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The RESONATETM-2 (PCYC-1115-CA) Clinical Trial A resource guide for patients and their families The purpose of this study is to test whether or not the investigational (experimental) study drug (ibrutinib, also known as "PCI-32765") works and is safe in patients with CLL / SLL. It compares ibrutinib to the FDA-approved drug chlorambucil. This study is being conducted in patients who are age 65 or older, who have not received prior treatment for their CLL / SLL. The number of visits wil depend on the duration of your This study is expected to last about 3 years. The length of time that you take part in this study depends on how wel your cancer responds to the study treatment. It also depends on the side effects you might have because of the study treatment. You may be reimbursed for reasonable transportation costs for travelling to and from the clinic. Please ask your study doctor if Have your health care professional call 1-855-IBRUTINIB (1-855-427-8846), or e-mail for more information on research center locations near you. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
• A clinical trial is a study in which doctors learn about potential new medicines and • The goal of a clinical trial is to learn if a medicine works and is safe in certain people by studying those people under carefully managed conditions. • In a clinical trial, a potential new medicine is often compared with an approved drug to test if it is useful for that particular disease. • The RESONATETM-2 clinical research trial is a trial to learn how a potential new medicine, ibrutinib (PCI-32765), affects people who have been diagnosed with B-cel chronic lymphocytic leukemia, or CLL. This study is being done in patients who are age 65 or older, and who have not received prior treatment for their CLL. • Patients will either receive ibrutinib, or the FDA-approved drug chlorambucil, and the activity and safety will be compared in patients treated with the two agents. • The purpose of this study is to find out and compare: o How wel the study treatments control CLL o How the CLL cel s respond to the study treatments o The side effects of the study treatments o How long the study drugs stay in the blood • Chlorambucil is approved by the FDA and certain other global health authorities for RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
How does the RESONATETM-2 (PCYC-1115-CA) study work? • About 272 patients around the world wil take part in this study. • Patients who take part in the RESONATETM-2 study will be randomly assigned by a computer to one of two groups. Al patients wil have an equal chance of being placed in either group: o Patients in Treatment Group A will receive chlorambucil o Patients in Treatment Group B will receive ibrutinib • All patients who take part in the RESONATETM-2 study will be closely monitored by the study doctor at least once a month to see if their disease is getting worse. • If you choose to take part in the RESONATETM-2 study, the medicines will be provided to • As long as you agree to continue to receive the medicine, you wil need to come to the study center for al of the visits required for the study. At these visits, your study doctor will examine you and you wil be given enough of medicine to last until your next You wil also be invited to participate in the extension study (PCYC-1116-CA) if your cancer gets worse. This study wil al ow you to receive alternative treatments. • If you do not do wel on the medicine and your cancer gets worse, the medicine will be stopped and you wil have the chance to be in an extension study, PCYC-1116-CA, if you • Your doctor may offer to put you on other treatments that might work to improve the cancer. If you received chlorambucil (Treatment Group A), one of the choices offered may be the study drug ibrutinib, if you meet certain criteria. If you received ibrutinib (Treatment Group B), other treatments, either approved or other study drugs, may be RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
Am I eligible to participate in the RESONATETM-2 study? You may be eligible to participate in the RESONATETM-2 study if you: • Are age 65 years or older. • Have been diagnosed with B-cell CLL and have disease that requires treatment. • Have NOT received any other treatment for your B-cel CLL. • Meet certain diagnostic testing and laboratory criteria. • Are willing to come to the study center for al of the required visits. Can I change my mind if I no longer want to participate? • You may choose not to take part in this study and that decision wil not affect your • If you decide to take part in the study, you can stop participating at any time and your decision will not affect your access to medical care in the future. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
As long as you agree to continue to receive the medicine, you wil need to come to the study center for all of the visits required for the study. At these visits, your study doctor will examine you and you wil be given enough of medicine to last until your next scheduled visit. o You will receive up to a maximum of 24 doses of chlorambucil as a pil by mouth. o You will take chlorambucil on Day 1 and Day 15 of every month, up to a  Day 1 and Day 15 of Month 1 at the clinic  Day 1 and Day 15 of Month 2 at the clinic  For Months 3 – 12, Day 1 at the clinic, and Day 15 at home o You will start with a dose of 0.5 mg/kg of body weight. Your doctor may increase the dose by 0.1 mg/kg at subsequent months, up to a dose of 0.8 mg/kg. This means your study coordinator will calculate the dosage based on your current weight and determine the number of tablets you wil need to take every month. You wil be given bottles of study drug to take home with you. o You wil take 420 mg of the study drug by mouth each day. This is three 140 mg capsules that are to be taken with 8 ounces (240 mL) of water. o Ibrutinib should be taken at least 30 minutes before eating or at least 2 hours after eating. You should take ibrutinib at around the same time each day. The capsules must be swallowed whole. If you have a hard time swallowing capsules or pil s, you should not be in this study. Your doctor may suggest that you take additional drugs before taking the study drug to avoid side effects, such as o At each visit, you will be given at least enough ibrutinib to last until your next visit. You will take ibrutinib at home except on the days when you come to have o You may continue to receive ibrutinib until your disease gets worse or until you RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
