Clinical trial: NCT01399372
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study? Your Other Choices May Include:

Reproductive risks: You should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while on this study. It is important you understand that you need to use birth control while on this study. Check with your study doctor about what kind of birth control methods to use and how long to use them. Some methods might not be approved for use in this study. . A pregnancy test will be required if you are a woman of childbearing potential.  
For more information about risks and side effects, ask your study doctor.
Clinical trial: NCT01399372
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private? (4/17/14)

Data are housed at NRG Oncology Statistics and Data Management Center in a password-protected database.  
We will do our best to make sure that the personal information in your medical record will be kept private.
Clinical trial: NCT01399372
Section: Duration of Study Involvement
Subsections: Before You Begin The Study …|When You Are Finished Taking All Of The Chemotherapy…(1/27/15)|How Long Will I Be In The Study?

You will need to have the following exams, tests or procedures to find out if you can be in the study. These exams, tests or procedures are part of regular cancer care 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. This will be up to your study doctor.  
- MRI of your brain - CT scan of your chest, abdomen, and pelvis - History and physical examination - Blood tests for bone marrow function, liver function, and renal function - HIV test - Pregnancy test (if are a woman of childbearing potential)
In addition, when you enter the study, you will need to agree to permit your doctors to send the block of tumor tissue obtained at the time of your brain tumor surgery to a central pathology site. There, a pathologist will confirm that the tumor is the type of tumor being studied in this trial.

When you are finished with the treatment, you will need to come back to clinic for the following tests and procedures. They are part of regular cancer care: Every 2 months for the first 2 years, then every 6 months for the next 3 years
- History and physical examination, including neurologic examination - MRI scan of your brain - History of corticosteroid use - Spinal tap (if you previously had cancer cells in the spinal fluid) will be obtained every 2 months until you have 2 MRIs showing no sign of disease
- An examination by an eye doctor, to see if there are cancer cells in the eyes (if you previously had evidence of cancer cells in the eyes)
You will need these tests and procedures that are either being tested in this study or being done to see

You will receive treatment for about 6-7 months. You will be seen in follow-up visits beginning 4 weeks after the start of cytarabine. You will be seen every 2 months for the first 2 years and every 6 months for the next 3 years.  
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Clinical trial: NCT01399372
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or not to take part in the study. If you decide to take part in this study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution.  
We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study.  
A Data Safety Monitoring Board will be regularly meeting to monitor safety and other data related to phase I, I/II, and II NRG Oncology clinical trials. The Board members may receive confidential patient information, but they will not receive your name or other information that would allow them to identify you by name.  
In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.
Clinical trial: NCT01399372
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: How The Study Is Affecting Your Body:|What Side Effects Or Risks Can I Expect From Being In The Study? (8/25/15)|Possible Side Effects Of Rituximab (Table Version Date: June 16, 2014) Common, Some May Be Serious In 100 People Receiving Rituximab,|Occasional, Some May Be Serious|Occasional, Some May Be Serious|Rare, And Serious|Rare, And Serious|Possible Side Effects Of Methotrexate (Table Version Date: October 8, 2013) Common, Some May Be Serious|Occasional, Some May Be Serious|Occasional, Some May Be Serious|Possible Side Effects Of Vincristine (Table Version Date: May 28, 2013) Common, Some May Be Serious|Possible Side Effects Of Cytarabine (Table Version Date: July 27, 2015) Common, Some May Be Serious|Occasional, Some May Be Serious In 100 People Receiving Cytarabine, From 4 To 20 May Have:|Rare, And Serious|Rare, And Serious|Possible Side Effects Of Whole Brain Radiation|What Happens If I Am Injured Because I Took Part In This Study?|Risks (10/28/13)

Every 2 months for 3 years, starting at the end of the first two years
- Telephone call: a study assistant will call you and ask questions about your disease status and other treatments you have received since your last visit to the doctor, if any. We may collect medical records, if you have received additional treatments.

