs You or your doctor decide that the side effects are too severe You are a woman and have become pregnant The study is terminated or You are removed from the research study for any of the following reasons:
o You do not follow the study team's instructions for the study. o Your Study Doctor determines it is in your best interest.  
o Other unanticipated; appropriate; and/or administrative reasons as determined by your doctor or the study sponsor.
When your participation in this study ends, you may be asked to return for a final visit to have some end-of-study evaluations or tests, or to allow medical information to be collected about your health after the trial treatment is stopped. After you finish the study, or stop taking the study drug for any other reason, you may continue to be checked regularly (physical exams; blood tests; tumor measurements; X-rays; other scans, etc) if you continue to have significant side effects from the treatment. This is called follow-up. Your Study Doctor will follow your progress, in accordance with good medical care, for as long as it is felt to be necessary by both you and the doctor, unless you ask otherwise. Many, if not all, of these procedures will be part of your regular continued medical care.
Clinical trial: NCT03045328
Section: Participant Responsibilities
Subsections: It Is Very Important That You Immediately Tell The Investigator And The Ct Technician If Any Of The Following Apply To You:|Participant Responsibilities

You are or could be pregnant. You have, or previously had, kidney problems.  
You are taking Glucophage (metformin).  
You have any allergies to medications, contrast agents, iodine, or shellfish, or have a history or severe allergies.  
You have recently taken or received barium ("barium study") or bismuth, or have recently taken Pepto-Bismol; Kaopectate; Maalox; Bismatrol; or other digestive aids.  
You have a cardiac pacemaker or any other biomedical device, such as surgical clips, pins; screws; or metal plates in or on your body.  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia You have any body piercings in or near the area of the scan; In some cases, these could mean you should not have a CT scan performed.  
Magnetic Resonance Imaging (MRI): An MRI, which does not require radiation exposure, may be used in place of a CT "X-ray" scan. The MRI will be performed according to standard practice, and will take about 30 to 60 minutes. MRI machines use a powerful magnet and radiofrequency fields to make images of the body interior, and to evaluate blood flow and the extent of the cancer. An MRI scanner is a large, tunnel-shaped machine, and uses a strong magnet and radiofrequency magnetic fields to make images of the body interior. This magnet is very strong, and will attract or pull on some metals and affect some electronic devices, including magnetic access cards, and the magnetic strip on credit / debit /ID cards. Do not bring any metal objects into the magnet room. Any metal objects that you are carrying or have in your body could be a hazard to you or others. Watches; hearing aids or other removable medical devices; jewelry / rings; credit / debit / ID /access cards should be removed. You will be provided a way to secure these items. Because the magnetic field is so strong, tell the study team now, and also tell the MRI operator before entering the MRI room, if any of the following apply to you.

As a participant, your responsibilities include:
Follow the instructions of the Protocol Director and study staff. Drinks lots of water while receiving treatment, especially when taking venetoclax, to help reduce the chance of a specific type of adverse event (tumor lysis syndrome, TLS, discussed later in this document).  
Be sure to tell the study staff all your present and past diseases, allergies and any drugs or medications you are taking. This is for your safety. Other drugs or medications includes all prescription drugs; over-the-counter (OTC) drugs; herbal preparations; and nutritional supplements. These may interact with the study drugs. If any other medical provider prescribes new medications for you while you are on this study, please contact the study staff before taking the new medicine, or have that medical provider contact the study staff before prescribing it to you. You should not take any new non-prescription medicine while you are on this study unless you first check with the study staff. See the following precautions. The Study Team will give you more information.  
Venetoclax should not be taken with CYP3A inhibitors or potent CYP3A inducers such as warfarin or rifampin.  
Venetoclax should be taken with **caution when** using **weak or moderate CYP3A inducers,** or CYP2C8 and CYP2C9 substrates.  
Also, do not eat grapefruit or grapefruit products; Seville **oranges or** products such as marmalade containing Seville **oranges; or** star fruit from 3 days before your first dose of venetoclax through the last day of venetoclax treatment, completed due to possible metabolic interactions between the fruit and venetoclax .  
Come to the Study Visits as scheduled. Take the Study Drugs as instructed.  
Maintain control of the Study Drugs, and keep them in a safe place where children cannot access them. Follow any additional storage instructions that you are provided with.  
Ask questions as you think of them. Keep your study appointments. If it is necessary to miss an appointment, please contact the Protocol Director or research study staff to reschedule as soon as you know you will miss the appointment.  
Tell the Protocol Director or study team if you change your mind about staying in the study.  
Tell the Protocol Director or study team about any side effects, doctor visits, or hospitalizations that you may have.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia  
Tell the Protocol Director or study team if you believe you might be pregnant or gotten your partner pregnant.  
Do not breast-feed an infant. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ibrutinib, breast-feeding should be discontinued during ibrutinib treatment.  
You must use a medically-approved method of birth control, preferably a barrier method, for the duration of the treatment period and for at least 1 month after the last day you receive the Study Drug.  
Keep, complete, and return your study diaries as instructed.
Clinical trial: NCT03045328
Section: Participant's Rights
Subsections: Participant'S Rights|Experimental Subject'S Bill Of Rights

You should not feel obligated to agree to participate. Your questions should be answered clearly and to your satisfaction. If you decide not to participate, tell the Study Director. You can also tell any other member of the study staff. You will be told of any important new information that is learned during the course of this research study, which might affect your condition or your willingness to continue participation in this study. After you hear about this information, you have the right to withdraw from the program.

