IRB Number:

07-007337

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

Patients are being asked to take part in this research study because they have relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The purpose of this study is to test how well an investigational drug called SGN-40 works in combination with gemcitabine and rituximab, two commonly used drugs for certain types of cancer. The study doctors hope to find out what a safe dose is when these three study drugs are combined, what the side effects are, and whether or not they are an effective combination in treating relapsed or refractory DLBCL. More than 100 people with cancer have received SGN-40 in earlier research studies. These previous research studies were used to evaluate the safety of different doses and schedules of SGN-40 when given on its own.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
-Patients must have relapsed, refractory, or progressive disease following intensive salvage therapy, OR must have relapsed, refractory, or progressive disease following initial therapy and be medically unfit to receive intensive therapy [defined as combination chemotherapy +/- autologous SCT (stem cell transplant)].

*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 SGN-40, rituximab, and gemcitabine for up to eight cycles of treatment. Each cycle is four weeks long (32 weeks). Patients will be assessed every two months while they are on the study treatment to see if the combination of the three drugs is controlling their cancer.
- Follow-up phase: If a patient's disease remains under control, the patient will be asked to return to the clinic to visit the study doctor and complete additional tests every six weeks.

Evaluation Phase (before patients begin 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 completed even if a patient does not join this study. If patients have had some of them done recently, they may not need to be repeated.

As part of the evaluation phase of the study, patients can expect the following:
- Questions about their medical history and past treatments for DLBCL, including information about other medical problems, allergies to medications, blood or platelets (cells that help the blood to clot), transfusions and past and/or present use of growth factors (medications that increase patients white or red blood cells) and their prior treatment for lymphoma.
- A complete physical exam. This will include having vital signs (blood pressure, heart rate, temperature and breathing rate), height, and weight measured.
- Questions about any signs or symptoms that have developed, and the names, doses, and frequency of all medications taken by the patient will be recorded.
- A blood sample to check blood counts, chemistries, kidneys, liver, thyroid, the ability of a patient's blood to clot, and general inflammatory tests.
- A urine sample for routine tests.
- An electrocardiogram (ECG) will be done. This is a painless test that measures the electrical activity and health of the heart.
- A computed tomography (CT) scan will be performed. This is a type of X-ray test to measure the size of any tumors in a patient's body.
- A positron emission tomography (PET) scan will be performed. This is a test to identify tumors that may be growing in a patient's body.
- A pregnancy test if the patient is able to become pregnant and follow birth control guidelines.
- 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 doctor.

Treatment Phase:
Once it is determined that patients are eligible for the study and they agree to continue, patients will begin SGN-40 therapy as described below:

- SGN-40 will be given as an intravenous (into a vein [IV]) infusion.
- Treatment of SGN-40 will be divided into cycles of 4-week duration. Patients may be eligible to receive up to eight cycles of treatment.
- During the first cycle only, Patients will receive two doses of SGN-40 in the first week (Days 1 and 4) which means that they will receive five infusions in Cycle 1.
During all other cycles, patients will receive SGN-40 on a weekly basis (Days 1, 8, and 15), which means that they will receive three infusions per cycle for Cycles 2-8.
- Patients may be eligible to receive up to 26 infusions of SGN-40 through all cycles of treatment.

At the same time as SGN-40, patients will begin rituximab therapy as described below:

- Treatment will be divided into cycles of 4-week duration. Patients may be eligible to receive up to eight cycles of treatment. Rituximab will be given as an IV infusion four times for the first four weeks of treatment during Cycle 1 (Days 1, 8, 15, and 22). It will then be given as an IV infusion only once per cycle for Cycles 2-8 (Day 1 only).
- Patients may be eligible to receive up to 11 infusions of rituximab through all cycles of treatment.