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, researchers don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the chemotherapy and/or radiation. In some cases, side effects can be serious, long lasting, or may never go away. There also is a risk of death. You should talk to your study doctor about any side effects that you have while taking part in the study.

more than 20 and up to 100 may have:
- Nausea
- Chills, fever
- Reaction during or following infusion of the drug
- Infection, especially when white blood cell count is low
•
- Numbness and tingling of the arms and legs
- Tiredness

In 100 people receiving Rituximab, from 4 to 20 may have:
- Anemia which may require blood transfusions
- Bruising, bleeding
- Abnormal heartbeat
- Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and tiredness
- Sores in eye
- A tear or a hole in the stomach that may require surgery
- Diarrhea, vomiting
- Pain - Swelling of the body
- Hepatitis which may cause yellow eyes and skin
- Dizziness, headache
- Kidney damage which may require dialysis
- Cough
- Scarring of the lungs
- Stuffy nose
- Blockage of internal organs which may cause shortness of breath, wheezing, vomiting
- Increased sweating
- Itching, rash, blisters on the skin
- Severe skin rash with blisters and peeling which can involve mouth and other parts of the body
- Low blood pressure which may cause feeling faint

In 100 people receiving Procarbazine, from 4 to 20 may have:
- Anemia which may cause tiredness, or may require blood transfusions
- Infection, especially when white blood cell count is low OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Procarbazine, from 4 to 20 may have:
- Bruising, bleeding - A new cancer resulting from treatment of earlier cancer
- Muscle weakness
- Confusion - Sores in mouth which may cause difficulty swallowing
- Diarrhea RARE, AND SERIOUS
In 100 people receiving Procarbazine, 3 or fewer may have:
- None NOTE: You will be required to avoid some foods, such as alcohol, some cheeses and banana that can cause high blood pressure or nausea and vomiting when eaten with procarbazine. You will be given written diet instructions.

In 100 people receiving Rituximab , 3 or fewer may have:
- Damage to the brain caused by a virus which may result in tiredness, weakness, changes in thinking, and disability. This is called progressive multifocal leukoencephalopathy (PML).  
- Heart stops beating Additional information In people who have ever been infected with hepatitis B virus, there is a risk that the virus can flare up during treatment with drugs that affect your immune system, such as rituximab. This could lead to liver failure or even death. The risk of hepatitis B virus flaring up may continue for several months after you stop taking rituximab. If you become jaundiced (yellowing of the skin and eyes) or develop viral hepatitis while taking rituximab or after stopping treatment, you should tell your study doctor immediately. Your study doctor will discuss this risk with you and explain what testing is recommended to check for hepatitis.  
Other symptoms may occur, usually within 30 to 120 minutes of beginning the first infusion, and include nausea, vomiting, itching, hives, swelling of the lips or throat, lowered blood pressure, increased blood pressure, headache, difficulty breathing, throat irritation, running nose, rash, decreased appetite, muscle aches, or dizziness. These symptoms generally improve with each treatment and respond to slowing or interrupting the therapy and treating the symptoms.

In 100 people receiving Cytarabine, 3 or fewer may have:
- Coma  
OCCASIONAL, SOME MAY BE SERIOUS  
  
  
  
  
RARE, AND SERIOUS  
  
  
In 100 people receiving Whole Brain Radiation, 3 or fewer may have:

In 100 people receiving Methotrexate, more than 20 and up to 100 may have:
- Increased risk of sunburn, rash OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Methotrexate, from 4 to 20 may have:
- Scarring of the lungs which may cause shortness of breath
- Fluid around heart
- Internal bleeding which may cause belly pain, black tarry stool, blood in vomit
- Nausea, vomiting, diarrhea
- Sores in mouth which may cause difficulty swallowing
- Liver damage which may cause yellowing of eyes and skin
- Scarring of the liver - Hepatitis
- Hair loss
- Bruising, bleeding
- Infection, especially when white blood cell count is low
- Anemia which may cause tiredness, or may require transfusion
- A new cancer resulting from treatment of earlier cancer
- Confusion
- Seizure - Kidney damage which may require dialysis
- Severe skin rash with blisters and peeling which can involve mouth and other parts of the body
- Blood clot which may cause swelling, pain, shortness of breath
•

