Clinical trial: NCT00924170
Section: Alternatives
Subsections: Alternative Approaches Or Treatments

You may decide now not to receive treatment in this protocol or you may choose at any point in time to stop the drug and withdraw from the protocol. In either case you would be returned to the care of your referring physician.  
Because of the type and extent of your tumor, chemotherapy is felt to be more beneficial than surgery or radiation alone. Alternative approaches that could be used may include:
1. Other forms of treatment:
a. Additional chemotherapy drugs and chemotherapy drug combinations which might be of benefit for your disease.  
PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study  
NIH-2977 (4-17)  
File in Section 4: Protocol Consent (2)  
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b. Radiation treatment, which sometimes can control tumor growth in local areas such as lymph nodes, spleen and bones. However, this approach will not effectively treat disease that has spread beyond the areas that are irradiated.
Clinical trial: NCT00924170
Section: Confidentiality
Subsections: Confidentiality Protections Provided In This Study Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality|Privacy Act

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
- The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.  
- National Institutes of Health Intramural Institutional Review Board The researchers conducting this study and the NIH follow applicable laws and policies to keep your identifying information private to the extent possible. However, there is always a chance that, despite our best efforts, your identity and/or information about your participation in this research may be inadvertently released or improperly accessed by unauthorized persons.  
In most cases, the NIH will not release any identifiable information collected about you without your written permission. However, your information may be shared as described in the section of this document on sharing of specimens and data, and as further outlined in the following sections.  
Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.

To help us protect your privacy, the NIH Intramural Program has received a Certificate of Confidentiality (Certificate). With this certificate, researchers may not release or use data or information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a court. The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used for auditing or program evaluation internally by the NIH; or 2. is required to be disclosed by Federal, State, or local laws, for example, when information must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA);
3. is for other research; 4. is disclosed with your consent.  
The Certificate does not prevent you from voluntarily releasing information about yourself or your involvement in this research.  
PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study  
NIH-2977 (4-17)  
File in Section 4: Protocol Consent (2)  
Version Date: 03/01/2021 **a.\** IRB NUMBER: 09C0025  
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The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or others including, for example, child abuse and neglect, and by signing below you consent to those disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice and Acknowledgement of Information Practices consent.

The Federal Privacy Act generally protects the confidentiality of your NIH medical records we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your medical record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
Clinical trial: NCT00924170
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Cyclophosphamide Toxicity|Fludarabine Toxicity|Toxicity Of Filgrastim (G-Csf)|Risks Associated With Routine Procedures Blood Drawing|What Are The Risks Of Radiation From Research?|Potential Benefits Of Participation

Administration ofFC and LMB-2 will be through a central venous catheter (CVC) or a peripheral I.V. The CVC is inserted by experienced staff using local anesthesia. The risks associated with the procedure include pain, bleeding, infection, and development of air in the chest. However, these complications are rare. Air in the chest outside the lung may require temporary placement of a chest tube by a surgeon. The risks of chest tube placement include pain, bleeding, and infection. Other risks of the catheter include infection and clotting of your veins, which could require removal of the catheter for treatment. These risks will be explained to you in more detail at the time of insertion. When a peripheral line is used, there is a small risk of infection, clot or bleeding at the site of the IV line. There is also a risk of some of the drug leaking out, also called extravasating. If that occurs there may be some destruction of skin tissue in a limited area. Patients are urged to alert the study physicians at the first sign of any skin changes, for example redness or tenderness, around the infusion site but also with any discomfort in the involved extremity as well.  
If there is any evidence of toxicity from leaking, the infusion will be held until a central line can be placed for the infusion of drug. In addition, any toxic effects to the skin will be treated to the fullest extent possible.

