Clinical trial: NCT01951885
Section: Alternatives
Subsections: Alternative Procedures Of Treatment

If you do not wish to participate in this study, you will be treated with standard GVHD therapy according to the type of preparative regimen and type of donor being used for your allogeneic hematopoietic cell transplant.
Clinical trial: NCT01951885
Section: Confidentiality
Subsections: Privacy And Confidentiality Authorization To Use Or Disclose (Release) Health Information That Identifies You For A Research Study

If you volunteer to participate in this research, your protected health information (PHI) that identifies you will be used or disclosed to Dr. Betty Hamilton and the research staff at Cleveland Clinic for the purposes of this research and to Case Western Reserve University for administration. The PHI that we may use or disclose (release) for this research may include your name, address, phone number, date of birth, Social Security number, information from your medical record, lab tests, or certain information relating to your health or condition. Some of the tests and procedures done solely for this research study may also be placed in your medical record so other doctors know you are in this study. Upon completion of the study, you may have access to the research information that is contained in your medical record. In addition to the investigators and research staff listed above, your PHI may be looked at by other groups involved with the study such as the Cleveland Clinic Institutional Review Board, and the Case Comprehensive Cancer Center Protocol Review and Monitoring Committee. Your PHI may also be used by and/or disclosed (released) to:  
The Food and Drug Administration; The Department of Health and Human Services; The National Cancer Institute (NCI);
Other Institutional Review Boards; Data Safety and Monitoring Boards;
Once your personal health information is released it may be re-disclosed and no longer protected by privacy laws. Your research information may be used and disclosed indefinitely, but you may stop these uses and disclosures at any time by writing to Dr. Betty Hamilton, Cleveland Clinic R35, 9500 Euclid Avenue, Cleveland, OH 44195 or calling 216/445-7580. . Your participation in the research will stop, but any information previously recorded about you cannot be removed from the records and will continue to be used as part of this research. Also, information already disclosed outside the Cleveland Clinic cannot be retrieved. This will not affect your rights to treatment or benefits outside the research study. The Cleveland Clinic will not use your information collected in this study for another research purpose without your written permission; unless the Cleveland Clinic Institutional Review Board (IRB) assures your privacy and confidentiality is protected. The IRB is a committee whose job it is to protect the safety and welfare of research subjects. By signing this informed consent form, you are authorizing such access to your research and medical record information. If you choose not to sign this consent form, you will not be able to participate in this research study. This Authorization does not have an expiration date.
Clinical trial: NCT01951885
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks|Risk And Side Effects Of Tacrolimus|Risk And Side Effects Of Methotrexate|Reproductive Health/Sexual Activity|Research-Related Injury|Risks Of Stored Material And Genetic Testing

GVHD is caused by an immune attack on your tissues from the transplanted donor cells and there for all treatments for GVHD include drugs to suppress (turn off) this immune attack. All of the drugs in this study can increase your chance of infection including the standard treatment for GVHD. There for you will take several protective antibiotics and be watched carefully for an infections while you are being treated for GVHD. Tell your doctors immediately if you get a fever, chills, a cough or any other symptoms that might be part of an infection. All of the drugs in this study can have risk and side effects, including the standard treatment for GVHD. Your doctors will watch you carefully for any side effects and will modify your treatment if they develop. The drugs used in this study may cause all, some or none of the side effects listed below. In addition, there is always the risk that you might experience side effects or other adverse reactions which other patients before you have not experienced Side effects that we know about are described in the tables below. Side effects are categorized into either:
Likely - This type of side effect is expected to occur in more than 20% of patients.  
This means that 21 or more patients out of 100 might get this side effect  
Unlikely - This type of side effect is expected to occur in 20% of patients or fewer.  
This means that 20 patients or fewer out of 100 might get this side effect Rare, but Serious - This type of side effect does not occur very often, in fewer than 2% of patients, but is serious when it occurs. This means that 1 or 2 patients (or fewer) out of 100 might get this side effect.  
| Likely                                                                                                                                                                                                                                                                                                            | Less Likely                                                                                                                                                                                                                                                                                                                                                                                                              | Rare but Serious   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
|  Reversible, but  sometimes irreversible  damage to the kidneys  Loss of magnesium,  calcium and potassium  High blood pressure  Tremors (shaking of  the hands)  Increases in blood  lipids/fats (cholesterol  and triglycerides)                                                                           |  Seizures  Changes in vision  Dizziness  Red blood cell destruction  Progressive multifocal  leukoencephalopathy, a rare  disease caused by a virus  which causes progressive  damage to the white matter of  the brain.   Posterior reversible  encephalopathy syndrome  (PRES), a rare neurologic  syndrome typically including  symptoms of elevated blood  pressure, headache, confusion  and possibly seizure |                    |
| It is very important that you do not eat grapefruit or drink grapefruit juice while taking  Tacrolimus. It is very important that you do not drink soft drinks containing bergamottin.   Nausea  Vomiting  Liver problems  Changes to the brain  that may cause  confusion  Insomnia  Unwanted hair  growth |                                                                                                                                                                                                                                                                                                                                                                                                                          |                    |

