Clinical trial: NCT01991457
Section: Alternatives
Subsections: Aternatives

If you decide not to participate in the study, you may still be able to undergo allogeneic stem cell transplantation, but not as part of this study.  
If you decide not to undergo allogeneic stem cell transplantation, you may choose to continue chemotherapy or other non-transplant treatment. Or you may choose to receive palliative care (to relieve suffering and improve you quality of life, but not to cure your disease).  
Your doctor will discuss these choices and what other options may be available. Page 8 of 12
Clinical trial: NCT01991457
Section: Confidentiality
Subsections: Confidentiality|University Of Alabama At Birmingham Authorization For Use/Disclosure Of Health Information For Research

Any information gathered during this procedure will be kept confidential to the extent permitted by law. However, research information that identifies you may be shared with the UAB Institutional Review Board (IRB) and others who are responsible for ensuring compliance with law and regulations related to research, including people on behalf of UAB Bone Marrow Transplantation and Cellular Therapy Program; the U.S. Food and Drug Administration (FDA); and the Office for Human Research Protections (OHRP). The information from the research may be published for scientific purposes; however, your identity will not be given out.  
If any part of this study takes place at the University of Alabama Hospital this consent document will be placed in your file at that facility. The document will become part of your medical record chart. Your medical record will indicate that you are on a clinical trial and will provide the name and contact information for the principal investigator. Information relating to this study, including your name, medical record number, date of birth and social security nmber, may be shared with the billing offices of UAB and UAB Health System affiliated entities and its billing agents so that the costs for clinical services can be appropriately paid for by either the study account or by the patient/patient's insurance.  
Study records that have your name will be kept private. You will not be identified by nme in any publications related to this study. Your records will be given a unique code nmber. The key to the code will be kept in a locked file in the Research and Data Management offices of the BMTCT program.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by the U.S. Law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.

What is the purpose of this form? You are being asked to sign this form so that UAB may use and release your health information for research. Participation in research is voluntary. If you choose to participate in the research, you must sign this form so that your health information may be used for the research.  
| Participant Name:                                   | UAB IRB Protocol Number:  F130515007     |
|-----------------------------------------------------|------------------------------------------|
| Research Protocol: Single Arm Phase II Study of     | Principal Investigator: Ayman Saad, M.D. |
| Myeloablative Allogeneic Hematopoietic Stem Cell    |                                          |
| Transplantation for Acute Lymphoblastic Leukemia    | Sponsor: UAB Comprehensive Cancer Center |
| (ALL) in Older Patients Using Fludarabine and Total |                                          |
| Body Irradiation (FluTBI) Regimen                   |                                          |  
What health information do the researchers want to use? All medical information and personal identifiers, including past, present, and future history, examinations, laboratory results, imaging studies and reports and treatments of whatever kind related to or collected for use in the research protocol. Why do the researchers want my health information? The researchers want to use your health information as part of the research protocol listed above and described to you in the Informed Consent document.  
Who will disclose, use and/or receive my health information? The physicians, nurses and staff working on the research protocol (whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, The Children's Hospital of Alabama, Callahan Eye Foundation Hospital and the Jefferson County Department of Public Health, as necessary for their operations; the IRB and its staff; the sponsor of the research and its employees; and outside regulatory agencies, such as the Food and Drug Administration.  
How will my health information be protected once it is given to others? Your health information that is given to the study sponsor will remain private to the extent possible, even though the study sponsor is not required to follow the federal privacy laws. However, once your information is given to other organizations that are not required to follow federal privacy laws, we cannot assure that the information will remain protected.  
How long will this Authorization last? Your authorization for the uses and disclosures described in this Authorization does not have an expiration date.  
Can I cancel the Authorization? You may cancel this Authorization at any time by notifying the Principal Investigator, in writing, referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and staff will not use any new health information for research. However, researchers may continue to use the health information that was provided before you cancelled your authorization.  
Can I see my health information? You have the right to request to see your health information. However, to ensure the scientific integrity of the research, you will not be able to review the research information until after the research protocol has been completed.  
| Signature of participant: ___                           | Date:   |
|---------------------------------------------------------|---------|
| or participant's legally authorized representative: ___ | Date:   |
| Printed Name of participant's representative:           |         |
| Relationship to the participant: ___                    |         |  
Page 12 of 12
Clinical trial: NCT01991457
Section: Duration of Study Involvement
Subsections: Pre-Transplant (Within 35 Days Prior To Transplant Admission)|Pre-Transplant (Within 14 Days Prior To Transplant Admission)|Transplant Day|Post-Transplant, Reguired Observations And Follow-Up

