Clinical trial: NCT01596699
Section: Alternatives
Subsections: Are There Benefits To Taking Part In The Study?|What Other Choices Do I Have If I Do Not Take Part In This Study?

Taking part in this study may or may not make your child's health better. While doctors hope the addition of clofarabine to standard busulfan and fludarabine prior to transplant will be more useful compared to the usual treatment, there is no proof of this. We do know that the information from this study will help doctors learn more about the addition of clofarabine to standard busulfan and fludarabine prior to transplant. This information could help future transplant patients.

Your child's other choices may include:
Getting treatment or care for your child's cancer or non-malignant condition without being in a study. The standard transplant conditioning regimen for a patient like you consists of only busulfan, fludarabine, and alemtuzumab or rabbit ATG, without the addition of clofarabine. This is available off-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 or non-malignant condition. It does not treat the cancer or non-malignant condition directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Please talk to your child's doctor about your child's choices before deciding if he/she will take part in this study.
Clinical trial: NCT01596699
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?

We will do our best to make sure that the personal information in your child's medical record is kept private. However, we cannot guarantee total privacy. Your child's personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your child's name and other personal information will not be used.  
Organizations that may look at and/or copy your child's medical records for research, quality assurance, and data analysis include:
The National Cancer Institute (NCI) and other government agencies, e.g., the Food and Drug Administration (FDA), involved in keeping research safe for people.  
The University of California
Participation in research may involve a loss of privacy, but information about your child will be handled as confidentially as possible. A medical record will be created because of your child's participation in this study. Your child's consent form and some of your child's research test results will be included in this record. Therefore, your child's other doctors may become aware  
  
of your child's participation. Hospital regulations require that all health care providers treat information in medical records confidentially.
Clinical trial: NCT01596699
Section: Duration of Study Involvement
Subsections: When You Are Finished Receiving Clofarabine...|How Long Will I Be In The Study?

After discharge from the hospital, your child will be asked to return to the clinic on the following schedule:
every 1-4 weeks for the first six months then, every 3 months until 2 years post-transplant, then, every 6 months until 3 years post-transplant yearly thereafter until 5 years post-transplant At these visits, blood (2-4 teaspoons) will be taken to monitor your child's immune system in addition to assessing the function of the kidneys and liver. These tests are considered a part of your child's standard medical care. If your child no longer has a central venous line, the blood sample will be drawn by inserting a needle into a vein in your child's arm.  
Study location: All study procedures will be done at the UCSF Benioff Children's Hospital inpatient bone marrow transplant unit.

Your child will stay in the hospital for approximately 6-8 weeks to monitor him/her for sideeffects of your child's transplant and the treatment with clofarabine. However, we would like to continue to monitor your child's health for at least 5 years after your child's transplant. Keeping in touch with you and checking on your child's condition every year helps us look at the longterm effects of the study. We will ask your child to return to the clinic every 1-4 weeks for the first six months, then every 3 months until 2 years post-transplant, every 6 months until 3 years post-transplant, and yearly thereafter until 5 years post-transplant.
Clinical trial: NCT01596699
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?

Taking part in this study is your child's choice. Your child may choose either to take part or not to take part in the study. If your child decides to take part in this study, your child may leave the study at any time. No matter what decision your child makes, there will be no penalty to him/her and your child will not lose any of his/her regular benefits. Leaving the study will not affect your child's medical care. Your child can still get his/her medical care from our institution. We will tell you and your child about new information or changes in the study that may affect your child's health or your child's willingness to continue in the study. In the case of injury resulting from this study, your child does not lose any of his/her legal rights to seek payment by signing this form.
Clinical trial: NCT01596699
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Side Effects Or Risks Can I Expect From Being In The Study?|Risks And Side Effects Related To The Study Drug Clofarabine:|Likely **Nausea And/Or Vomiting**|Less Likely **Inflammation And/Or Sores In The Mouth That May Make Swallowing Difficult And Are** Painful (Painful Mouth Sores)|Rare But Serious **Inflammation Or Damage To The Liver Which Can Be Severe And Life-Threatening And** Which May Lead To An Enlarged Liver And Spleen, Bleeding From The Veins In The|Other Risks|What Happens If I Am Injured Because I Took Part In This Study?|Treatment And Compensation For Injury:|Risks