a. Nausea and vomiting - variable; can be improved with standard medications ( e.g., lorazepam).  
b. Water retention - cyclophosphamide inside the body may turn into a drug which can hurt the kidney. This side effect can be counteracted by a diuretic called furosemide.  
c. Cardiomyopathy - cyclophosphamide may cause severe, sometimes fatal, heart damage.  
Patients may present with heart failure as late as 2 weeks after the last dose of cyclophosphamide. The clinical syndrome has been observed mainly in patients receiving a higher dose of cyclophosphamide (1200 mg/m2) used in transplant protocols.
d. Hemorrhagic cystitis - this is a serious, potentially life-threatening complication to the bladder.  
Although unnoticeable blood in the urine is not uncommon at this dose level, clinically significant blood in the urine can usually be avoided by maintaining a high urine volume and frequently urinating. The patient is encouraged to drink plenty of fluids, at least 2 liters per day, while taking FC.  
e. Sterility
f. Less common but serious complications include lung damage and new cancers. Less common but temporary toxicities include balding and skin rash.

Fludarabine toxicities include bone marrow damage with low blood counts, fever, nausea, vomiting, sores in the mouth, diarrhea, stomach bleeding, low appetite, swelling, skin rashes, muscle aches, headache, nervousness, hearing loss, temporary episodes of fatigue, destruction of red cells and platelets by the body's immune system, abnormal sensations, kidney damage, and lung damage. Severe fatal brain toxicity with loss of vision and progressive deterioration of mental status were seen almost exclusively after very high doses of fludarabine. This toxicity has only  
PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study  
NIH-2977 (4-17)  
File in Section 4: Protocol Consent (2)  
Version Date: 03/01/2021 **a.\** IRB NUMBER: 09C0025  
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rarely been seen at the dosage of fludarabine used for this trial. Very rarely described complications include severe autoimmune disease and liver failure. Tumor lysis syndrome following fludarabine administration has been observed, especially in patients with advanced bulky tumors. The symptoms of tumor lysis syndrome include rapid reduction in tumor size, fever, low blood pressure, abnormal blood chemistry results, and decreased kidney function. Unusual infections seen in immunosuppressed people (protozoan, viral, fungal, and bacterial) have been observed after-fludarabine, especially in heavily pre-treated patients, and in patients receiving fludarabine combined with other agents.  
Patients with lymphoma and leukemia often have low blood counts and require red blood cell and/or platelet transfusions, with associated risks including transfusion reactions and infections
(such as HIV and hepatitis). Prior treatment may have weakened your immune system. It is possible that LMB-2 may also weaken your immune system. Infections that develop in individuals with cancer can be very serious. You should seek immediate medical attention for fever greater than or equal to 100 degrees or any signs of infection.

Filgrastim can cause skin rash, muscle and/or bone pain, an increase in any inflammatory conditions which you had before, like arthritis, enlarged spleen possibly causing a lowering of the platelet count, and abnormal blood chemistry levels. Loss of hair can occur with prolonged use.  
Summary of severe toxicity of FC chemotherapy and antibody therapy:
- Likely (50-75% of patients): Low neutrophils - Less Likely (25-50% of patients): Low platelets - Unlikely (10-25% of patients): Infections including pneumonia

To monitor the effects of therapy frequent blood tests will be necessary. Up to a one unit (about 50 teaspoons) of blood, may be drawn every 4 weeks while you are participating in the study and up 2 tablespoons of blood may be collected every 6 months during each follow-up visit for research purposes. Every effort will be made to keep blood tests to a minimum. You will be monitored for anemia and given blood transfusions if needed. Side effects of blood draws include pain and bruising in the area where the needle was placed, lightheadedness, and rarely, fainting.  
Urine Collection There is no risk related to urine collection.  
Medical photography There are no risks associated with medical photography.  
PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study  
NIH-2977 (4-17)  
File in Section 4: Protocol Consent (2)  
Version Date: 03/01/2021 **a.\** IRB NUMBER: 09C0025  
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Bone Marrow Testslf a bone marrow aspiration is done, your hipbone will be numbed with anesthesia, a small needle will be inserted into the hipbone, and about two tablespoons of bone marrow will be removed through the needle. This procedure usually causes only brief discomfort.  
Very rarely, infection or bleeding may occur at the needle site.