You will have the following standard evaluations and tests
•
Complete history and physical examination (including blood tests).  
.  
Heart function test (either Echocardiogram or MUGA).  
.  
Lung function test (called Pulmonary Function Tests or PFTs).  
.  
Pregnancy test, if you are a female who could become pregnant.  
.  
Blood sample to check Creatinine, AST, ALT, Alk Phos., and Total bilirubin

.  
You will have a standard procedure called a bone marrow aspirate and biopsy. This is to collect a sample of your bone marrow and evaluate your current disease condition.

On Day 0, the day of your transplant, you will receive your donor stem cell (cells which will eventually develop into white blood cells, red blood cells and platelets). Donor stem cells may be from a donor's blood or bone marrow. Your transplant is performed exactly the same way it would if you are on the study or not.  
After Day 0, you will be given: antibiotics, anti-viral and anti-fungal medication to help prevent infections, or if necessary to fight infections; blood transfusions to increase the number of red blood cells in your system; platelet transfusions to assist in helping your blood to clot; and nutritional and general support, according to the study protocol (and the transplant cnter's institutional guidelines).

Following your transplant you will have regularly scheduled evaluations as part of your standard medical care to monitor your health and how well your transplant has replaced your bone marrow's cells. The follow up visits are scheduled as medically necessary; however, the study will require visits at least once a week visits until day +100 after your transplant.  
From day +100 to one year (day +365) clinic visit will be required at least once per month.  
For this study, you will be followed for 2 years after your transplant, after which followup for your disease is encouraged till at least 5 years post-transplant. The follow-up visits will be determined by your doctors as medically necessary, but with the additional requirements of this study you will have to have the following minimum:  
Acute GVHD (graft-versus-host disease) assessments at least once a week until day +100
.  
and then chronic GVHD assessment at least once per month until 1 year after your transplant.  
•
Immune reconstitution and chimerism studies will be performed. These studies will monitor how well your body cells are recovering.  The recommended timing of the labs is at Day +30 (±7), Day +60 (±7), Day +100 (±14), Day +180 (±21) and at 1 year (±45)
post-transplant.  
At least three bone marrow aspirate and biopsy tests after your transplant, on days +30,
.  
+00, and at 1 year, if your disease has not relapsed (progressed) by that time and you are able to tolerate the procedure. In addition, a marrow aspirate will also be collected whenever a relapse is suspected. Every effort will be made, to do these tests when they are scheduled as part of your standard care.
Your participation in the study will end after the follow-up period is complete 2 years after your transplant.
Clinical trial: NCT01991457
Section: Participant's Rights
Subsections: Information For Women Of Childbearing Potential Or Men Capable Of Fathering A Child|Highly Effective Methods Additional Effective Methods

If you are a female of childbearing age, you must not be pregnant at the time you enter the study, or at any time during the study. This study could potentially harm your unborn child.  
You must avoid becoming pregnant during the study. Before you enter the study, the study doctor will discuss the most appropriate methods to use to avoid pregnancy. All female subjects must commit to using these precautions throughout their participation in the study. If you enter the study and then think you might be pregnant you must tell the study doctor right away. After your participation in the study is complete, if you plan on becoming pregnant you should speak with your study doctor regarding when it is safe to proceed.  
For females, if there is ANY chance that you can get pregnant, you must either agree to not have vaginal intercourse or you must use at least TWO types of birth control (one from each list below or two from the "highly effective" list below)AT THE SAME TIME. You must use two types at the same time for medical reasons. You must talk to the doctor before changing any birth control pills. You should not breastfeed an infant while on the study.