Your child may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your child's health care team may give your child medicines to help lessen side effects. Many side effects go away soon after your child stops taking the clofarabine. 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 child's study doctor about any side effects your child experiences while taking part in the study. Clofarabine is approved at a specific dose for use in treating children with a specific form of leukemia. Many risks and side-effects have been reported with that dose of clofarabine. However, you will receive a dose of clofarabine that is only 15% of the approved dose. However, you will receive clofarabine in combination with two other chemotherapy drugs, busulfan and fludarabine, and this combination may alter the types or severity of side-effects you experience. In adults undergoing transplant, busulfan has been combined with clofarabine doses.

Known risks and side effects related to standard-doses of clofarabine are listed below. Sideeffects that have been reported in four trials of clofarabine use in combination with other chemotherapy drugs prior to a transplant are listed first and are **bolded**.

**Diarrhea**
**Elevation in the blood of certain enzymes found in the liver and bilirubin (a substance**
that comes from the liver breaking down waste products) which may mean the liver is not working as well as normal
**Fever**
**Skin rash**
A fast heartbeat which may cause pain in the chest A feeling of extreme tiredness not relieved by sleep A decrease in blood pressure  
  
Pain in the abdomen (belly)
Fever with a low white blood cell count which could mean that you have an infection and might require hospitalization and treatment with antibiotics Chills Anxiety Loss of appetite Headache Skin rash with inflammation Itching Red spots on the skin from low platelets Bloody nose Fewer white blood cells, red blood cells and platelets in the blood (may be prolonged). A
low number of white blood cells can make it easier to get infections. A low number of red blood cells can make you feel tired and weak. A low number of platelets causes you to bruise and bleed more easily Abnormal levels of potassium or magnesium in the body which may require that you take extra potassium by mouth or vein An increase in an enzyme (called lipase) that helps break down fats in the body

**Increased levels of a chemical (creatinine) in the blood which could mean kidney**
damage
**The skin and the whites of the eyes appears yellow as a result of too much bilirubin (a**
substance that comes from the liver breaking down waste products) in the blood Severe rash with redness and pain on the palms of the hand and soles of the feet
(Hand-Foot Syndrome)
**Numbness and tingling in the fingers and toes**
**Rash with redness or red bumpy rash**
The rapid death of large numbers of tumor cells which can cause the potassium and phosphate salts and the uric acid in the blood to rise quickly and this could lead to a lifethreatening irregular heart beat or damage to the kidneys Fluid build-up in the tissues Sleepiness and weakness Changes to your child's emotions such that you feel depressed, anxious, agitated, irritable or confused Shaking chills High blood pressure Cough or shortness of breath Reddening of the face with feelings of warmth when the drug is infusing A fast rate of respiration that may cause pain in the chest Allergic reaction A change in alertness, concentration, and memory  
  
Constipation A life-threatening form of severe blood infection that usually results from the presence of bacteria and their toxins in the bloodstream and is characterized especially by persistent hypotension (low blood pressure) with reduced blood flow to organs and tissues and often organ dysfunction Tremor (shakiness usually of the hands)
Difficulty sleeping or falling asleep Fainting Low levels of oxygen in the blood which may make you feel short of breath Pain including back, bone, arm, or leg pain Weight loss Aches and pains in the muscles and joints Bleeding from the bladder, gut, mouth, or gums Vomiting or coughing blood Fluid build-up in the lungs that can make you feel short of breath A life threatening condition in which the level of oxygen in the blood becomes too low or the level of carbon dioxide in the blood becomes too high Damage to the sac around the heart which can lead to a build-up of fluid around the heart which may be painful and affect the ability of the heart to work normally but in most cases is only mild and temporary Bruising of the skin from low platelets Occasional sudden sharp pain in the rectal area Infections including those caused by bacteria, virus, and fungus and can be found in the lung, the blood, the skin and other places in the body Dizziness Abnormal high level of potassium in the blood which may cause irregular heart beat and require drug treatment to lower the level An increase in an enzyme (called amylase) that helps break down starch and sugars in the body A problem in nerve function that may cause pain, numbness, tingling, and muscle weakness in various parts of the body and may affect the ability to perform tasks that require fine movements