At the same time patients begin SGN-40 and rituximab, they will begin gemcitabine therapy as described below:

- Treatment will be divided into cycles of 4-week duration. Patients may be eligible to receive up to eight cycles of treatment. Gemcitabine will be given as an IV infusion
given three times every four weeks of treatment (Days 1, 8, and 15).
- Patients may be eligible to receive up to 24 infusions of gemcitabine through all cycles of treatment.

To decrease the risk of side effects of SGN-40 and rituximab, before some infusions, patients will be required to have medications (known as pre-medications) that reduce the possibility of an infusion reaction. These medicines include an antihistamine like diphenhydramine (Benadryl) given through a vein or as a tablet and taken by mouth, and
a medicine like acetaminophen (Tylenol) given by mouth. Before some infusions patients may also be required to receive a steroid like methylprednisolone or dexamethasone
(Solumedrol or Decadron) given through a vein or by mouth. The study doctor can explain more about these pre-medications including the risk of side effects. It is also very likely that patients 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 treatment, additional testing will be done to evaluate side effects and to determine patient's response to therapy. The tests and schedule will be:

- A complete physical examination performed once every cycle.
- At every visit that patients have with their study doctor and the research study staff, patients will be asked about any signs or symptoms that have developed, and the
names, doses, and frequency of all medications taken by patients will be recorded.
- Patient's blood pressure, temperature, and heart rate will be checked during each infusion.
- Blood samples will be collected on each day patients receive an infusion to determine how long SGN-40 and rituximab stay in their body, how the medications affect their blood cells, liver, kidneys, and chemistries, and if their body has made antibodies against the medications.
- A PET/CT scan will be performed to determine how patient's cancer has reacted to the study therapy.
- A small sample of bone marrow and fluid may be taken if a patient's disease was known to be in the patient's bone marrow at the start of the study.

Within three weeks after the last dose of SGN-40, whether or not patients stop the study early, additional testing will be completed to evaluate side effects and to determine their response to therapy. The tests and schedule will be:

- A complete physical examination.
- Blood samples will be collected to check their blood counts, chemistries, and kidney and liver function. Also, their blood will be checked to determine how long SGN-40 and rituximab stay in their body and if thier body has made antibodies against the medications.
- A pregnancy test if a patient is able to become pregnant.
- Questions about any signs or symptoms that have developed, and the names, doses, and frequency of all medications taken by patients will be recorded.
- An ECG (electrocardiogram) will be performed.
- A small sample of bone marrow and fluid may be taken if a patient's disease was known to be in the patient's bone marrow at the start of the study.

The total amount of blood collected for tests on a treatment day will be approximately 5 tubes or about 7 teaspoons. This is a normal amount of blood to be taken during a clinical trial and is not a dangerous amount to be taken.

Follow-up Phase (after stopping treatment):

Beginning every 6 weeks after completing the treatment phase, if a patient's disease remains under control, the patient will be asked to continue visits to the research clinic. The research study staff will provide follow-up information, evaluate the status of the patient's cancer, ask about any additional therapy that the patient may have received after SGN-40, rituximab and gemcitabine was stopped, and evaluate any side effects from the study therapy. The following tests will also be performed:

- A blood sample to check the patient's blood counts, chemistries, and kidney and liver function.
- A CT scan to evaluate the patient's tumor.

How long will the Study run?

Patients will be in the study for up to 10 months on active treatment. After active treatment is complete, follow-up will continue every six weeks until their disease shows signs of worsening. When patients are no longer receiving study treatment, the research staff will ask patients to remain on the research study for up to one year after the study is completed, or until patients request to stop. Patients will be asked to visit the clinic every six weeks so research staff can conduct follow-up procedures and collect follow-up information about patients' health.

Sponsor(s): Seattle Genetics, Inc.

Study Activation/Registration Date: 05/23/2008

IRB Review and Approval Date: 03/12/2008

Study Type: Treatment

Projected Accrual: The plan is to enroll up to 32 patients to 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: Donald W. Northfelt, 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: 07/09/2008