As a research participant you have the following rights. These rights include but are not limited to the participant's right to:
Be informed of the nature and purpose of the experiment;  
Be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized; Be given a description of any attendant discomforts and risks reasonably expected; Be given an explanation of any benefits to the subject reasonably to be expected, if applicable; Be given a disclosure of any appropriate alternatives, drugs or devices that might be advantageous to the subject, their relative risks and benefits; Be informed of the avenues of medical treatment, if any available to the subject after the experiment if complications should arise; Be given an opportunity to ask questions concerning the experiment or the procedures involved; Be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation without prejudice; Be given a copy of the signed and dated consent form; and Be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion or undue influence on the subject's decision.  
  
Approval Date: November 14, 2018 Expiration Date: November 14, 2019
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia May we contact you about future studies that may be of interest to you? ___Yes ___No Signing your name means you agree to be in this study and that you will receive a copy of this signed and dated consent form. _______________________________________________ Printed Name of **Adult Participant** _______________________________________________ ____________ Signature of Adult Participant Date _______________________________________________ If needed: Printed Name of **Legally Authorized Representative** (LAR) _______________________________________________ ____________ Signature of LAR Date _______________________________________________ LAR's Authority to Act for Participant (eg, parent, guardian, or conservator)
Clinical trial: NCT03045328
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: It Is Very Important That You Immediately Tell The Investigator And The Mri Operator If You Have A Cardiac Pacemaker Or Any Other Biomedical Device In Or On Your Body.|If You Feel Discomfort At Any Time, Notify The Operator And You Can Discontinue The Exam At Any Time. Women Of Childbearing Potential|Possible Risks, Discomforts, And Inconveniences|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|Reduced Blood Levels Of Infection-Fighting Cells (Neutropenia)|Other Blood Effects|Reproductive Effects|Second Cancer|Use With Other Medications, Including Vaccines|Use With Other Medications, Including Vaccines|Unlikely Side Effects (These Side Effects Occurred In At Least 1 In Every 100 People Taking Ibrutinib; 1% Or More)|Taking Ibrutinib; Less Than 1%)|Serious Side Effects Of Ibrutinib - Contact Your Study Doctor Immediately.|Effects On The Heart|Interstitial Lung Disease (Ild)|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|Non-Melanoma Skin Cancer And Other Cancers|Non-Melanoma Skin Cancer And Other Cancers|Hypertension|Infections|Bleeding Effects|Lymphocytosis And Leukostasis|Decreased Blood Counts|Liver Failure|Allergic Reactions|Rash|Interference With Other Drugs|Other Serious Side Effects Of Ibrutinib Lymphocytosis And Leukostasis (Increases In Wbc)|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|Tumor Lysis Syndrome (Tls)|High Blood Pressure (Hypertension)|Non-Melanoma Skin Cancer And Other Cancers|Non-Melanoma Skin Cancer And Other Cancers|Use With Other Medications, Including Vaccines|Use With Other Medications, Including Vaccines|Risks Of Ibrutinib During The Maintenance Phase

You have any other metal objects in or on your body, such as:  
Metal plates; pins; screws; surgical clips Medical devices, including hearing aids Other implants Metal fragments in your body, such as bullet fragments or shrapnel fragments Piercings You have ever had a head or eye injury involving metal fragments You have ever worked in a metal or fabrication shop
You have a history of severe allergies, or have previously had a reaction to a Gadolinium-based contrast agents You have, or previously had, kidney problems You are or could be pregnant In some cases, these could mean you should not have an MRI scan performed The scanning procedure is very much like an X-ray, but uses a strong magnetic field instead of X-rays. You will not be able to feel the magnetic field. You will be asked to lie on a long narrow bench for up to 45 minutes while the machine performs the scan. You will be asked not to move during the scan and to relax and breathe normally. During this time, you will not be exposed to X-rays, but rather the magnetic field. During the  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia  
  
scan, the bench you are lying on will move into a narrow space in the scanner.  
Many steps have been taken to make the procedure comfortable, but you may still experience some discomfort or anxiety ("claustrophobia") from being in this confined space. If this bothers you too much, the study team may provide you with a medication to help you stay calm. The scanner will make repetitive tapping noises, which can seem very loud inside the scanner. You may be provided with earplugs or headphones to wear.

If you are pregnant or currently breast-feeding, you may not participate in this study. It is not known whether the Study Drug is safe for fetuses or breast-fed babies. A pregnancy test, as described above, will be conducted. Location: The location of the Screening Visit will be in the Stanford Cancer Center Clinics at 875 Blake Wilbur Dr, or as otherwise directed by study staff. Medical imaging may be performed at the following clinic locations. The Study Team will let you know which locations you need to go to:
Stanford Hospital Stanford Cancer Center, MRI department, ground floor Blake Wilbur Building 300 Pasteur Dr Radiology, ground floor Stanford, CA 94305 900 Blake Wilbur Dr Phone (650) 723-6855 Palo Alto, CA 94306 Phone (650) 723-6855 Stanford Medicine Outpatient Center Stanford Medicine Imaging Center Pavilion B 451 Sherman Ave 450 Broadway St Palo Alto, CA 94306 Redwood City, CA 94063 Phone (650) 723-6855 Phone (650) 723-6855