Intrauterine device (IUD)
Latex condom Tubal ligation (Tubes Tied)  
| Diaphragm   |
|-------------|  
Partner's vasectomy Cervical Cap For males, all men must use medically acceptable birth control while taking part in the study, as the effects on sperm are not known. Male patients should not donate blood, semen or sperm during therapy. It is possible you may be a candidate to freeze (cryopreserve) sperm for future use. Discuss this option with the doctor. Cryopreservation is not part of this study.  
Again, all subjects must commit to using these precautions throughout their participation in the study. You should talk to your study doctor so they can advise you, based on the program's clinical practices, when it's safe for you to make any changes.
Clinical trial: NCT01991457
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks And Discomforts

There is a possibility that fludarabine may be less effective than other chemotherapy regimens in treating your disease. The specific medication used in this study and the known side effects which you may experience are listed below:
Clinical trial: NCT01991457
Section: Procedures
Subsections: Explanation Of Procedures|Pre-Transplant, Conditioning Regimen|Drugs For Gvhd (Graft-Versus-Host Disease) Prevention|Drugs For Prevention Of Infection|Fludarabine:|Total Body Irradiation|Anti-Graft-Versus-Host Disease Medications

For your stem cell transplant, you (the recipient) will get FluTBI chemotherapy, followed by an infusion of blood stem cells collected from a donor who is a suitable match. You will have a separate consent form that describes the transplant process and you will be able to ask your doctors and nurses questions about that consent before you make your decision.  
If you decide to take part in this phase 2 clinical research trial you will receive treatment using full-intensity chemotherapy and radiation followed by stem cell transplant. Full intensity means you will receive high doses of chemo-radiotherapy, as a pre-treatment, before your transplant. The high dose chemo-radiotherapy is given to kill as many cancer cells as possible; however it will also destroy your bone marrow's ability to make blood cells. It must be followed by a stem cell transplant to restore your bone marrow function.  
You may be eligible to take part in this research study if your disease is in remission. To be eligible you should meet at least the following inclusion criteria:
40 to 65 years of age. Participants younger than 40 years of age may participate if they have other medical condition which prevents them from participating in more aggressive conditioning regimens.  
.  
You have a suitable donor available, who may be related or unrelated to you.  
.  
Your heart, lung, liver, and kidney function tests are acceptable.  
You must be well enough to undergo full intensity conditioning
There are conditions that might exclude you. If you are HIV positive, or have any active infections, for example, you would not be eligible for this study. If female, you cannot be pregnant or breastfeeding. You may not take part if you have another active life threatening cancer that requires treatment other than stem cell transplant or if your disease involves the central nervous system (CNS), which is your brain and spinal cord. Your research doctor will review with you in more detail the eligibility criteria that may apply to you.  
If you decide to participate in this study you will receive FluTBI as your chemotherapy regimen starting 7 days before your transplant. You and your study doctors and nurses will review the clinical information for the transplant. In preparation to receive your stem cell transplant the following test will be performed as transplant standard of care whether you are on the study or not. We will use the information from your medical record to evaluate this trial oly if you decide to participate.

In this research study, subjects enrolled will receive the FluTBI pre-treatment (the conditioning regimen) beginning with Fludarabine for 4 days. Each day's total Fludarabine dose is given on Days -7 to -4, prior to your transplant on Day 0. You will receive Total Body Irradiation (TBI) for 3 days. Total dose of TBI is given on Days -3 to -1, prior to your transplant on Day 0. The FluTBI treatment is summarized in the following table.  
| Chemotherapy drugs-FluTBI                                                                       |                               |                        |
|-------------------------------------------------------------------------------------------------|-------------------------------|------------------------|
| Day, Pre-Transplant                                                                             | Fludarabine                   | Total Body Irradiation |
| Day -7                                                                                          | 1st dose IV                   |                        |
| 2" dose IV                                                                                      |                               |                        |
| Day -6                                                                                          |                               |                        |
| Day -5                                                                                          | dose IV                       |                        |
| 3                                                                                               |                               |                        |
| Day -4                                                                                          | dose IV                       | 1 st dose              |
| Day -3                                                                                          |                               |                        |
| Day -2                                                                                          | 2" dose                       |                        |
| 3" dose                                                                                         |                               |                        |
| Day -1                                                                                          |                               |                        |
| Day 0                                                                                           | Transplant-Stem cell infusion |                        |
| You will receive medication according to the center's institutional guidelines to helps relieve |                               |                        |  
some of the side effects of chemo-radiotherapy.