During your participation in this research study, you may be exposed to radiation from up to 2 CT
scans and up to 2 PET/CT scans each year. The amount of radiation exposure from these procedures is equal to approximately 5 rem. A rem is a unit of absorbed radiation.  
Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation."
No one knows for sure whether exposure to these low amounts of radiation is harmful to your body.  
The CT and PET/CT scans that you get in this study will expose you to the roughly the same amount of radiation as 16. 7 years' worth of background radiation. Most of the time, this amount of extra radiation is not harmful to you. However, scientists believe that being exposed to too much radiation can cause harmful side effects. This could include getting a new cancer. We estimate that this could happen in about 1 out of every 1000 people who get a very large amount of extra radiation.  
You may not participate in this study if you are pregnant. If you are able to become pregnant, we will perform a pregnancy test before exposing you to radiation. You must tell us if you may have  
PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study  
NIH-2977 (4-17)  
File in Section 4: Protocol Consent (2)  
Version Date: 03/01/2021 **a.\** IRB NUMBER: 09C0025  
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become pregnant within the previous 14 days because the pregnancy test is unreliable during that time.

While we hope that LMB-2 treatment will be beneficial to you, you may not benefit from this treatment. LMB-2 treatment may cause improvement in your leukemia such as reduction in cancer-related symptoms. Your participation in this study may help us advance the understanding of the use of biologic agents in the treatment of leukemia and lymphoma.
Clinical trial: NCT00924170
Section: Purpose of Research
Subsections: Why Is This Study Being Done? Description Of Research Study

This is a clinical trial for the treatment of adult T-Cell leukemia with an experimental drug called LMB-2 after the combination of the chemotherapy drugs fludarabine and cyclophosphamide (FC).  
The 2 drugs in addition to LMB-2 are abbreviated FC. You will be treated with FC on days 1, 2, PATIENT IDENTIFICATION Consent to Participate in a Clinical Research Study NIH-2977 (4-17)
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and day 3 for each of 7 cycles. The beginning of the 2nd cycle is about 2 weeks after first, and after that the cycles are about 3 weeks apart. Starting with the 2nd cycle, on the last day of FC ( day 3),
you will be treated with LMB-2 every other day for 3 doses. After this 2nd cycle, you can be retreated with FC/LMB-2 a maximum of 5 more times provided certain requirements are met.  
LMB-2 is a recombinant immunotoxin that has been shown to kill leukemia and lymphoma cancer cells that have a protein on their surface called "CD25". To be eligible for treatment on this study, your malignant cells must have CD25 on their surface. However, the presence of CD25 on your malignant cells does not guarantee that you will be enrolled on the protocol. We plan to include at most 3 7 patients on this trial.  
LMB-2 is an experimental drug called a recombinant immunotoxin. Each LMB-2 molecule is made up of two parts: a protein part that binds or targets a cancer cell and a toxin (a type of poison)
part that goes inside and kills the cancer cell. The binding part is part of an antibody that binds to human CD25, a protein on your leukemia or lymphoma cells. The toxin portion of LMB-2 is naturally produced by bacteria. In laboratory experiments using leukemia or lymphoma cells outside the body, LMB-2 kills cells which have CD25 on their surface. LMB-2 also causes a significant decrease in the size of tumors in mice that were given doses similar to those used in the first human trial ofLMB-2.  
A preliminary study of LMB-2 has been performed at the National Cancer Institute (NCI) in which 39 patients with various leukemias and lymphomas were treated. In that trial, patients with hairy cell leukemia ( 4 patients), cutaneous T cell lymphoma ( 1 ), adult T-cell leukemia/lymphoma ( 1 ),
Hodgkin's disease (1) and chronic lymphocytic leukemia (1) had reduction in their tumors.
Clinical trial: NCT00924170
Section: Voluntary Participation
Subsections: It Is Your Choice To Take Part In The Study

You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.
Clinical trial: NCT00924170
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:  
- if he/she believes that it is in your best interest
- if your disease comes back during treatment - if you have side effects from the treatment that your doctor thinks are too severe - if new information shows that another treatment would be better for you
In this case, you will be informed of the reason therapy is being stopped.  
You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first.  
If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to NCI or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases **cannot** be recalled and destroyed.