• Chlorambucil is in a class of drugs called alkylating agents. This type of drug works by • Chlorambucil is approved by the FDA and certain other global health authorities for treating and is included in US national and European treatment guidelines as a drug that can be used for the initial treatment of older patients with CLL. What are the risks associated with taking chlorambucil? As with any other cancer treatment, there may be side effects or risks associated with taking chlorambucil. The most common serious side effects seen in CLL patients taking chlorambucil (1 or more occurrences in every 3 – 30 patients) were: • Neutropenia (low white blood cells, these are the cells that help fight infection) • Anemia (low red blood cells) • Thrombocytopenia (low platelets, these are the cells that help your blood clot) Additional common side effects (1 or more occurrences in every 3-5 patients) were: If you decide to participate in the RESONATETM-2 clinical research trial, your doctor will closely watch for side effects. Your doctor may be able to give you medications to help treat the side effects or keep them from becoming worse. Your study doctor may also choose to stop the chlorambucil for a short time to allow you to get better from any side effects. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
• Ibrutinib is in a class of drugs called kinase inhibitors. Kinases are proteins inside cells that help cells live and grow. Ibrutinib is believed to block a kinase that helps blood cancer cells live and grow. By blocking this kinase, it is possible that the cancer cells may die or stop growing. • Ibrutinib is also being tested in other studies in patients who have other blood cancers. Over 550 patients have received the study drug in six clinical studies sponsored by Pharmacyclics, Inc., including more than 250 patients with CLL or SLL. • Ibrutinib is an experimental drug that is currently being tested and is not approved by the U.S. Food and Drug Administration (FDA) or any other global health authorities. What are the risks associated with taking ibrutinib? Your study doctor wil discuss with you the side effects that have been seen with ibrutinib. The most common side effects seen (1 or more occurrences in every 3 – 4 patients) were: Less common side effects (1 or more occurrences in every 5-7 patients) include: • Peripheral edema (swelling of the hand or feet) • Upper respiratory infection (a cold) If you decide to participate in the RESONATETM-2 study, your doctor will closely watch for side effects. Your doctor may be able to give you medications to help treat the side effects or keep them from becoming worse. Your study doctor may also choose to stop the ibrutinib for a short time to al ow you to get better from any side effects. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
RESONATETM-2 Clinical Trial: Screening Assessment You will be checked to see if you are able to be part of the study • If you are interested in participating in the RESONATETM-2 study, you will be evaluated to determine if you are able to be part of this study. • Screening tests will be done within 28 days before getting your first dose of medicine. o You will be asked about your medical history and your medical chart will be reviewed to o You will be asked to complete questionnaires about how you are feeling and your overall health (these may be cal ed Quality of Life questionnaires). o You will be asked about medications and herbs you might be currently taking, you will have a physical exam done, vital signs will be taken, and an electrocardiogram (ECG, a recording of the electrical activity of the heart) will be done to check your heart. o Routine blood tests wil be done to check your blood counts (numbers of each type of blood cell), chemistries (elements and minerals in your blood), how well your blood clots, for hepatitis, how wel your organs are functioning and there may be other tests done to look at your cancer cells to determine how they may respond to treatment. o You wil have a CT scan of your neck, chest, abdomen, and pelvis so your doctor can o You will have some of your bone marrow taken to check on your cancer or to determine your exact type of blood cancer (if you haven’t had one done already). In any event, you wil need one within 90 days before your start in this study. If you are able to be in the study, you will be asked to sign an informed consent form and that will mean you are “enrolled” in the study. You wil start your study treatment within 28 days of completing the required procedures. You o Your study doctor tells you that your cancer has gotten worse. o You have a side effect that may put your health at risk. o You decide that you do not want to be in this study anymore. o Your doctor decides to stop the treatment if he/she feels it is in your best interest. o The drug company conducting the study decides to stop or interrupt the study. o You do not comply with study treatment, visits and /or study procedures. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
RESONATETM-2 Clinical Trial: Schedule of Visits The schedule of assessment may occur as fol ows:  You will be asked to complete questionnaires about how you are feeling and your overall health, also called Quality of Life questionnaires, before you see  You will have a physical examination and your vital signs wil be checked.  You wil be asked about any side effects you may be experiencing as well as  The study site staff wil complete a form to rate how your body parts are  Blood wil be taken for routine tests and other tests to look at your cancer cel s and how they may be responding to treatment.  If you are receiving ibrutinib, blood samples may be taken at various times to find out how much drug is in your blood and how your body handles the drug. Screening
Treatment Phase
Fol ow up Phase
Study Drug Administration
ARM Chlormabucil
ARM Ibrutinib
* Day 15 visits during Months 1 through 7 only RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.
Resources Where can I learn more about CLL? Where can I learn more about clinical trials? The RESONATETM-2 (PCYC-1115-CA) Clinical Research Trial is organized and funded by For more information about the RESONATETM-2 (PCYC-1115-CA) Clinical Research Trial, call 1-855-IBRUTINIB (1-855-427-8846), mail [email protected] or contact your doctor. RESONATETM-2 Patient Brochure 30-APR 2013

The information provided herein may contain references to ibrutinib or a use of ibrutinib which has not been approved by any regulatory
agency. Providing this information should not be construed as recommending the use of ibrutinib for uses which have not been approved by
any regulatory agency. The safety and efficacy of the investigational use of ibrutinib has not been determined. There is no guarantee that
the investigational uses listed wil be filed with and/or approved for marketing by any regulatory agency. For additional information, you
may visor products approved by any regulatory agency please consult the product’s ful prescribing information
for a complete discussion of risks and benefits of the product for its approved indications.

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