| Likely                                                                                                                                                                                                                    | Less Likely                                  | Rare but Serious                                                                                                                                                                                                                                                         |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|  Miscarriage  Birth defects  Diarrhea  Damage to unborn baby  Limited effectiveness of  birth control  Stomach pain  Upset stomach  Vomiting   Headache  Tremors (shaking of the  hands)  Low white blood cell |                                             | Low red blood cell count  (anemia)                                                                                                                                                                                                                                       |
|                                                                                                                                                                                                                          | Rash                                         |                                                                                                                                                                                                                                                                          |
|                                                                                                                                                                                                                          | Difficulty falling asleep or  staying asleep |                                                                                                                                                                                                                                                                          |
|                                                                                                                                                                                                                          | Dizziness                                    |                                                                                                                                                                                                                                                                          |
|                                                                                                                                                                                                                          | Uncontrollable hand  shakes                  |  Difficulty breathing  Unusual bruising  Fast heartbeat  Excessive tiredness  Weakness  Blood in stool  Bloody vomit  Change in vision  Progressive multifocal  leukoencephalopathy, a  rare disease caused by a  virus which causes  progressive damage to the |

| white matter of the brain.   |
|------------------------------|  
| bruise and bleed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                                                       |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------|
|  Learning disability  Dizziness  Sense of not feeling well  or tiredness  Drowsiness  Blurred vision  Rashes with itching and  hives  Hair loss, inflammation of  the hair follicles  Acne  Tearing and inflammation  of the eyes  Darkening of the  fingernails                                                                                                                                                                                                                                                                                                                                                                                       | tissue which may make  you short of breath and  cough |
|  Seizures  Temporary damage to the  brain such that you may  experience headaches,  drowsiness, difficulty  speaking or forming  words, blurred vision or  temporary blindness, and  decreased reflexes  Temporary loss of  function or feeling in the  lower part of the body  (partial paralysis)  Severe damage to brain  tissue which over time  could lead to difficulty  carrying out normal daily  tasks or could lead to a  coma.  Inflammation and scarring  of the liver  Damage to the bone  which could lead to  arthritis pain and  weakness of the bone  Inflammation of the heart  Fluid buildup around the  heart  Damage to the kidney |                                                       |

Because the risk to an unborn child (human embryo, fetus) or pregnant/lactating woman is unknown, you can NOT participate in this study if you are a female of childbearing potential unless you have a current negative pregnancy test. In addition, whether you are male or female, you must agree to either complete abstinence from heterosexual intercourse or use (two) medically approved forms of birth control for the duration of the study. You will agree to inform your doctor immediately if:
1) you have any reason to think you may be pregnant 2) you find that there is now a risk of you becoming pregnant 3) you have stopped using a medically approved form of birth control Acceptable methods of birth control include: birth control pills, birth control implants (depo-provera), diaphragm, intrauterine device (IUD), cervical cap and condoms with spermicide.