There are risks, discomforts, and inconveniences associated with any research study. This section describes the reasonably foreseeable risks; discomforts; and inconveniences that you may experience. In addition, because this is a research study, there may be risks that are not yet known ("unforeseeable"), including a risk of death due to unknown risks. These deserve careful thought.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia You should talk with the Study Doctor if you have any questions. If you do not understand what any of the words in this section or elsewhere mean, please ask the Study Doctor or study staff to explain these terms to you. You must tell the Study Doctor or Study Team about all side effects that you have. If you experience serious problems, you may be asked to return to the study center for more tests. Furthermore, due to the risk of side effects resulting from different combinations of drugs (called drug-drug interactions), you must inform the Study Team of any medications you are taking, including over-the-counter medicines or herbal remedies, during the course of the study, and you must also notify the Study Doctor of any other medical treatments or procedures that may be necessary for you to undergo. If you are not honest about your side effects and other medications and procedures, it may not be safe for you to stay in the study. All patients in the study will be monitored for side effects. Your Study Doctor may give you medications or stop the study drug(s) for a short time or reduce their dose to try to help lessen some of the side effects. Each person's reaction to the study drug may be different. You may experience a side effect that could not be predicted by the Study Doctor. Please review the side effects known to be related to the study drug being evaluated in this study. You may experience many, some, or none of the side effects described below. Side effects may be mild, moderate, or severe, and although they usually subside, they could also be permanent. It is possible that a side effect could be fatal. If you experience serious problems, you may be asked to return to the study center for more tests. If you experience the following symptoms of an allergic reaction, contact the Study Doctor or the Study Team **immediately**. If you are in distress, CALL 911 immediately.  
Allergic reaction, including rash, hives and/or itching of the skin, or blisters; increased heart rate (a fast pulse or tachycardia); and/or abnormal or increased sweating Swelling of the face, mouth, lips, gums, tongue and/or neck Wheezing; shortness of breath; or difficulty breathing Dizziness; confusion; feeling light-headed; pounding or racing heart; and/or fainting Fever; chills; weakness; confusion; body aches; cold or flu symptoms; and/or feeling tired Easy bruising and/or bleeding Sudden severe headaches; weakness in the arms or legs; difficulty speaking or understanding speech; and/or loss of balance Yellowing of the eyes and skin (jaundice), dark-colored urine; and/or gray- or clay-colored bowel movement (stools);  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Upset stomach (nausea), loss of appetite; tiredness (fatigue); and/r diarrhea Severe skin reactions and/or rash with blisters and peeling skin or spreads quickly, which may include open ulcers or sores in the mouth and other areas of the body Venetoclax has been administered to at least 567 people with cancer. The following side effects (adverse events) were reported to be related to treatment with venetoclax. Most Common Side Effects of the Study Drug Venetoclax **[these side effects** occurred in more than 1 in 10 **people taking venetoclax (more than 10%)]**
Decreased levels of neutrophils in the blood (cells that help fight infection, neutropenia Decreased levels of red blood cells and/or hemoglobin (anemia)
Decreased levels of platelets in the blood (thrombocytopenia). May cause bruises or even bleeding Upset stomach (nausea)
Diarrhea Upper respiratory tract infection (URI)
Less-likely Side Effects of the Study Drug Venetoclax **[these side effects occurred** in more than 1 in 100 people taking venetoclax **(1% to 10%)]**
Low white blood cell count (WBC, blood cells that help fight infection) with fever
(febrile neutropenia)
Persistent cough with lung inflammation (bronchitis)
Lung infection (pneumonia or similar)
Respiratory tract infection Viral upper respiratory tract infection Lower respiratory tract infection Flu (influenza)
Common cold (nasopharyngitis) Herpes infection (Herpes zoster) Oral herpes Yeast infection of mouth (oral candidiasis)
Other Candida infection (candidiasis)
Urinary tract infection (UTI) Bacterial skin infection, may become serious (cellulitis)
Bacterial infection of the blood (sepsis), a serious condition Reduced levels of calcium in the blood (hypocalcaemia)  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia  
Increased levels of phosphate in the blood (hyperphosphatemia Increased levels of potassium in the blood (hyperkalemia)
Increased levels of uric acid in the blood (hyperuricemia)
Tumor lysis syndrome (additional information below)
Following are specific safety warnings and precautions when taking venetoclax.

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells has occurred with venetoclax treatment, most often right after starting treatment, or if the patient has a large or extensive cancer. The levels of breakdown products in your blood may cause changes in kidney function, abnormal heartbeat, or seizures. This is called tumor lysis syndrome (TLS). Your Study Doctor will give you a medication to reduce the chance of TLS, but may still do blood tests to check for TLS.

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have happened during treatment of cancer and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your study doctor may do blood tests to check for TLS.

Tumor lysis syndrome (TLS), discussed above, may occur with ibrutinib treatment, and may cause changes in kidney function, abnormal heartbeat, or seizures. Your Study Doctor may do blood tests to check for TLS.

Venetoclax treatment may reduce your blood levels of a certain type of white blood cell (WBC), called neutrophils (neutropenia), or in general (leukopenia) in your blood. These types of cells help fight infections, and reduced numbers may mean a greater risk of infection. There may be an increased risk of infection, which can be serious. You may receive an additional medication to help boost the levels of these type of cells.

Venetoclax treatment may reduce your levels of red blood cells (RBC), which is called anemia. This may make you feel weak or tired, or worsen how weak or tired you feel due to other causes. Venetoclax treatment may reduce your blood levels of platelets. This may cause bruises or even bleeding, or worsen how easily you bruise or bleed due to other causes.

Venetoclax treatment may reduce the ability of a man to produce sperm. In dogs, this effect was not reversible after 4 weeks of dosing. If you are a male and may want to have children, you should consider sperm banking before treatment with venetoclax. The study team can provide you with more information.

At least 10 people receiving venetoclax have developed a second, new cancer (a different cancer not the same as the first disease). This number does not include  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia instances of skin cancer that was not melanoma. Most patients had one or more other risk factors, such as being elderly or having received multiple prior therapies. No pattern was apparent, and no instances of 2 nd cancer were considered to be related to venetoclax.