GVHD is where the donor stem cells treat the recipient's body as "foreign" and attack clls in the recipient's body. GVHD is one of the common complications with allogeneic stem cll transplant, (where you receive cells from another person). It can affect organ tissues such as skin, stomach, intestines, lungs, liver and others.  
The following drugs, thymoglobulin, (rATG), Atgam, methotrexate, tacrolimus and Leucovorin are permitted under the protocol. Your study doctor may prescribe any of combination of these drugs to try to prevent GVHD (GVHD prophylaxis), or help reduce its severity if you do develop GVHD. The specific drugs that you receive will depend on both your study doctors' judgment for what is best for you and the transplant center's standard medical practice

After your transplant, your immune system is severely weakened and slowly improves over many weeks or months. There are a number of different drugs available that your study doctor may prescribe to try to prevent infections. The specific drugs that you receive will depend on both your study doctors' judgment for what is best for you and your transplant's standard medical practices.

Drug-related side effects observed in more than 10% of adult patients treated with Fludarabine in previous clinical trials include decreased bone marrow function
(myelosuppression), fever and chills, infections, nausea and vomiting, pain, weakness, cough, pneumonia, (shortness of breath) dyspnea, diarrhea, anorexia, rash, edema.  
Side effects observed in less than 10% of adult patients (general weakness) malaise,
(oral inflammation) stomatitis, (muscle pain) myalgia, (abnormal sensations) paresthesia, visual disturbance, gastrointestinal bleeding, upper respiratory infection, (excessive sweating)
diaphoresis, (painful urination) dysuria, urinary infection, sinusitis, hearing loss, hyperglycemia, headache, (sore throat) pharyngitis, (spitting blood) hemoptysis, (swelling of the esophagus) esophagitis, mucositis, (blood in urine) hematuria, osteoporosis, (hair loss) alopecia, (serious allergic reaction) anaphylaxis, hemorrhage, dehydration, sleep disorder, depression, (lack of coordination) cerebellar syndrome, impaired mentation, allergic pneumonitis, (nose bleeds)
epistaxis, bronchitis, hypoxia, liver failure, abnormal liver function, (gallstones) cholelithiasis, ARDS, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, respiratory failure, constipation, dysphagia, (itching) pruritus, (dandruff) seborrhea, renal failure, abnormal renal function test, (protein in urine) proteinuria, hesitancy, angina, congestive heart failure, arrhythmia, (rapid heart rate) supraventricular tachycardia, myocardial infarction, deep venous thrombosis, (swelling of a vein) phlebitis, transient ischemic attack, aneurysm, (stroke)
cerebrovascular accident, (joint pain) arthralgia, tumor lysis syndrome.

Possible side effects of total body radiation include; loss of appetite, nausea, vomiting, diarrhea, (dry mouth) xerostomia, (difficulty in swallowing) dysphagia, headache, (swelling in the mouth/throat) stomatitis, altered skin integrity, (hair loss) alopecia, swelling, increased risk for infection and/or bleeding, possible lung failure, dry cough, fatigue, anxiety, fever, possible liver failure, lung scarring, loss of vision, shortness of breath, (permanent dilation of small vessels causing red lesions) telangiectasia, testicular damage, ovarian damage, premature menopause, sterility, heartburn, cystitis, sleep disturbances altered gastrointestinal and genitourinary function,  radiation pneumonitis, neuropathy, fistulas, altered endocrine function, and increased risk of a second cancer.

