IRB Number:

07-004603

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Patients are being asked to take part in this research study to test whether a new drug called SGN-40, added to a commonly used drug combination of antibody (rituximab) and chemotherapy drugs (ifosfamide, carboplatin, and etoposide) called R-ICE, is safe and will improve the outcome for participants with diffuse large B-cell lymphoma (DLBCL) that has relapsed or failed to go away completely after initial treatment.
SGN-40 is a type of drug called a monoclonal antibody (the same type of drug as Rituxan or Mab Thera, which patients have previously received). Monoclonal antibodies are proteins that are designed to attack specific targets on cells. SGN-40 is an antibody which is made from human protein and reacts with a target, CD40, on white blood cells and tumor cells. CD40 is found on almost all DLBCL tumors.

Who is Eligible to Participate in the Study?

-Patient is at least 18 years old and no more than 75 years old
-Diagnosed with diffuse large B-cell lymphoma (DLBCL)
-Received at least four cycles of first-line therapy with R-CHOP or equivalent first line therapy including rituximab, cyclophosphamide, anthracycline or anthracenedione and steroid with or without additional chemotherapy agent(s).

*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:
This study consists of three phases:

- Evaluation phase: Patients will have tests to see whether they are eligible to participate. In most cases this will take a few days to complete but could last
up to several weeks.

- Treatment phase: Patients will receive R-ICE and study drug for three cycles of three weeks each (nine weeks total). When the treatment period is finished, the patient
will be tested to see if their cancer is in remission. The patient and their doctor will decide if additional treatment is needed but this will not include any more SGN-40.

- Follow-up phase: Patients will be contacted every three (3) months by phone to ask how they are doing and to determine if they have received any further treatment for their lymphoma. If their disease remains under control, they will be asked to return to see their doctor and get additional tests approximately one year and two years after they began treatment.

These treatment phases are described in greater detail below.

Evaluation Phase (before beginning treatment):
Patients will need to have tests or procedures to find out if they can be in the study. These tests or procedures are usually considered part of standard care for DLBCL and may be done even if the patient does not join this study. If the patient has had some of the tests done recently, the tests may not need to be repeated. As part of the evaluation phase of the study, the patient can expect the following:
- Patients will be asked questions about: their medical history, including information
about other medical problems, all medications they are taking, allergies to medications, and their prior treatment for lymphoma.
- Patients will have a complete physical exam. This will include measuring thier vital signs (blood pressure, heart rate and temperature), height and weight.
- Blood samples will be taken from the patient's vein (approximately 2-3 tablespoons) and the patient will provide a urine sample.
- An electrocardiogram (ECG) will be done. This is a painless test that measures the electrical activity and health of the heart.
- Patients will have a CT (computed tomography) scan. This is a type of X-ray test to measure the size of any tumors in their body.
- Patients will have a PET (positron emission tomography) scan. This is a test to identify rapidly growing tumors that may be in the body.
- Patients may have a sample of their bone marrow taken. This will be done to determine if DLBCL is present in their bone marrow before they begin treatment.
- Patients may be required to have a small portion of their tumor removed (biopsy) to make sure that the disease being treated is DLBCL. The need for this procedure will be determined by the study doctor.
- Pregnancy test, as appropriate

Treatment phase:
If the study doctor determines the patient is eligible, they will start treatment. During the treatment phase of the study, patients will be given a standard combination of rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) once during each of the three treatment cycles, normally every 21 days. In addition, they will receive SGN-40 or placebo (study drug) for nine (9) weeks. All medications will be given through a vein.

SGN-40 or placebo will be given twice a week for the first week and then once a week for the duration of treatment. On Day 2 of each cycle the patient will be hospitalized for a 24-hour infusion of a chemotherapy drug (ifosfamide). The doctor may decide that it is necessary for the patient to be hospitalized at other times during the study.

Before some infusions, the patient will be required to have medications (known as premedications) that reduce the possibility of an infusion reaction. These medicines include an antihistamine like diphenhydramine (Benadryl) given through a vein or by mouth, a steroid like methylprednisolone or dexamethasone (Solumedrol or Decadron) given though a vein and a medicine like acetaminophen (Tylenol ) given by mouth. The study doctor can tell the patient more about these pre-medications including the risk of side effects. It is also very likely that the patient will receive medications and blood transfusions to treat low blood counts and to prevent infection during the time they are on treatment. These are considered standard care and will be given by the physician according to his or her usual practice.

During the nine (9) week treatment phase, there are 17 days that the patient is scheduled to receive treatment. There may be additional visits to the doctor if complications arise or treatments need to be delayed. At each visit, the patient can expect to have some or all of the following tests and procedures:
- Patients will receive one or more intravenous infusion of medication (rituximab, ifosfamide, carboplatin, etoposide, and SGN-40 or placebo) with appropriate premedications.
- Vital signs will be taken before, during and after an infusion.
- Patients will be asked questions about how they are feeling, their activity level, general well-being and information about any medications they are taking.
- Patients may have a physical examination.
- Blood will be collected from their vein (between 2-8 tablespoons) for routine safety tests and to determine how long SGN-40 and rituximab stay in their body.

Patients must not receive any other treatments for cancer while they are on this study.

Evaluations at the completion of study therapy:
Whether completing all (nine) 9 weeks of treatment or stopping study treatment early, the patient should expect to have the following tests and procedures done approximately ten (10) days after their last infusion:
- Patients will have repeat CT and PET scans.
- Patients will have a physical exam and will be asked questions about how they are feeling, their activity level and general well-being, and information about any
medications they are taking
- Blood will be collected from their vein (approximately 2-8 tablespoons).
- An electrocardiogram (ECG) will be repeated.
- A pregnancy test will be done if patient is a woman of childbearing potential.
- A urine sample will be collected.
- A bone marrow sample will be obtained if DLBCL was present in the bone marrow prior to starting treatment.

Follow-up phase:
After completing the treatment phase, the patient and their doctor will determine if additional treatment is necessary for the patient's disease. This may include an intensive treatment called stem cell transplantation. Regardless of their subsequent treatment, the patient will be included in the follow-up portion of this study which will help determine if there are any longlasting side effects of the treatment and how long the DLBCL remains under control (in remission). During this time period the patient should expect the following:
- Patients will be contacted by telephone every three (3) months. They will be asked how they are feeling and whether there has been any sign of their lymphoma, including need for additional treatment.
- If their disease remains under control, the patient will be asked to return to the clinic 1 year and 2 years after they started the study to have CT and PET scans and a
physical exam. In addition, blood samples will be taken from the patient's vein (2-8 tablespoons). Patients may have a bone marrow sample taken if there was disease in
their bone marrow at the start of the study.

How long will the Study run?

Patients will be in the study for a minimum of three (3) months (evaluation and treatment phases) and possibly as long as 42 months to complete the follow-up phase.

Sponsor(s): Seattle Genetics

Study Activation/Registration Date: 01/10/2008

IRB Review and Approval Date: 01/10/2008

Study Type: 09/19/2007

Projected Accrual: The plan is to have up to 224 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: Stephen M. Ansell, 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?

• Rochester, MN

Last updated: 05/12/2008