There may be risks if venetoclax is used with other medications. Consult your Study Team before taking any additional medications during this study. Talk with your doctor before getting any vaccines during this study. Use of venetoclax may raise the chances of an infection or make the vaccine not work as well. Ibrutinib. The following side effects (adverse events) were reported in people receiving ibrutinib. Most Common Side Effects of the Study Drug Ibrutinib (these side effects occurred in at least 1 in every 5 people taking ibrutinib, 20% or **more)**
Muscle and joint pain (musculoskeletal pain)  
Low white blood cell count (WBC, blood cells that help fight infection)
(neutropenia)
Bruises Rash Upset stomach (nausea)
Increase in frequency of diarrhea (loose or watery stools)
Less-likely Side Effects (these side effects occurred in at least 1 in every 10 people taking ibrutinib; 10% or **more)**
Common cold (upper respiratory tract infection)  
Lung infection (pneumonia)
Sores in the mouth (stomatitis)
Sinus infection (sinusitis)
Skin infection Fever (pyrexia)
Low platelet count (cells that help blood to clot) (thrombocytopenia)
High blood pressure (hypertension)
Headache Joint aches (arthralgia)
Vomiting Constipation  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Swelling of the hands or feet (peripheral edema)
Muscle spasms

There may be risks if ibrutinib is used with other medications. Consult your Study Team before taking any additional medications during this study. Talk with your doctor before getting any vaccines during this study. Use of ibrutinib may raise the chances of an infection or make the vaccine not work as well.

Non-melanoma skin cancer, such as basal cell carcinoma (BCC) or squamous cell carcinoma Severe infection throughout the body (sepsis) Inflammation within the lungs that may lead to permanent damage
(Interstitial lung disease)
Abnormal heart rhythm (atrial fibrillation)
Urinary tract infection (UTI)
Increased level of uric acid in the blood (hyperuricemia) Dizziness Nose bleed (epistaxis)
Small red or purple spots caused by bleeding under the skin (petechiae) Low white blood cell count (WBC, blood cells that help fight infection) with fever
(febrile neutropenia)
Increase in WBC counts (leukocytosis)
Increase in lymphocyte (a type of WBC) count (lymphocytosis)
Blurry vision Skin redness (erythema)
Fingernails or toenails breaking (onychoclasis)
Rare Side Effects (these side effects occurred in less than 1 in every 100 **people**

High levels of cancer cell breakdown products, which may lead to changes in kidney function, abnormal heartbeat, or seizures (tumor lysis syndrome)
Bleeding around the brain (subdural hematoma)
Liver failure (hepatic failure)
High WBC count with abnormal clumping that can lead to bleeding
(leukostasis syndrome)
Inflammation of the fatty tissue underneath the skin (panniculitis) Severe rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
Swollen face, lip, mouth, tongue or throat (angioedema)
Itchy rash (urticaria)  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Abnormal rapid and/or irregular heart rhythm that starts from the lower chambers
(ventricles) of the heart (Ventricular tachyarrhythmia)

Most of these side effects listed above have been mild to moderate in severity; however severe side effects have occurred. Some side effects have been severe enough to lead to study drug discontinuation, dose modification or reduction, hospitalization, disability, and sometimes death. If any of the events below happen, contact your Study Doctor **immediately** to help prevent the event from getting worse. If the event gets worse or you are in distress, CALL 911. Your study doctor may also choose to stop ibrutinib for a short time or reduce its dose to allow you to recover from any side effects.

Abnormal heartbeats (atrial fibrillation; atrial flutter; and/or ventricular tachyarrhythmia) ) have been reported in patients treated with ibrutinib especially when they also have had heart conditions; increased blood pressure; infections; or an abnormal heartbeat in the past. The heartbeat may be fast or irregular causing symptoms such as a pounding or racing heart; chest discomfort; shortness of breath; dizziness; fainting; feeling light-headed; and/or weakness. You should seek medical attention and notify your Study Doctor **immediately** if you develop any of these symptoms while receiving the study drug.

Interstitial lung disease is a group of lung disorders in which the tissues become inflamed and may become damaged. Interstitial lung disease is not associated with infections (eg, bacteria, viruses, fungi) and has been reported in patients treated with ibrutinib. You should report to your physician if you have cough; or any signs of new or worsening respiratory symptoms, such as shortness of breath or difficulty breathing.  
Notify your Study Doctor **immediately**, as these symptoms could also be due to other events, such as heart problems (see above).

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells has occurred with venetoclax treatment, most often right after starting treatment, or if the patient has a large or extensive cancer. The levels of breakdown products in your blood may cause changes in kidney function, abnormal heartbeat, or seizures. This is called tumor lysis syndrome (TLS). Your Study Doctor will give you a medication to reduce the chance of TLS, but may still do blood tests to check for TLS.

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have happened during treatment of cancer and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your study doctor may do blood tests to check for TLS.

Tumor lysis syndrome (TLS), discussed above, may occur with ibrutinib treatment, and may cause changes in kidney function, abnormal heartbeat, or seizures. Your Study Doctor may do blood tests to check for TLS.

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma of the skin) have been reported with more frequency and may be related to the use of ibrutinib. Other cancers have been reported such as solid tumors and blood cancers,  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia but their relationship to the use of ibrutinib is unknown. You should tell your study doctor if you develop a new cancer while in the study.

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma of the skin) have been reported with more frequency and maybe related to the use of ibrutinib. Other cancers have been reported such as solid tumors and blood cancers, the relationship to the use of ibrutinib is unknown. You should tell your Study Doctor if you develop a new cancer while in the study.

Hypertension is also called high blood pressure, and has been commonly reported in subjects treated with ibrutinib. Sometimes, people with high blood pressure may have headaches, dizziness, nervousness, sweating, difficulty in sleeping, facial flushing or nosebleeds, but in some cases, there may be no symptoms and it may go undetected. After starting ibrutinib, your doctor may measure your blood pressure regularly. You should let your study doctor know if you have any of the symptoms of high blood pressure which may mean that you have developed hypertension or that your hypertension is getting worse. Your study doctor may adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.