If injury occurs as a result of your involvement in this research, medical treatment is available from Cleveland Clinic or another medical facility but you/your medical insurance will be responsible for the cost of this treatment. A research injury is an injury that happens as a result of taking part in this research study. If you are injured by a medical treatment or procedure that you would have received even if you weren't in the study, that is not considered a "research injury". There are no plans for payment of medical expenses or other payments, including lost wages, for any research-related injury. To help avoid injury, it is very important to follow all study directions. Further information about research-related injuries is available by contacting the Cleveland Clinic Institutional Review Board at (216) 444-2924

There may be unknown risks associated with the storage of samples. The samples contain genetic information (i.e. DNA) therefore can potentially be used to determine paternity or for the release of private health information. However, there are no plans to test for specific genetic diseases with your samples. We will make every attempt to insure that your personal information will be confidential, but complete confidentiality cannot be guaranteed. A new federal law, called the Genetic Information Nondiscrimination Act (GINA), effective May 21, 2010, generally makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on genetic information. This law generally will protect you in the following ways: (1) Health insurance companies and group health plans may not request your genetic information that we get from this research and may not use your genetic information when making decisions regarding your eligibility or premiums; and (2) Employers with 15 or more employees may not use your genetic information from this research when making a decision to hire, promote, or fire you or when setting terms of your employment. This new federal law does not apply to companies that sell life insurance, disability insurance, or long-term care insurance and does not protect you against discrimination based on an already diagnosed genetic condition or disease.
Clinical trial: NCT01951885
Section: Procedures
Subsections: Study Procedures|Randomization/Study Intervention|Study Assessments

Your participation in this study will last for one year after your hematopoietic cell transplant. You will take the GVHD drugs in Group A or B for at least 100 days and then your doctor will begin to taper the medications if you do not show any signs of GVHD. The taper is usually done by approximately 180 days, but may be longer if there are signs or symptoms of GVHD.  
Your doctor may decide to stop or adjust the dose of the GVHD drugs you are receiving before 100 days for many reasons including if:
It is considered to be in your best interest Pregnancy occurs during the course of therapy The study is temporarily or prematurely suspended You experience excessive toxicity to one of the drugs
If you are removed from the research study, your doctor will explain to you why you were removed. Your doctor will decide with you, what further treatment is needed or available for GVHD treatment. In addition, you can choose to stop participating in the research study at any time. However, if you decide to end your participation in this study, we encourage you to talk to your doctor first. It is standard of care to be followed closely after your hematopoietic cell transplant. These details are discussed in the treatment consent for your transplant. All of the assessments, tests, hospital stays and follow up appointments for this study are part of the standard of care for your hematopoietic cell transplant.  
Screening The evaluations to determine if you are eligible for this study will take place during your staging appointments for your hematopoietic cell transplant. All of these test and assessments are done as part of your transplant evaluation. These include the following:
Age, gender, race Medical history Complete physical exam Disease assessment of tumor or site involved Weight Performance status (ECOG or Lansky scores). These scores represent how a person's disease affects the daily living activities and abilities of the person.  
Laboratory test results including complete blood count and differential, liver enzyme tests, coagulation tests, and tests to see if you have been exposed to viruses such as cytomegalovirus (CMV) and the AIDS virus.  
Pregnancy test for female of childbearing age Pulmonary function testing

If these evaluations show that you are eligible to participate in this research study and you choose to participate in this study, you will be assigned to Group A or Group B by chance using a process similar to the flip of a coin. This process is called randomization. Neither you nor the study staff will select the group to which you will be assigned. You will receive Tacrolimus starting the day before (day -1) you receive your donor cells (day 0) regardless of which group you are assigned to. Tacrolimus is given once a day and will continue for 100 days after your transplant. Tacrolimus will be given intravenously but will be changed to oral medication when you can tolerate it. If you are in Group B, you will also receive Mycophenolate starting the day after (day +1) your transplant and continuing for 45. Mycophenolate is given two times a day. Mycophenolate will be given intravenously but will be changed to oral medication when you can tolerate it.  
Both Tacrolimus and Mycophenolate can be tapered after day 100 and day 45 respectively if there is not any evidence of GVHD. This will be decided by your doctor.  
If you are in Group A, you will receive one Methotrexate dose of 15 mg/m2on the day after your transplant (day +1) and one Methotrexate dose of 10 mg/m2on day +3, day +6, and day +
11. Methotrexate is given intravenously. This is considered the standard dose of Methotrexate.  
If you are in Group B, you will receive a "mini-dose" of Methotrexate on day +1, day +3 and day +6. This "mini-dose" will be 5 mg/m2of Methotrexate.