In 100 people receiving Rituximab, from 4 to 20 may have:
- Anemia which may require blood transfusions
- Bruising, bleeding
- Abnormal heartbeat
- Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and tiredness
- Sores in eye
- A tear or a hole in the stomach that may require surgery
- Diarrhea, vomiting
- Pain - Swelling of the body
- Hepatitis which may cause yellow eyes and skin
- Dizziness, headache
- Kidney damage which may require dialysis
- Cough
- Scarring of the lungs
- Stuffy nose
- Blockage of internal organs which may cause shortness of breath, wheezing, vomiting
- Increased sweating
- Itching, rash, blisters on the skin
- Severe skin rash with blisters and peeling which can involve mouth and other parts of the body
- Low blood pressure which may cause feeling faint

In 100 people receiving Procarbazine, from 4 to 20 may have:
- Anemia which may cause tiredness, or may require blood transfusions
- Infection, especially when white blood cell count is low OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Procarbazine, from 4 to 20 may have:
- Bruising, bleeding - A new cancer resulting from treatment of earlier cancer
- Muscle weakness
- Confusion - Sores in mouth which may cause difficulty swallowing
- Diarrhea RARE, AND SERIOUS
In 100 people receiving Procarbazine, 3 or fewer may have:
- None NOTE: You will be required to avoid some foods, such as alcohol, some cheeses and banana that can cause high blood pressure or nausea and vomiting when eaten with procarbazine. You will be given written diet instructions.

In 100 people receiving Vincristine, more than 20 and up to 100 may have:
- Constipation
- Hair loss
- Pain or redness at the site of injection
- Numbness and tingling of fingers or toes
- Headache, jaw pain and/or muscle pain - Weakness and difficulty walking
- Swelling of lower legs OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Vincristine, from 4 to 20 may have:
- Anemia which may cause tiredness, or may require transfusion
- Drooping eyelids - Hoarseness RARE, AND SERIOUS
In 100 people receiving Vincristine, 3 or fewer may have:
- Seizure

In 100 people receiving Cytarabine, more than 20 and up to 100 may have:
- Blood clot
- Rash
- Swelling in the rectum which may cause rectal pain - Diarrhea, loss of appetite, nausea, vomiting - Sores in mouth which may cause difficulty swallowing
- Anemia which may cause tiredness, or may require blood transfusions
- Fever OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Cytarabine, from 4 to 20 may have:
- Infection, especially when white blood cell count is low

- Bruising, bleeding - Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
- Numbness and tingling of the arms and legs
- Severe blood infection - Kidney damage which may cause swelling, may require dialysis
- Headache
- Dizziness - Chest pain
- Hair loss
- Liver damage which may cause yellowing of skin or eyes - Swelling and redness of the eye

In 100 people receiving Rituximab , 3 or fewer may have:
- Damage to the brain caused by a virus which may result in tiredness, weakness, changes in thinking, and disability. This is called progressive multifocal leukoencephalopathy (PML).  
- Heart stops beating Additional information In people who have ever been infected with hepatitis B virus, there is a risk that the virus can flare up during treatment with drugs that affect your immune system, such as rituximab. This could lead to liver failure or even death. The risk of hepatitis B virus flaring up may continue for several months after you stop taking rituximab. If you become jaundiced (yellowing of the skin and eyes) or develop viral hepatitis while taking rituximab or after stopping treatment, you should tell your study doctor immediately. Your study doctor will discuss this risk with you and explain what testing is recommended to check for hepatitis.  
Other symptoms may occur, usually within 30 to 120 minutes of beginning the first infusion, and include nausea, vomiting, itching, hives, swelling of the lips or throat, lowered blood pressure, increased blood pressure, headache, difficulty breathing, throat irritation, running nose, rash, decreased appetite, muscle aches, or dizziness. These symptoms generally improve with each treatment and respond to slowing or interrupting the therapy and treating the symptoms.