You may experience viral, bacterial, or fungal infections during treatment with ibrutinib. Some of these infections have been associated with hospitalization and death. Contact your Study Doctor **immediately** if you have fever; chills; weakness; confusion; body aches; cold or flu symptoms; vomiting; jaundice; feel tired; or feel short of breath. These could be signs of a serious infection. Your study doctor may start or continue medication to help prevent or treat an infection. A rare and usually fatal viral disease in the brain, progressive multifocal leukoencephalopathy (PML), has been reported in patients treated with ibrutinib in combination with rituximab and in patients who were previously treated with rituximab. If you experience symptoms such as weakness, paralysis, vision loss and/or impaired speech, you should seek medical attention **immediately** and also tell your Study Doctor.

You may experience bruising or bleeding during treatment with ibrutinib. Rarely, serious or fatal internal bleeding may occur, such as bleeding in your stomach, in your intestine, or in or around your brain, sometimes resulting in death. If you take other medicines or supplements that increase your risk of bleeding (such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) or medicines used to prevent or treat blood clots or stroke) ibrutinib may increase this risk. Blood thinners such as warfarin or other vitamin K antagonists should not be taken together with ibrutinib. Supplements such as fish oil and vitamin E preparations should be avoided while taking ibrutinib. Seek medical attention **immediately** and also call your Study Doctor if you have signs or symptoms of severe bleeding in or around the brain such as sudden severe headaches; weakness in the arms or legs; difficulty speaking or understanding speech; or loss of balance. You should also seek medical attention immediately and notify your Study Doctor if you have signs or symptoms of serious  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia bleeding, such as blood in your stools or urine or bleeding that lasts for a long time or that you cannot control.

You may experience an increase in the number of lymphocytes, which is a type of white blood cell, in your blood (lymphocytosis). This may occur in the first few weeks of treatment and you should not assume that this increase in white blood cells means that your disease is worsening. This increase may last for several weeks to months. Increased number of white blood cells in your bloodstream may change the blood flow, resulting in bleeding or clotting (leukostasis). Isolated cases of these events have been reported in patients treated with ibrutinib. Your Study Doctor will monitor your blood counts and may administer additional therapy as needed. Talk to your Study Doctor about what your test results mean.

Severe decreases in white blood cells, red blood cells, and platelets (neutropenia, anemia, and thrombocytopenia) were reported in subjects treated with ibrutinib. If you experience symptoms such as fever; weakness; or easy bruising and/or bleeding; you should tell your Study Doctor **immediately** and seek medical attention.

Rare cases of liver failure have been reported in patients treated with ibrutinib. Symptoms of liver failure include yellowing of the eyes and skin (jaundice), itching of the skin, dark-colored urine; gray- or clay-colored bowel movement (stools); confusion; upset stomach (nausea), loss of appetite; tiredness (fatigue); or diarrhea. You should tell your Study Doctor **immediately** if you have any of these symptoms which may suggest liver disease. Your Study Doctor may be able to diagnose and provide you required medical care.

Sometimes people have allergic reactions to drugs. Serious allergic reactions can be life-threatening. If you have an allergic reaction to the study drugs, you might develop a rash; difficulty breathing; wheezing when you breathe; sudden low blood pressure with light-headedness; swelling around the mouth, throat or eyes; a racing heartbeat; and/or abnormal or increased sweating. Before starting the study drug, you must tell your Study Doctor about any drug allergies. You should tell the Study Doctor **immediately** if you have any allergy symptoms listed above.

A maculopapular rash (flat, red areas on the skin with small bumps) has been commonly reported in patients treated with ibrutinib alone or in combination with other drugs. Most rashes are mild to moderate in severity and begin 2 to 3 weeks or longer after starting ibrutinib.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia There have been rare reports of severe skin reactions (known as severe cutaneous adverse reaction or "SCAR," involving more than 50% of the body), and/or rash with blisters and peeling skin, which may include open ulcers or sores in the mouth and other areas of the body (Stevens-Johnson Syndrome). These skin rashes could be life-threatening. You should notify your Study Doctor **immediately** if you develop a rash that spreads quickly, or if you notice peeling of your skin, with or without ulcers or sores in your mouth.

Some juices or foods like grapefruit and Seville oranges, as well as some medications, may interfere with the way your body processes ibrutinib. This interference could cause the amount of ibrutinib in your body to be higher or lower than expected. It is also possible that taking the study drug with your regular medications or supplements, including fish oil, Vitamin E, or other vitamins, may change how your regular medications, or your regular supplements, work. It is very important that you avoid grapefruit juice and Seville oranges and tell the Study Doctor about all medications, supplements, or herbal medicine like St John's wort that you are taking during the study. You should notify your Study Doctor **immediately** about any side effects to avoid possible harm.

You may experience an increase in the number of lymphocytes, which is a type of white blood cell, in your blood (lymphocytosis). This may occur in the first few weeks of treatment and you should not assume that this increase in white blood cells means that your disease is worsening. This increase may last for several weeks to months. Increased number of white blood cells in your bloodstream may change the blood flow resulting in bleeding or clotting (leukostasis). Isolated cases of these events have been reported in patients treated with ibrutinib. It is not clear whether ibrutinib will increase the number of total white blood cells in the blood, not just the lymphocytes. This is something the Study Team will be looking out for. Your Study Doctor will monitor your blood counts and may administer additional therapy as needed. Talk to your Study Doctor about what your test results mean.