esophagus (the passage that leads from the throat to the stomach), a yellow appearance to the skin and fluid collection in the abdomen which makes it look larger Severe loss of water from the body (dehydration) which if untreated may cause low blood pressure and severe loss of salts such as sodium and potassium from the body and could lead to the kidneys failing which could be life-threatening Capillary leak syndrome: a condition in which fluid and proteins leak out of tiny blood vessels and flow into surrounding tissues, resulting in dangerously low blood pressure. Capillary leak syndrome may lead to multiple organ failure such as kidney, heart or liver failure and shock  
For more information about risks and side effects, ask your child's study doctor.  
  
IRB NUMBER: 12-08641 Inflammation of the pancreas (an organ in the abdomen which produces insulin and certain digestive chemicals) which may affect the function of the pancreas and which may cause pain in the abdomen (belly) which can be severe and may increase the blood sugar Severe inflammation and damage to the large intestine wall which can be life threatening Abnormal clotting of the blood that can lead to formation of blood clots and/or bleeding with abnormal findings on neurologic exam Severe rashes which can result in loss of skin and damage to mucous membranes and which may be life-threatening (occurred in combination of other drugs known to cause this effect)
Severe kidney damage (which may be permanent)
Failure of the bone marrow to produce blood cells and platelets which can be life threatening A change to the heart such that it does not pump the blood as well which may make you tired, weak, feel short of breath, and retain fluid

Study Drug Combination risks: The complete side effects of the combination of clofarabine, busulfan, and fludarabine are not yet known. It is possible that this combination of drugs will cause new or more serious side effects than taking these drugs separately. Your child will be monitored closely for side effects and your child's doctor may change your child's medications if it appears that this combination is causing serious side effects. You should tell your child's doctor about any side effects your child experiences while on this study. When additional information about side effects is known, your child will be notified of any further study drug related effects.  
Blood drawing (venipuncture) risks: Drawing blood may cause temporary discomfort from the needle stick, bruising, and infection. However, all of the study labs will be done while you are an inpatient and thus are planned to be drawn from your child's central venous line. Once your child is far out from transplant, labs required for routine transplant follow-up care may be drawn directly from your child's veins.  
Reproductive risks: Your child 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 to understand that your child needs to use birth control while on this study. Check with your child's 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. Some of the drugs used in the study may make your child unable to have children in the future.  
Unknown Risks: The experimental treatments may have side effects that no one knows about yet. The researchers will let your child know if they learn anything that might make you change your child's mind about participating in the study.

It is important that you tell your child's study doctor, Christopher Dvorak, if you feel your child has been injured because of taking part in this study. You or your child can tell the doctor in person or call him/her

If your child is injured as a result of being in this study, the University of California will provide necessary medical treatment. The costs of the treatment may be billed to you or your insurer just like any other medical costs, or covered by the University of California, depending on a number of factors. The University and the study sponsor do not normally provide any other form of  
  
compensation for injury. For further information about this, you may call the office of the Committee on Human Research at 415- 476-1814.

The greatest risk to your child is the risk of loss of privacy. Your child's blood samples will not be identified using your child's personal information. Your child's personal information will not be shared with the researchers. However, the researchers may have access to information about your child's health. There is a very small chance that your child's personal information may be released. We will do our best to make sure that your child's personal information is kept private.
Clinical trial: NCT01596699
Section: Procedures
Subsections: What Will Happen If I Take Part In This Research Study? Before You Begin The Main Part Of The Study...|During The Main Part Of The Study...|Day 0 - **Hematopoietic Stem Cell Transplant** Infusion Of Donor Hematopoietic Stem Cells