In 100 people receiving Cytarabine, 3 or fewer may have:
- Coma  
OCCASIONAL, SOME MAY BE SERIOUS  
  
  
  
  
RARE, AND SERIOUS  
  
  
In 100 people receiving Whole Brain Radiation, 3 or fewer may have:

Common, Some May Be Serious In 100 People Receiving Whole Brain Radiation, More Than 20 May Have: - Scalp Redness Or Soreness - Hair Loss, Which May Be Temporary Or Permanent - Short Term Hearing Loss - Tiredness - Temporary Increase Of Brain Tumor Symptoms Such As Headaches, Seizures, Or Weakness  
- Getting treatment or care for your cancer without being in a study - Taking part in another study
- Getting no treatment
- Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.  
Talk to your study doctor about your choices before you decide if you will take part in this study.

It is important that you tell your study doctor, __________________ *[investigator's name(s)],* if you feel that you have been injured because of taking part in this study. You can tell the study doctor in person or call him/her at
__________________ *[telephone number].*
You will get medical treatment if you are injured as a result of taking part in this study. You and/or your health plan will be charged for this treatment. The study will not pay for medical treatment.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small. Some of your genetic and health information may be placed in central databases that may be public, along with information from many other people. Information that could directly identify you will not be included. The samples are given a code to protect your privacy before they are used. Any related information given to researchers will also be coded. Researchers will receive the code instead of any information that might directly identify you.  
There can be a risk in knowing genetic information. New health information about inherited traits that might affect you or your blood relatives could be found during a research study. Even though your genes are unique, you share some of the same genes with your blood relatives.  
Although we are not able to know all of the risks from taking part in research on inherited traits, we believe that the risks to you and your family are very low, because your samples will be coded. Research results will not be returned to you or your doctor.  
Very rarely health or genetic information could be misused by employers, insurance companies, and others. For example, life insurance companies may charge a higher rate based on this information.  
Many states have laws to protect against genetic discrimination [list appropriate state information if your state or locality has such laws]. Additionally, a federal law called the Genetic Information Non-Discrimination Act, or GINA,
is in effect. This law prohibits health insurer or employer discrimination. The law does not include other types of misuse by life insurance, disability, or long term care insurance. To learn more about the GINA Law, please ask
[Note to local investigator: Contact information for patient representatives or other individuals in a local institution who are not on the IRB or research team but take calls regarding clinical trial questions can be listed here.]
Clinical trial: NCT01399372
Section: Procedures
Subsections: What Will Happen If I Take Part In This Research Study?|During The Study … (1/31/13)|Study Plan

You will be "randomized" into one of the study groups described below. Randomization means that you are put into a group by chance. A computer program will place you in one of the study groups. Neither you nor your study doctor can choose the group you will be in. You will have an equal chance of being placed in any group.  
If you are in group 1 (often called "Arm A") …
You will receive chemotherapy with rituximab, methotrexate (MTX), procarbazine, and vincristine. You will receive the chemotherapy for four 28-day cycles (for approximately 4 months total) on several days each cycle as follows:
- Day 1: Rituximab (given by vein, as an outpatient). The first treatment will last approximately 5 hours, but subsequent treatments may be shorter, according to your physician.  
- Day 2: MTX and vincristine (vincristine is given during cycles 1 and 2 only). These will be given by vein in the hospital. MTX is given over 2 hours and vincristine is given over approximately one minute. You will need to stay in the hospital for approximately 3-5 days, until the MTX is eliminated from your body.  
- Days 2-8: Procarbazine (given by mouth, once a day, on an empty stomach). While you are on procarbazine:
- You should not to drink alcoholic beverages while you are taking procarbazine since it may cause nausea, vomiting, and serious flushing.  
- You will need to avoid foods with high tyramine content such as wine, yogurt, ripe cheese and bananas.  
- You will need to avoid over-the-counter drug preparations containing antihistamines or sympathomimetic drugs (drugs are used to treat low blood pressure and cardiac arrest, reduce nasal stuffiness, delay premature labor, and treat other things). Ask your physician or pharmacist before using any over-the-counter drug.  
- You will be asked to keep a diary where you will record the number of procarbazine pills you take each day. At your next clinic visit, you will be asked to bring the diary and the procarbazine bottle with the remainder of pills left.
- Day 15: Rituximab (given by vein, as an outpatient) - Day 16: MTX and vincristine (vincristine is given during cycles 1 and 2 only). These will be given by vein in the hospital, as described above.  
When you have finished receiving the four cycles of chemotherapy with rituximab, MTX, procarbazine, and vincristine, you will receive two 28-day cycles (approximately 2 months total) of additional chemotherapy on several days each cycle as follows:
- Days 1 and 2: Cytarabine (given by vein as an outpatient). Cytarabine is given over 3 hours.  
If you are in group 2 (often called "Arm B")…
You will receive chemotherapy with rituximab, methotrexate (MTX), procarbazine, and vincristine as described above. If your tumor has not grown during the chemotherapy, you will then receive the reduced-dose radiation therapy to your brain daily for a total of 13 days. If however your tumor has grown, your doctor will discuss other treatment alternatives with you. When you have finished the radiation therapy, you will receive chemotherapy with cytarabine as described above.