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells has occurred with venetoclax treatment, most often right after starting treatment, or if the patient has a large or extensive cancer. The levels of breakdown products in your blood may cause changes in kidney function, abnormal heartbeat, or seizures. This is called tumor lysis syndrome (TLS). Your Study Doctor will give you a medication to reduce the chance of TLS, but may still do blood tests to check for TLS.

Unusual levels of chemicals in the blood caused by the fast breakdown of cancer cells have happened during treatment of cancer and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your study doctor may do blood tests to check for TLS.

Tumor lysis syndrome (TLS), discussed above, may occur with ibrutinib treatment, and may cause changes in kidney function, abnormal heartbeat, or seizures. Your Study Doctor may do blood tests to check for TLS.

High blood pressure, also called hypertension, has been commonly-reported in subjects treated with ibrutinib. Sometimes people with high blood pressure may have headaches; dizziness; nervousness; sweating; difficulty in sleeping; facial flushing or  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia nosebleeds; but in some cases, there may be no symptoms and it may go undetected.  
After starting ibrutinib, your doctor may measure your blood pressure regularly. You should let your Study Doctor know if you have any of the symptoms of high blood pressure, which may mean that you have developed hypertension or that your hypertension is getting worse. Your Study Doctor may adjust existing anti-hypertensive medications and/or start anti-hypertensive therapy as appropriate.

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma of the skin) have been reported with more frequency and may be related to the use of ibrutinib. Other cancers have been reported such as solid tumors and blood cancers,  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia but their relationship to the use of ibrutinib is unknown. You should tell your study doctor if you develop a new cancer while in the study.

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma of the skin) have been reported with more frequency and maybe related to the use of ibrutinib. Other cancers have been reported such as solid tumors and blood cancers, the relationship to the use of ibrutinib is unknown. You should tell your Study Doctor if you develop a new cancer while in the study.

There may be risks if venetoclax is used with other medications. Consult your Study Team before taking any additional medications during this study. Talk with your doctor before getting any vaccines during this study. Use of venetoclax may raise the chances of an infection or make the vaccine not work as well. Ibrutinib. The following side effects (adverse events) were reported in people receiving ibrutinib. Most Common Side Effects of the Study Drug Ibrutinib (these side effects occurred in at least 1 in every 5 people taking ibrutinib, 20% or **more)**
Muscle and joint pain (musculoskeletal pain)  
Low white blood cell count (WBC, blood cells that help fight infection)
(neutropenia)
Bruises Rash Upset stomach (nausea)
Increase in frequency of diarrhea (loose or watery stools)
Less-likely Side Effects (these side effects occurred in at least 1 in every 10 people taking ibrutinib; 10% or **more)**
Common cold (upper respiratory tract infection)  
Lung infection (pneumonia)
Sores in the mouth (stomatitis)
Sinus infection (sinusitis)
Skin infection Fever (pyrexia)
Low platelet count (cells that help blood to clot) (thrombocytopenia)
High blood pressure (hypertension)
Headache Joint aches (arthralgia)
Vomiting Constipation  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Swelling of the hands or feet (peripheral edema)
Muscle spasms

There may be risks if ibrutinib is used with other medications. Consult your Study Team before taking any additional medications during this study. Talk with your doctor before getting any vaccines during this study. Use of ibrutinib may raise the chances of an infection or make the vaccine not work as well.