Your child will need to have the following exams, tests or procedures to find out if he/she can be in the main part of the study. These exams, tests or procedures are part of regular care prior to a transplant and may be done even if your child does not join the study. Your child will also have some procedures that are only being done because he/she is in the study. These are called study procedures and are noted as "study test" in the list of procedures below. If your child has had some of them recently, they may not need to be repeated. This will be up to your child's study doctor. Your child's screening visit may take up to 2 hours.  
Assessment of disease status, including bone marrow aspirate - Bone marrow aspirate collection will only be done for patients with cancer. A sample of your child's bone marrow aspirate may be collected to assess your child's bone marrow and to measure how much cancer is in your child's bone marrow. This test is done by inserting a needle into your child's hip bone to remove a sample of bone marrow aspirate (about 2 teaspoons). Your child will receive a medicine to numb the surface of the skin on your child's hip. This will take about 15-30 minutes. The bone marrow aspirate is considered a part of your child's standard medical care.  
Echocardiogram - This examination uses sound waves to make pictures of your child's heart, which helps determine how well your child's heart squeezes blood. Your child will be asked to lie on his/her left side while a technician places a probe with gel on your child's chest to create images of your child's heart to determine the function and size. The procedure is done in the cardiology department and will take approximately 45-60 minutes. The echocardiogram is considered a part of your child's standard medical care.  
Pulmonary function tests - Your child will have a breathing test performed where he/she breathes in and out of a machine to measure your child's breathing capacity. This will include a measurement of your child's blood oxygen which involves obtaining a sample of blood from the pulse area in your child's wrist. This is done in the Pulmonary department and takes about 20 minutes to complete. The pulmonary function test is considered a part of your child's standard medical care.  
Your child will have blood drawn:
o For routine blood tests o To measure your child's kidney function o For a pregnancy testing (as appropriate)

If the exams, tests and procedures show that your child can be in the main part of the study, and he/she chooses to take part, then your child will need the following tests and procedures. Placement of a central venous line - To make your child's chemotherapy treatment easier, a small thin tube (called a central venous catheter) will be placed under the skin below your child's collarbone (near your child's shoulder) that will connect to a large vein. This will allow for easy infusion of the chemotherapy drugs into your child's vein. This procedure is routinely performed by a surgeon in the outpatient setting. Your child will sign a separate consent form for this procedure. During your child's treatment, he/she will be in the hospital for at least 6-8 weeks. Following admission to the Blood and Marrow Transplant Unit at UCSF, your child will have the following procedures.  
Day -13 / Day -1 (1 to 13 days before hematopoietic stem cell transplant)
Administration of alemtuzumab for 3 days on Days -13 to -10 - only for patients with nonmalignant / stem cell defects. Your child's doctor will let you know if you need to have this treatment.  
Administration of busulfan for 5 days on Days -10 to -6. Administration of fludarabine for 4 days on Days -5 to -2. Administration of hydrocortisone for 4 days on Days -5 to -2 prior to clofarabine infusion to decrease the chance of an allergic reaction, such as itching or rash. Administration of clofarabine for 4 days on Days -5 to -2.  
Administration of rabbit anti-thymocyte globulin (rATG) for 4 days on Days -4 to -1. - for patients with malignancies getting unrelated donors or for patients receiving peripheral blood stem cells from a matched related donor. Your child's doctor will let you and your child know if your child needs to have this treatment.  
Blood draws (the blood will be drawn from your child's existing catheter)
o At time of admission *only* - For a study to see how your child's DNA (your child's genes) may affect the level of study medications in your child's body. This study is discussed in the *About Using Blood Samples for Research* section of this consent form. *Optional.*
o Daily - for routine blood tests, including monitoring of your blood salt levels o Daily from Day -5 to Day +6 (six days post stem cell transplant ) to monitor your child's liver - study test o For 4 days on Days -5 to -2 - to see how much of the medications are in your child's blood - study test.  
On Day -5, blood will be collected at 2, 4, 8, and 24 hours after you receive fludarabine.  
On Day -4 to -2, blood will be collected at 2 and 24 hours after administration of fludarabine for a total of 4 blood samples