After your hematopoietic cell transplant, data will be collected. All of the test and assessments are standard of care for patients undergoing a hematopoietic cell transplant. The following is a list of parameters that will be followed in this study after your transplant:
Performance status (ECOG or Lansky). These scores represent how a person's disease affects the daily living activities and abilities of the person.  
Disease/tumor assessments Weight Laboratory test including complete blood count and differential, liver enzymes and coagulation studies Laboratory tests to monitor for infection with the Cytomegaolvirus (CMV), a common virus which can cause infection when you are immunosuppressed.  
Degree of inflammation and sores (mucositis) in your oral cavity from chemotherapy and medications.  
GVHD monitoring Laboratory tests to determine the percent of donor white cells compared to your own white cells in your blood (chimerism studies) to monitor how well your donor cells are growing in your bone marrow.  
Tacrolimus serum levels Organ (liver, kidney and pulmonary) toxicity assessments Infection Need for parenteral nutrition, which is nutrition given intravenously through a catheter if you are unable to eat.  
Use of intravenous medicine to control your pain.  
The above parameters will be followed for one year after your transplant.
Clinical trial: NCT01951885
Section: Purpose of Research
Subsections: Purpose

You are being asked to participate in this research study because you have a medical disease called a hematological or lymphoproliferative malignancy (cancer of the blood) and have agreed to undergo an allogeneic hematopoietic cell transplant. This means the stem cells you receive for your transplant will come from a donor. The details of the transplant procedure are explained in a separate consent form. When you have an allogeneic transplant, you may get another disease called graft-versus-host disease (GVHD). GVHD is a reaction that occurs when donor bone marrow or peripheral blood stem cells are infused into your body and sees your body as foreign. As a result, this damages many tissues and affects your immune system. Many organs of the body (skin, (including hair), eyes, mouth, liver, joints, muscles and bowel) can be damaged by this immune disorder. GVHD can cause skin rashes, feeling sick to your stomach, throwing up, abdominal pain, diarrhea and/or yellowing of the skin or eyes. In severe cases, it can cause death. You will be given drugs that have been shown to help prevent you from getting GVHD or to lessen the severity of it. You will start GVHD prevention around the time you get your donor cells and it can last many months after the transplant. The purpose of this study is to compare the effectiveness two different combinations of GVHD medications to prevent or lessen the severity of GVHD. One is using a standard of treatment regimen consisting of Methotrexate and Tacrolimus. The other treatment plan uses a lower dose of Methotrexate with Tacrolimus and Mycophenolate. All of the drugs being used in this study are approved by the U.S. Food and Drug Administration (FDA) for helping to prevent (or lessen the severity of) graft versus host disease. This study consists of two study groups. Group A will receive the standard dose of Methotrexate with Tacrolimus. Group B will receive a "mini-dose" of Methotrexate with Tacrolimus and Mycophenolate. If you decide to join the study, you will be randomly assigned to Group A or B. If you choose not to join the study, you will receive standard treatment for GVHD.  
About 100 people will take part in this research study at Cleveland Clinic
Clinical trial: NCT01951885
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this research study is voluntary. Choosing not to participate will not alter your usual health care or involve any penalty or loss of benefits to which you are otherwise entitled. If you decide to join the study, you may withdraw at any time and for any reason without penalty or loss of benefits. If information generated from this study is published or presented, your identity will not be revealed. In the event new information becomes available that may affect the risks or benefits associated with this study or your willingness to participate in it, you will be notified so that you can decide whether or not to continue participating.  
Termination of Participation Your participation in this study may be discontinued by your doctor or the investigator in charge of the study without your consent for any reason, including but not limited to:
His/her judgment that any condition or circumstance may jeopardize your welfare or the integrity of the study Your failure to follow instructions of your doctor or the investigator If the study is stopped by the investigator and/or your doctor before completion of the study.