The effects and safety of ibrutinib as maintenance therapy is unknown. You may have all, some, or none of the listed side effects of ibrutinib. Please tell the Study Doctor or study staff right away if you have any side effects. Please tell them if you have any other problems with your health or the way you feel during the study, whether or not you think they are related to the study drug. Your Study Doctors and nurses will check you closely for side effects. You may receive medicines or other treatments to prevent or reduce some of these effects. In addition to the risks listed above, there could be unknown or unexpected side effects associated with the use of ibrutinib. You will be told in a timely manner, verbally and in writing, of any new information, findings, or changes to the way the research will be done that might influence your willingness to continue your participation in this study.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia You should get medical help and contact the Study Doctor or study staff if you have any of these or any other side effects during the study. In addition, there are other risks and possible discomforts you might experience from the study procedures. The following discusses procedure risks related only to the research, and does not include risks of procedures that should be discussed as part of your regular medical care.  
Blood draws: A blood draw may cause fainting; inflammation of the vein; stinging, discomfort, or pain; bruising; discomfort; redness; burning; or bleeding at the site where the needle is placed to draw the blood. There is a slight chance of infection. You may feel dizzy or you may faint. If you feel faint, you should immediately lie down to avoid falling ECG: Risks from an ECG can include skin irritation and/or a rash from the gel, or from wearing or removing the patches.  
MRI: The very strong magnetic fields of the MRI machine do not cause generally cause harmful effects at the levels used in the machine. However, there are some important considerations. The magnet will attract or even move some metals and affect or damage some electronic devices. Exposure of the following to MRI magnetic fields may cause harm to you or others.  
o Artificial heart valve; a pacemaker; or any other biomedical device in or on your body. These devices could malfunction when exposed to the very strong magnetic field.  
o Metal plate; pin; screws; surgical clips; metallic fragments; or any other metallic implant in your body. These pieces of metal could move while in your body, causing possible serious injury or death.  
In addition, when you are in the MRI scanner, you may experience discomfort or anxiety due to the small amount of space inside the machine, or from the loud noises the MRI scanner makes. You may receive a medication to calm you if you need help with this.
If you have a history of severe allergies (eg, bee-sting reaction, food, shellfish, or nut reactions), or have previously had a reaction to medications or contrast agents, in particular, Gadolinium-based contrast agents, you may be at risk of a serious reaction, which can be severe and/or life-threatening, including breathing difficulty; sweating; numbness; or heart palpitations. Tell the study team or technician immediately **if you experience these.**  
Radiologic imaging: X-ray / CT scans. A CT scan exposes you to radiation
(discussed below). When you are in the scanner, you may experience discomfort or anxiety due to be in the small amount of space inside the machine, or from the loud noises the scanner makes. If you become anxious or concerned in tight spaces, or from loud noises, tell the study team or technician before the scan. You may receive a medication to calm you if you need help with this.  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia  
Bone marrow biopsy: The most common side effects, which are usually minor, include pain; discomfort; bleeding; swelling; scarring; bruising; infection; and fever. In extremely rare cases, an allergic reaction to the local anesthetic used to numb the biopsy site can occur. This is a routine procedure, and established institutional procedures will be followed.  
Pregnancy / Reproductive Risk: There may be known or unknown risks to a fetus
(unborn child) or the pregnant woman, even if it is the man participating in this study. The effects of ibrutinib on a developing fetus or a child are also unknown; therefore women who are pregnant or nursing are not allowed to be in this study.  
Nobody knows what these risks are right now. Some of these drugs cause women to have premature (early) delivery, or to have a child with birth defects. There is a risk that pregnancy could still result despite the responsible use of reliable method of birth control. Detailed information about preventing pregnancy is given elsewhere in this document.  
Women of childbearing potential: If you believe you might be pregnant, or even if you experience a menses cycle ("have your period"), you must inform the Protocol Director or study team immediately.  
Breast-feeding: It is not known whether ibrutinib or its metabolites are excreted in human milk. Nobody knows what these risks are right now. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ibrutinib, breast-feeding should be discontinued during ibrutinib treatment.  
Genetic research risks: This research involves genetic studies and information.  
Procedures have been put into place that are designed to make it very difficult for the results from genetic research to be linked to you. However, even without your name or other identifiers, your genetic information is unique to you, and there is a remote possibility that someone could trace the information in a central database back, and identify you. There is a remote possibility information from your participation in this study could adversely affect you or your family in some way if a genetic disorder were discovered.  
Personal anxiety: Following are some common concerns that research subjects may have.  
o You may be asked sensitive or private questions which you normally do not discuss. It may be necessary to answer some of these questions related to your health and medical status.  
o You may feel embarrassed during the physical exam. You may request that the physical exam be done by a clinician of the same gender.  
o You may be concerned about your personal information being revealed.  
Although the Study Team; the IRB; and FDA do their best to protect your personal information, this cannot be absolutely guaranteed.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia  
Other risks: Since venetoclax and ibrutinib are investigational when taken in combination, there may be other risks that are unknown ("unforeseeable") at this time.  
You may experience some inconvenience due to the schedule and length of Study Visits. Your doctor may require that you remain in the clinic until very late in the day or that you even stay overnight in order to comply with the requested blood sampling schedule on some of the pharmacokinetic (PK) days.
It is important that you report all symptoms and side effects **that you experience** as soon as **they occur, whether or not you think they are caused by the** Study Drug. Contact the Study Team at (650) 725-4041 **or via the Nurse** Coordinators at (650) 498-6000 (24 hour **number).** If you are unable to reach anyone at the number(s) listed above, and you feel you may need medical attention, call 911 or go to the nearest emergency room.
Clinical trial: NCT03045328
Section: Procedures
Subsections: Procedures|Study Follow-Up Procedures

It may be harmful to enter this study while receiving some medications, therefore, you may need to stop taking certain medications. Your Study Doctor will review your medications and provide you with specific instructions. Before you begin the study, you will need to have certain medical examinations, tests, or procedures to find out if you can be in the study. This is called "screening." Some of  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia these examinations, tests, or procedures may be part of your regular medical care, and/or and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. Before you join this study, the Protocol Director Steven E. Coutre, MD and/or the research study staff will review this document with you, and ask you to sign this informed consent document. After you have signed this document, and received a signed copy, the study will begin with a screening visit.

As part of your regular medical care, the study team would like to follow-up with you about every 3 months after you finish study treatment. The following tests and procedures/assessments will be conducted.  
  
Approval Date: November 14, 2018 Expiration Date: November 14, 2019
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Medical **history**: as described above.  
Physical examination: as described above. Blood collection: Blood will be collected as described above, for hematology; blood chemistry; and cancer mutation testing. About 3 tablespoons (45 mL) will be collected. Adverse event monitoring: as described above. Disease Status / Cancer Assessment: As described above, but without CT or MRI scan or bone marrow biopsy unless medically justified. If necessary, the study team may ask you to return to the center for additional study tests ("follow-up tests") to clarify or confirm data already generated in the study. Throughout the study, you will be told the results of tests that are part of your clinical care, but you may not be told the results of the tests for research purposes only, including the genetic tests and any future research tests. Location: The location of the Study Follow-Up Visit will be at the Study Clinic and the Stanford medical imaging locations, as described above.
Clinical trial: NCT03045328
Section: Purpose of Research
Subsections: Purpose Of Research