GVHD is due to immune cells (lymphocytes) from the donor attacking the recipient's organs. The acute form of GVHD may cause redness of the skin, nausea, vomiting, diarrhea, and/or liver problems. The chronic form of GVHD may cause dryness of the eyes and/or mouth, and/or breathing problems. It may cause tightness and/or scarring of the skin, weight loss, diarrhea, and/or difficulty swallowing. Either one of the forms of GVHD can range from mild to severe to life threatening. Severe GVHD is commonly the cause of death for patients who have serious and fatal complications, after their transplant.  
During your transplant process you will receive standard of care medications to help prevent and/or decrease GVHD. These are listed in the tables below.  
| Tacrolimus                                                                                | Rare, but Serious                |                                     |                        |                |                          |
|-------------------------------------------------------------------------------------------|----------------------------------|-------------------------------------|------------------------|----------------|--------------------------|
| Likely                                                                                    | Less likely                      | (These possible risks have been     |                        |                |                          |
| ("Likely" refers to a side effect                                                         | ("Less likely" refers to a side  | reported in rare occurrences,       |                        |                |                          |
| that is expected to occur in more                                                         | effect that is expected to occur | typically less than 2% of patients. |                        |                |                          |
| than 20% of patients.)                                                                    | in 20% or fewer patients.)       | They may be serious if they         |                        |                |                          |
| occur.)                                                                                   |                                  |                                     |                        |                |                          |
| .                                                                                         | Low red blood cell               | .                                   | Hair loss              | .              | Confusion                |
| counts                                                                                    | -                                | Vomiting                            | -                      | Painful joints |                          |
| .                                                                                         | Loss of appetite                 | .                                   | Tingling sensation in  | .              | Increased sensitivity to |
| .                                                                                         | Diarrhea                         | the extremities                     | light                  |                |                          |
| .                                                                                         | High potassium levels            | -                                   | Itching                | .              | Blurred vision           |
| -                                                                                         | High blood pressure              | -                                   | Rash                   | .              | Insomnia(unable to       |
| .                                                                                         | Nausea                           | .                                   | Abdominal pain         | sleep)         |                          |
| .                                                                                         | Fever                            | .                                   | Jaundice (yellowing of |                |                          |
| .                                                                                         | Headache                         | skin and eyes)                      |                        |                |                          |
| High blood sugar                                                                          | Kidney injury                    |                                     |                        |                |                          |
| .                                                                                         | -                                | seizures                            |                        |                |                          |
| These side effects are usually reversible by reducing the dose or discontinuing the drug. |                                  |                                     |                        |                |                          |  
| Methotrexate                                                   | Rare, but Serious                              |                                     |                                |           |           |
|----------------------------------------------------------------|------------------------------------------------|-------------------------------------|--------------------------------|-----------|-----------|
| Likely                                                         | Less likely                                    | (These possible risks have been     |                                |           |           |
| ("Likely" refers to a side effect                              | ("Less likely" refers to a side                | reported in rare occurrences,       |                                |           |           |
| that is expected to occur in more                              | effect that is expected to occur in            | typically less than 2% of patients. |                                |           |           |
| than 20% of patients.)                                         | 2% or fewer patients.)                         | They may be serious if they         |                                |           |           |
| occur.)                                                        |                                                |                                     |                                |           |           |
| .                                                              | High levels of liver                           | .                                   | Nausea                         | .         | Hair loss |
| enzymes                                                        | .                                              | Vomiting                            | .                              | Dizziness |           |
| .                                                              | Loss of appetite                               | .                                   | Skin redness,                  |           |           |
| .                                                              | Diarrhea                                       | tenderness, darkening,              |                                |           |           |
| Mouth sores                                                    | and peeling                                    |                                     |                                |           |           |
| .                                                              | Sensitivity to sunlight                        | -                                   | Blurred vision                 |           |           |
| .                                                              | Increased risk of                              | -                                   | Allergic reaction              |           |           |
| -                                                              | sunburns                                       | .                                   | Damage to nerve tissue         |           |           |
| Decrease number of red                                         | Kidney damage                                  |                                     |                                |           |           |
| .                                                              | .                                              |                                     |                                |           |           |
| and white blood cells                                          | Seizures                                       |                                     |                                |           |           |
| .                                                              |                                                |                                     |                                |           |           |
| and platelets                                                  | .                                              | Decreased lung function             |                                |           |           |
| -                                                              | Decreased liver                                |                                     |                                |           |           |
| function- temporary                                            |                                                |                                     |                                |           |           |
| -                                                              | Bone and tissue damage                         |                                     |                                |           |           |
| -                                                              | Loss of memory,                                |                                     |                                |           |           |
| concentration, balance,                                        |                                                |                                     |                                |           |           |
| and walking                                                    |                                                |                                     |                                |           |           |
| Thymoglobulin                                                  | Less likely but Serious                        |                                     |                                |           |           |
| Likely                                                         | ("Less likely" refers to a side effect that is |                                     |                                |           |           |
| ("Likely" refers to a side effect that is expected to occur in | expected to occur in 25% or fewer              |                                     |                                |           |           |
| more than 25% of patients.)                                    | patients.)                                     |                                     |                                |           |           |
| .                                                              | fever                                          | .                                   | Severe or life threatening     |           |           |
| .                                                              | chills                                         | allergic reaction                   |                                |           |           |
| .                                                              | decreased platelets and white blood cells      | .                                   | Lymphomas (i.e. cancers of the |           |           |
| .                                                              | pain                                           | immune system)                      |                                |           |           |
| .                                                              | headache                                       |                                     |                                |           |           |
| .                                                              | abdominal pain,                                |                                     |                                |           |           |
| diarrhea                                                       |                                                |                                     |                                |           |           |
| .                                                              | high blood pressure                            |                                     |                                |           |           |
| .                                                              | n nusea                                        |                                     |                                |           |           |
| .                                                              | swelling                                       |                                     |                                |           |           |
| .                                                              |                                                |                                     |                                |           |           |
| .                                                              | difficulty breathing                           |                                     |                                |           |           |
| .                                                              | weakness                                       |                                     |                                |           |           |
| .                                                              | high potassium                                 |                                     |                                |           |           |
| .                                                              | rapid heartbeat                                |                                     |                                |           |           |
| -                                                              | infection                                      |                                     |                                |           |           |  
Page 7 of 12
Clinical trial: NCT01991457
Section: Purpose of Research
Subsections: Purpose Of The Research