Day 1 (after hematopoietic stem cell transplant) until discharge from the hospital A minimum of twice weekly monitoring of blood tests . Blood will be drawn from your child's existing catheter)
o For routine blood tests o To monitor your child's blood salt levels o To monitor your child's liver (this test will be done daily until Day 6 - six days post stem cell transplant) - study test Blood studies of donor cell engraftment beginning on approximately Day +30 and then monthly until stable.
Clinical trial: NCT01596699
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Benefits

The purpose of this study is to find out what effects, good and/or bad, the addition of clofarabine, a new chemotherapy agent, to a standard busulfan and fludarabine conditioning treatment has on your child's disease. The study will also look at what causes some people to have high drug levels of these medications in their body compared to other people that may have low drug levels even if they all receive the same dose of medication. Clofarabine is a new FDA approved chemotherapy drug that may provide extra killing of your child's cancer cells or lymphocytes, but may also be more toxic than standard treatments. Your child will be given both fludarabine and clofarabine as part of your child's chemotherapy. Busulfan is an FDA approved chemotherapy drug frequently used to prepare children for bone marrow transplantation. Busulfan is used to make space in the marrow to allow donor cells to grow, or engraft. Fludarabine is an FDA approved drug that effectively prevents rejection of the donor cells. The combination of clofarabine, busulfan and fludarabine is considered experimental which means it has not been approved by the US Food and Drug Administration.  
IRB NUMBER: 12-08641 NCT\# 01596699  
  
Funding for this study is being provided by the University of California, San Francisco Division of Pediatric Blood and Marrow Transplant.

Identifying and understanding specific factors that can influence drug levels in the body is important in order to help doctors better dose these drugs and prevent unwanted side-effects. The research that will be done with your child's blood may not help him/her. It might help people who have cancer and other diseases in the future. The benefits of research using blood include learning more about how your child's DNA may affect whether the study drug affects the disease.
Clinical trial: NCT01596699
Section: Voluntary Participation
Subsections: Making Your Child'S Choice|Consent

Please read each sentence below and think about your child's choice. After reading each sentence, put your initials in the "Yes" or "No" box. If you have any questions, please talk to your child's doctor or nurse, or call the UCSF Committee on Human Research at (415) 4761814. No matter what you decide to do, it will not affect your child's care.  
My child's blood may be collected to study his/her DNA.

You have been given copies of this consent form and the Experimental Subject's Bill of Rights to keep. You will be asked to sign a separate form authorizing access, use, creation, or disclosure of health information about you. PARTICIPATION IN RESEARCH IS VOLUNTARY. Your child has the right to decline to participate or to withdraw at any point in this study without penalty or loss of benefits to which he/she is otherwise entitled. Your child agrees to participate as a subject in the following research study objective: If your child wishes to be in this study, please sign below. PATIENT NAME: _____________________________________________________ (Print Name)  
Date Participant's Signature for Consent Date Person Obtaining Consent  
Date Signature of Witness (Required if participant is a non-English speaker) The person being considered for this study is unable to consent for himself/herself because s/he is a minor. By signing below, you are giving your permission for your child to be included in this study.  
Print name of subject  
Date Parent or Legal Guardian  
 Date Parent or Legal Guardian  
 Date Person Obtaining Consent  
| Date   | Signature of Witness (Required if participant is a non-English speaker)   |
|--------|---------------------------------------------------------------------------|
Clinical trial: NCT01596699
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?

Yes. Your child can decide to stop at any time. Tell the study doctor if your child is thinking about stopping or decide to stop. Your child may also tell your child's nurse and he/she will notify the study doctor that your child no longer wants to participate in the study. Your child's doctor will tell you how to stop your child's participation safely.  
  
It is important to tell the study doctor if your child is thinking about stopping so any risks from the clofarabine can be evaluated by your child's doctor. Another reason to tell your child's doctor that your child is thinking about stopping is to discuss what follow-up care and testing could be most helpful for your child. The study doctor may stop your child from taking part in this study at any time if he/she believes it is in your child's best interest, if your child does not follow the study rules, or if the study is stopped.