The proposed study investigates the use of venetoclax in combination with a standard dose of ibrutinib, as a treatment for CLL or SLL. The proposed study is called a "Phase 2" study. The study team hopes to learn if the combination of venetoclax and ibrutinib is safe and effective to treat CLL or SLL. Venetoclax, as Venclexta, has been approved by FDA for the treatment of patients with CLL who have a genetic mutation called "17p deletion;" after at least one prior therapy. Ibrutinib, as Imbruvica, has been approved by FDA for the treatment of CLL regardless of the presence or absence of the 17p deletion, and also to treat mantle cell lymphoma (MCL) after one prior therapy; relapsed or refractory marginal zone lymphoma (MZL); chronic graft-vs-host disease (GvHD); or Waldenström's macroglobulinemia (WM). Both drugs are being studied in other various disease settings. The combination of venetoclax + ibrutinib is being used in this study under a study protocol submitted to FDA, in an Investigational New Drug application (IND). Although both drugs are approved by FDA, the drugs continue to be studied in several cancer settings, including both CLL and SLL.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Your normal medical care, or the "Standard of Care," for CLL or SLL could include ibrutinib alone, or venetoclax if you have the 17p deletion, as well as allogeneic stem cell transplantation, chemotherapeutic agents; and/or monoclonal antibodies, as well as allogeneic hematopoietic cell transplantation (eg, bone marrow transplant). Some of these alternatives may not be right for you. Your doctor will discuss the specifics of your case with you. Your normal medical care would also include medical exams and blood tests, and medical scans to check the status of your cancer such as computed tomography (CT) or magnetic resonance imaging MRI scans. The use of venetoclax in this research study is investigational ("experimental"). The word "investigational" means that venetoclax is not approved by the FDA for use in the United States to treat CLL that does not have the 17p deletion, or to treat SLL. This study is being conducted under an application submitted to FDA, called an "Investigational New Drug Application" or "IND." Venetoclax will be provided by the drug manufacturer AbbVie Inc. Ibrutinib will be provided by the drug manufacturer Pharmacyclics LLC. The other parts of this study that are research (not part of your regular care) are the  
The collection of blood samples for determinations of drug levels in the blood Blood collection for genetic testing before treatment at Week 1 Day 1, and at the Final Study Visit or time of relapse.
If you decide to terminate your participation in this study, you should notify Dr Coutre at 650-823-0828. This research study is looking for 20 people with CLL or SLL. The study is being done at 2 research sites, Stanford University and City of Hope in Duarte, CA. Stanford University expects to enroll and treat about 15 research study participants. This study is being paid for by Pharmacyclics LLC. Study drugs are being provided by Pharmacyclics and AbbVie, Inc.
Clinical trial: NCT03045328
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this study is entirely voluntary. Your decision not to participate will not have any negative effect on you or your medical care. You can decide to participate now, but withdraw your consent later and stop being in the study without any loss of benefits or medical care to which you are entitled. You will be informed of any significant new information about this study or the study drugs venetoclax and ibrutinib that might affect your willingness to participate in this research study. You will be told the results of tests that are part of your medical care, but you may not be told the results of the research tests, including any future research tests.  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia
Clinical trial: NCT03045328
Section: Withdrawal from Study
Subsections: Treatment Discontinuation|Withdrawal From The Study

At the time that it is decided you should conclude treatment in this study, you will have a final study visit, and the following tests and procedures/assessments will be performed: Medical **history**: as described above. Physical examination: as described above. Blood collection: Blood will be collected as described above, for hematology; CLL blood test; and cancer mutation testing. About 1 tablespoon (15 mL) will be collected. Disease Status / Cancer Assessment: As described above, with CT or MRI scan. Electrocardiogram **(ECG)**: As described above, if the Study Doctor feels it is necessary to evaluate your current medical condition. Adverse event monitoring: as described above. Location: The location of the Study Visits will be at the Study Clinic and the Stanford medical imaging locations, as described above. End-of-Treatment (about 30 days after last dose) When you are finished taking the Study Drugs, you will have the following tests and procedures/assessments. Medical **history**: as described above. Physical examination: as described above. Blood collection: Blood will be collected as described above, for hematology; blood chemistry; and cancer mutation testing. About 3 tablespoons (45 mL) will be collected. Electrocardiogram **(ECG)**: As described above, if the Study Doctor feels it is necessary to evaluate your current medical condition. Location: The location of the End-of-Treatment Visit will be at Study Clinic and the Stanford medical imaging locations, as described above.

If you first agree to participate and then you change your mind, you are free to withdraw your consent and discontinue your participation at any time. Your decision will not affect your ability to receive medical care for your disease and you will not lose any benefits to which you would otherwise be entitled. If you decide to withdraw your consent to participate in this study, you should notify Steven E Coutre, MD at 650-823-0828. To help you safely finish your participation in the study, the Study Doctors may ask you to have more tests and you will be asked to come into the clinic for an End-of-Treatment Visit after stopping the Study Drug. The Study Doctor will discuss your treatment options with you at this time. If your participation in the study is ended, you must return all study-related supplies, including unused Study Drug.  
  
  
E.  MD Protocol Title: An Open-Label Trial of Venetoclax with Ibrutinib in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia If you withdraw from the study, or the study medication is stopped for any reason,  
Your cancer may get worse.  
To help you leave the study safely, the Study Doctors may ask you to have more tests.  
The Study Doctors may also ask if you wish to take part in the follow-up portion of the study. If you agree to continue with the follow-up portion of the study, information about your health will continue to be collected as described above in the Follow-up Procedures section.  
The Study Doctor will discuss with you the different withdrawal decisions, including your options for continued treatment.  
If your participation in the study ends, you must return all study-related supplies, including unused Study Drug.  
Data and information from your participation may not be removed from the research study database and may continue to be used to complete the research analysis. This is discussed in more detail under the heading "Authorization To Use Your Health Information For Research Purposes" on the following pages.
The Protocol Director may also withdraw you from the study and the study medications may be stopped, without your consent for one or more of the following reasons:
Failure to follow the instructions of the Protocol Director and study staff.  
The Protocol Director decides that continuing your participation could be harmful to you.  
If your tumor worsens (tumor progression).  
If you have serious side effects during treatment with Study Drug.  
You have become pregnant.  
You need treatment not allowed in the study.  
The study is stopped by the drug manufacturer; the Study Doctor; the Stanford Institutional Review Board (the IRB, a group of people who review the research to protect your rights), or by a regulatory agency such as the US FDA.  
Other administrative reasons.  
Unanticipated circumstances.