You are being invited to participate in this research trial because you are going to receive a stem cell transplant from a matched brother or sister, or an unrelated donor to treat your leukemia. The goal of this research is to evaluate a pre-transplant (conditioning) regimen for stem cell transplant patients with high-risk disease that provides an anti-leukemia effect with fewer side effects. The conditioning regimen being used in this trial is the drug Fludarabine and Total Body Irradiation (FluTBI). The use of FluTBI for cancer treatment has been approved by the FDA (U.S. Food and Drug Administration). We are studying the combination of fludarabine and total body irradiation in stem cell transplant patients which has not been FDA approved.  
Many transplant centers use full intensity conditioning treatments such as CyTBI
(Cyclophosphamide and Total body Irradiation) as a standard pre-treatment for transplantation, but severe drug-related side effects remain a major cause of death. Fludarabine, though less effective when compared to Cyclophosphamide, has less drug-related side-effects. Fewer drug related side effects is a potential benefit for patients who are older or have high-risk disease.  
This study will continue to test if this new conditioning treatment, FluTBI, can lead to a safer and more effective stem cell transplant treatment approach for patients 40 to 65 years of UAB IRB
A / G / /
age and/or younger patients with high risk disease. This is a phase II clinical trial that will enroll approximately 20 patients, all of whom will be enrolled at UAB. You will be followed for a minimum of 2 years after your transplant as part of this study; this is the same transplant follow-up as you would have whether you are on the study or not on the study.
Clinical trial: NCT01991457
Section: Voluntary Participation
Subsections: Voluntary Participation And Withdrawal

Taking part in this study is completely voluntary. You do not have to participate if you don't want to. You may also leave the study at any time. If you leave the study before it is finished, there will be no penalty to you, and you will not lose any benefits to which you are otherwise entitled.  
You are free to withdraw from this research study at any time. Your choice to leave the study will not affect your relationship with this institution. However, you should return to see the study doctor for safety reasons so you can be taken off the study drugs and referred for follow-up care.  
You may be removed from the study without your consent if the investigator ends the study,  if the study doctor decides it is not in the best interest of your health, or if you are not following the study rules.  
As a rule, the researchers will not continue to use or disclose information about you, but will keep it secure until it is destroyed.  Sometimes, it may be necessary for information about you to continue to be used or disclosed, even after you have canceled your permission or the study is over.  
You may withdraw your consent by writing the BMT research Office at UAB BMT
Research office-West Pavilion Room 392-619 19th Street South - Birmingham, AL 35249-6979.