IRB Number:

07-001085

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Patients are being asked to take part in this research study because their doctor has tested the patient's blood and/or bone marrow and determined that they have a diagnosis of relapsed Chronic Lymphocytic Leukemia (CLL). The purpose of the study is to compare the clinical benefit of Lumiliximab in combination with Fludarabine, Cyclophosphamide, and Rituximab (FCR) to FCR alone and to compare the safety of Lumiliximab when given in combination with FCR to FCR alone. This will include looking at what side effects occur and how often they occur.
Lumiliximab is an investigational drug made by Biogen Idec Inc. (Biogen Idec) that is
being studied for the treatment of relapsed chronic lymphocytic leukemia (CLL). Regulatory authorities have not yet approved lumiliximab for general use, but they have allowed it for use in clinical trials. Lumiliximab is a monoclonal antibody made of monkey and human proteins. A monoclonal antibody is a substance made in the laboratory that binds to a specific protein. Although doctors don't know exactly how lumiliximab works, it is believed that lumiliximab binds to a protein on CLL cells and causes them to die.
At the time of this summary, a total of 257 patients have received lumiliximab. This includes patients with CLL as well as patients with allergic disorders. In clinical trials in patients with CLL, lumiliximab has been given alone as well as with fludarabine, cyclophosphamide, and rituximab (FCR), a drug combination frequently used to treat people with CLL.
Fludarabine is a type of chemotherapy drug, which has been approved for the treatment of patients with CLL. Cyclophosphamide is another approved chemotherapy drug often given with fludarabine. Rituximab is a monoclonal antibody made of mouse and human proteins. It attaches to a specific protein found on most CLL cells. Rituximab has been approved in the US, Canada, and Europe for the treatment of some cancers. Although rituximab is commonly used for the treatment of CLL, it has not been approved for this disease.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with relapsed B-cell Chronic Lymphocytic Leukemia (CLL)
-Received no more than two prior single agent or combination treatments for disease

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

If agreeing to be in the study, patients will be asked to participate in the following:

For the purposes of this document, study drug will refer to lumiliximab in combination with FCR or FCR alone.

Clinic Visits
If deciding to be in this study, patients agree to come to the clinic for as many as three screening visits, about 24 treatment visits, and 12 follow-up visits, for a total of about 39 visits over four years or until their disease progresses and they require another CLL therapy. The maximum time that the patient will be involved in this study is four years. However, their disease may be followed for the rest of their life.

Trained study staff will:
- Talk to the patient about the study in greater detail.
- Perform all study visit procedures.
- Administer the study treatment.

The study staff may also perform more tests and evaluations if they feel that they are needed for the patient's safety or well-being.

Screening Visits
If agreeing to be in this study, the study staff will complete the following tests and procedures during a screening period to determine if the patient can take part in this study. This screening period will last about 30 days.
- Patients will be asked about their health problems, including past surgeries and past treatments for CLL.
- They will be asked about medications that they are currently taking, including over-thecounter medications, herbal remedies, vitamins, and supplements.
- Patients will have a physical examination, which will include measuring their temperature, blood pressure, height, weight, heart rate, breathing rate, and health status. It will also include measurements of their spleen, liver, and lymph nodes.
- Patients will be asked about any disease-related symptoms they are experiencing.
- Patients will be asked to complete questionnaires about their general health and well-being. There are two questionnaires they will be asked to complete while taking part in this study, the EQ-5D Health Questionnaire and the FACT-G questionnaire. The patient will be asked to complete these questionnaires at their screening visit, week 13 visit, week 25 visit, month 12 visit, month 36 visit and month 48 visit for a total of seven times.
- Patients will have a chest x-ray and an ECG. An ECG is an electrocardiogram. It measures the electrical activity of the heart.
- If the patient has had a therapy since their last biopsy, they may be asked to have a bone marrow biopsy before treatment to confirm that they have CLL. Bone marrow is the
spongy material found inside a person's bones. CLL can spread to the bone marrow or start in the bone marrow. Doctors may examine part of the marrow to see whether cancer is present.
- Patients will have a computed tomography (CT) scan of their chest, abdomen and pelvis, including the neck if needed. A CT scan uses special x-ray equipment to take pictures of the body and will be used to evaluate the patient's disease.
- A small sample of the patient's blood will be collected. This blood will be collected for routine safety blood tests and for other specialized laboratory tests that are for research purposes.
- Patients will be asked to provide a urine sample for routine safety urine tests.
- Patients will have a pregnancy test if they are a woman able to become pregnant.

If eligible to take part in the study, patients will be asked to return to the clinic to receive their first dose of study treatment. If they are not eligible, the study staff will discuss other treatment options with the patient.

Treatment Visits
Patients will have about 24 treatment visits over six months. They will receive treatment for three days about every four weeks, which is one cycle of treatment. The patient will receive up to six cycles of treatment. They will return to the clinic every two weeks for follow-up.

On Study Day 1 of Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 the following procedures will be performed:

- Patients will be asked about medications they are currently taking, including over-the-counter medications, herbal remedies, vitamins, and supplements
- Patients will be asked about any new or continuing side effects or illnesses they have had since their last visit.
- Patients will have a physical examination, which will include measuring their temperature, blood pressure, weight, heart rate, breathing rate, and health status.
- A sample of their blood will be collected. This blood will be tested for routine safety blood tests, to measure the level of drug in the patient's blood and for other specialized laboratory tests that are for research purposes. A small sample of blood will also be collected on Study Day 4 of Week 1. This blood is for specialized laboratory tests that are for research purposes.
- Patients will be asked to complete questionnaires about their general health and well-being on Day 1 of Week 13 (Cycle 4).