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will need the following tests and procedures. These exams, tests or procedures are part of regular cancer care 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. This will be up to your study doctor.  
Within 2 weeks before starting treatment
- Blood tests for bone marrow function, liver function, renal function, electrolyte levels, - Urine test - Chest X-ray - MRI scan of your brain - History and physical examination, including neurologic examination, assessment of ability to carry out activities of daily living, and history of corticosteroid use An examination by an eye doctor, to see if there are cancer cells in the eyes Within 6 weeks before starting treatment
- A spinal tap will be required, for examination of the cerebrospinal fluid (a fluid that bathes the brain and the spinal cord). This procedure is routinely done to see if there are cancer cells in cerebrospinal fluid. You will receive local anesthesia for that.  
- A bone marrow biopsy will be required, to look for cancer cells in the bone marrow.  
- A blood test for hepatitis B screening is recommended.  
Every week during treatment with rituximab, methotrexate, procarbazine and vincristine
- Blood tests for bone marrow function Every 2 weeks during treatment with rituximab, methotrexate, procarbazine and vincristine
- History and physical examination, including neurologic examination
- Blood test to determine the level of methotrexate in your blood (and then daily until the methotrexate is cleared)
- Blood tests for liver function, renal function, and electrolyte levels (and then daily until the methotrexate is cleared)
Every other month during treatment with rituximab, methotrexate, procarbazine and vincristine
- MRI scan of your brain - Assessment of ability to carry out activities of daily living - History of corticosteroid use Every week during cytarabine treatment
- Blood tests for bone marrow function Every month during cytarabine treatment
- History and physical examination, including neurologic examination - Assessment of ability to carry out activities of daily living
- Blood tests for liver function, renal function, and electrolyte levels Once during cytarabine treatment (for patients assigned to Arm B/whole brain radiation treatment)
- MRI scan of your brain - History of corticosteroid use

Another way to find out what will happen to you during the study is to read the chart below. Start reading at the top and read down the list, following the lines and arrows.
Clinical trial: NCT01399372
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

PCNSL is a disease that can be cured in less than half of patients with a combination of chemotherapy and standard brain radiation. Unfortunately, the combination of chemotherapy and standard brain radiation may cause serious damage to the brain. When this occurs, patients develop progressive memory and other neurologic problems that can be fatal. Because of this risk, many patients and physicians prefer to avoid radiotherapy. However, this results in higher risks of disease coming back. Many patients end up requiring radiotherapy anyway. As a new alternative, radiotherapy has been used in significantly lower doses. In a previous study, this seemed to achieve the same rates of cure as full doses of radiotherapy but with much less risk of neurologic side effects. The purpose of this study is to determine the effects, good and/or bad, of the combination of low-dose whole brain radiation plus chemotherapy on you and your tumor compared with chemotherapy alone, to find out which is better. In this study, you will either get the experimental treatment (chemotherapy plus reduced-dose whole brain radiation) or chemotherapy alone.
Clinical trial: NCT01399372
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?

Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping or decide to stop. He or she will tell you how to stop safely.  
It is important to tell the study doctor if you are thinking about stopping so any risks from the chemotherapy and/or radiation can be evaluated by him/her. Another reason to tell your study doctor that you are thinking about stopping is to discuss what follow-up care and testing could be most helpful for you.  
The study doctor may stop you from taking part in this study at any time if he/she believes it is in your best interest; if you do not follow the study rules; or if the study is stopped.