On days when the patient will receive the study treatment, Days 1, 2, 3 and 4 of Cycle 1 (Week 1) and Days 1, 2, and 3 of Cycles 2 to 6 (Weeks 5, 9, 13, 17, and 21):

- Patients will receive antibiotics and antiviral treatments to help reduce the risk of infections, as well as allopurinol and hydration to prevent other side effects throughout the treatment period.
- Patients will receive acetaminophen or its equivalent and diphenhydramine HCL approximately 30 minutes before each of the infusions of lumiliximab and rituximab to help prevent potential side effects during the infusion.
- Patients may also receive a medicine to prevent nausea and vomiting.

Treatment Group A (Lumiliximab plus FCR)
Cycle 1 (Week 1)
Day 1 - Patients will receive the first infusion of rituximab into a vein over a period of approximately four hours; this first infusion may require a longer period of time than the remaining infusions.
Day 2 - Patients will receive the first infusion of lumiliximab into a vein over a period of four hours; this first infusion may require a longer period of time than the
remaining infusions.
Day 3 - Patients will receive the second part of the first infusion of rituximab into a vein over a period of approximately four hours.
Day 4 - Patients will receive the second part of the first infusion of lumiliximab into a vein over a period of approximately four hours.
Days 2, 3, and 4 - Patients will receive fludarabine and cyclophosphamide injections over 10 to 30 minutes.

Cycles 2 through 6 (Weeks 5, 9, 13, 17, and 21)
Day 1 - Patients will receive the infusion of rituximab over a period of approximately four hours.
Day 1 - Patients will receive the infusion of lumiliximab over a period of approximately two hours.
Days 1, 2, and 3 - Patients will receive fludarabine and cyclophosphamide injections over 10 to 30 minutes.

Treatment Group B (FCR alone)
Cycle 1 (Week 1)
Day 1 - Patients will receive the first infusion of rituximab into a vein over a period of approximately four hours; this first infusion may require a longer period of time than the remaining infusions.
Day 3 - Patients will receive the second part of the first infusion of rituximab into a vein over a period of approximately four hours.
Days 2, 3, and 4 - Patients will receive fludarabine and cyclophosphamide injections over 10 to 30 minutes.

Cycles 2 through 6 (Weeks 5, 9, 13, 17, and 21)
Day 1 - Patients will receive the infusion of rituximab over a period of approximately four hours.
Days 1, 2, and 3 - Patients will receive fludarabine and cyclophosphamide injections over 10 to 30 minutes.
- During the time the patient is receiving the study treatment, their temperature, pulse, blood pressure, and breathing will be carefully watched, and they will be treated for any side effects they may have. If the patient has certain side effects, their doctor may slow down or stop the infusion of the study treatment.
- If the patient has a high white blood cell count or if their study doctor feels this is necessary, the rituximab and lumiliximab (if applicable) infusions during Cycles 2 to 6 will be split over Day 1 and Day 2, as in the first cycle. This will be done to minimize potential infusion reactions.
- Fludarabine and cyclophosphamide may be given over greater than 30 minutes if this is the normal practice of the clinic. The study doctor will be able to provide the patient with further information.
- The study doctor will determine the patient's response to treatment. This will be based on the information gathered and includes spleen, liver, and lymph node measurements,
and an evaluation of the patient's disease-related symptoms. A bone marrow biopsy and aspirate will be taken if the study doctor feels it is necessary to evaluate the patient's response or the recurrence of their disease.
- Patients will be asked to complete questionnaires about their general health and well-being

(Week 13).
Follow-Up Visits
Patients will have 12 follow-up visits over four years.
On Study Weeks 25, 29, 33, at the time a complete response to study drug is confirmed and Study Months 12, 15, 18, 21, 24, 30, 36, 42, and 48, patients will have the following
procedures performed:
- Patients will have a CT scan of their chest, abdomen and pelvis (including the neck if needed) to evaluate their disease if they are responding to the study drug (at the time a complete response is confirmed and at Months 12, 18, 24, and 30).
- Patients will have a physical examination, which will include measuring their temperature, blood pressure, weight, heart rate, breathing rate, and health status.
- Patients will be asked about medications that they are currently taking, including over-thecounter medications, herbal remedies, vitamins, and supplements.
- A small sample of the patient's blood will be collected. This blood will be collected for routine safety blood tests and for other specialized laboratory tests that are for research purposes.
- Patients will be asked to provide a urine sample for routine safety urine tests (Week 25, Month 12, and Month 48).
- Patients will be asked about any side effects or illnesses since their last visit.
- The study doctor will determine the patient's response to treatment. This will be based on the information gathered and includes spleen, liver, and lymph node measurements,
and an evaluation of their disease-related symptoms. A bone marrow biopsy and
aspirate will be taken if the study doctor feels it is necessary to evaluate the patient's
response or the recurrence of their disease.
- Patients will be asked to complete questionnaires about their general health and well-being

(Week 25 and Months 12, 24, 36, and 48).
After month 48, the study doctor or study staff may contact the patient (about every six months) to find out the status of their CLL when they are no longer coming to the clinic for study visits.

Patients will be put in one of two groups by chance (as in the flip of a coin). The two groups are receiving either lumiliximab in combination with FCR (Treatment Group A) or FCR alone (Treatment Group B). This is an open-label study. The patient, their study doctor, and the study staff will know whether the patient is receiving lumiliximab in combination with FCR or FCR alone.

The drug (lumiliximab) used in this study is considered investigational, which means it has either not been approved by the U.S. Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug in this research study.

How long will the Study run?

Patients will be in the study for the rest of their life.

Sponsor(s): Biogen IDEC

Study Activation/Registration Date: 08/24/2007

IRB Review and Approval Date: 06/13/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 276 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Craig B. Reeder, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Scottsdale and Phoenix, AZ

Last updated: 05/14/2008