IRB Number:

07-008250

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 a type of cancer called multiple myeloma that has reoccurred after initially responding to treatment or they have failed to respond to a previous treatment. The purpose of this study is to test the safety of SGN-40 at different dose levels when combined with a drug called bortezomib (Velcade). The research staff want to find out what effects, good and/or bad, it has on patients and their multiple myeloma. It will also determine the highest tolerated dose of SGN-40 that may be used in other studies.




The use of SGN-40 in this research study is experimental which means that it is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma. Bortezomib is approved by the FDA for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with multiple myeloma that has reoccurred after initially responding to treatment or failed to respond to a previous treatment
-Patients can be bortezomib-naïve (never received bortezomib) or have previously received bortezomib at any time in the past.

*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:
Patients will receive SGN-40 in combination with bortezomib. Since the research staff is looking for the highest dose of SGN-40 that can be given to people in combination with bortezomib safely, not everyone who participates in this study will receive the same
amount of SGN-40, but patients and their study doctors will know which dosage amount is being received.

The study consists of the following parts:
1. A 28-day screening period
2. A treatment period lasting up to 24 weeks
3. A 6-week follow-up period
4. Additional follow-up for approximately one year following the patient's first study treatment or until the disease progresses.

Screening
Before beginning the study patients will need to have the following exams, tests, or procedures to find out if they can participate in the study. Some of these exams, tests or
procedures may be part of patient's regular medical care and may be done even if they do not join the study. If patients have had some of them recently, they may not need to be repeated. This will be up to the study doctors.

- Assessment of patient's performance status (their ability to perform daily activities)
- Recording of patient's demographic information (age, sex, race/ethnicity as reported by the patients)
- Recording of patient's general medical, surgical, and cancer history, including medications that they are taking or may have taken in the 28 days prior to the first day of study treatment (Day 1 of Cycle 1)
- Physical examination, including a neurological assessment (review of patient's vision, strength, coordination, reflexes, and sensation) and measurement of their blood pressure, heart rate, temperature, height and weight
- An electrocardiogram (ECG). An ECG measures the electrical activity of the heart. An ECG requires temporary placement of electrical sensors on patient's chests near the heart, on their wrists, and on their ankles.
- A chest x-ray
- Collection of blood samples for laboratory tests (approximately 2 to 3 tablespoons) to evaluate patient's blood counts, their clotting ability, and to test their body organ functions
- Collection of blood samples for laboratory tests (approximately 2 to 3 tablespoons) to evaluate the patient's disease. These tests will measure levels of different proteins in the patients' blood that may change due to treatment or due to changes in their disease case.
- Collection of a urine sample for standard laboratory tests including: pH, glucose, protein, ketones, and blood
- Collection of a urine sample over 24 hours to determine if certain proteins are present in patient's urine.
- If patients are women of childbearing potential, even if they have had a tubal ligation, they must use reliable contraception during the study and for one year after
their last study drug dose. A serum pregnancy test will be done on a blood sample taken at the screening visit.
- Collection of samples of patient's bone marrows.
- A skeletal survey. A skeletal survey is a series of X-rays of patient's bones to determine where tumor deposits appear in their bodies.
- A computed tomography (CT) scan. A CT scan is a special test that produces an image of patient's body using a small amount of radiation. The image shows the body tissues and structure in three dimensions (3-D).

Study Treatment Phase
If the exams, tests, and procedures during the screening phase show that the patient can be in the study, and the patient chooses to take part, the patient will begin the treatment phase of the study.

Study Treatment Administration
Patients will receive SGN-40 and bortezomib for a maximum of eight cycles. A cycle is a scheduled period of time for taking cancer treatment drugs. For this study, each cycle is
21 days (or three weeks) long. The dose of SGN-40 patients receive will depend on the number of patients that have been enrolled in this study before the patient and how well they have tolerated their doses of the drug. The doctor will tell the patient what dose of SGN-40 the patient will receive and how this compares with the doses other participants have received. At this time, the research staff does not know which dose is likely to be most effective. Once a dose of SGN-40 that can be given without causing serious or unmanageable side effects has been determined, up to 20 more people may be enrolled at this dose.

All patients will start at the same dose of bortezomib at 1.3 mg/m2. SGN-40 will be administered by intravenous (IV) infusion (infused into the patient's vein). During the first cycle only, patients will receive four infusions of SGN-40 (on Days 1, 4, 8 and 15) in order to gradually increase the dose. For subsequent cycles the patient will receive the same dose of SGN-40 on Days 1 and 8 of each 21-day cycle for a maximum of eight cycles.

Patients will be treated with bortezomib, given as a three to five-second injection into their veins on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles.
On days when both SGN-40 and bortezomib are given on the same day, the bortezomib injection will be given first followed by the SGN-40 infusion approximately 15 to 30 minutes later.

Before and after each dose of SGN-40, patients will be given medications to reduce the chances of the patients having an allergic-type reaction (for example, fever or itching) to the study drug. These medications will be given at the discretion of the study doctor and may include acetaminophen (e.g. Tylenol), which is given by mouth, diphenhydramine (e.g., Benadryl), which is given by mouth or by vein, methylprednisone, which is given by vein and/or prednisone, which is given by mouth.

The first infusion of SGN-40 will be given at a slow rate for the first hour. If the patient does not have any side effects, the speed of infusion may be increased. The first infusion may last longer than the rest of the infusions and may take as long as three to five hours. It is possible it may take longer, depending on how well the patient tolerates the treatment.

There will be no dose reduction allowed for SGN-40. If the patient experiences a reaction that could be related to study drug infusion, the study doctor may stop the infusion, treat the patient's symptoms, and then restart the infusion, or withdraw the patient from the study. Patients will be carefully monitored for any side effects from the infusion. Dose reduction may be allowed for bortezomib based on the type and severity of any side effects the patient experiences.

Study Visits
During the treatment period of the study patients will be asked to return to the clinic regularly to receive study treatment and for the following tests and procedures. Many of these tests and procedures are also part of regular medical care; however, they may be done more often for this study.

- The study doctor will ask the patient about the following: Any health problems the patient has had since the last visit and any medications the patient is taking.
- Patient will have a physical exam.
- Patient will have their blood pressure, heart rate and temperature taken.
- Patient's performance status will be evaluated.
- Patient's weight will be taken.
- An ECG will be performed.
- Routine blood tests will be performed (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- Additional blood tests will be performed to evaluate the patient's disease and to measure how the body processes the study drugs (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- A bone marrow aspirate and biopsy may be performed only if the patient has no other signs of myeloma on the other tests and if there were tumor cells found in the patient's
bone marrow at screening.
- A skeletal survey may be performed if the patient's symptoms or disease becomes worse.
- A CT scan may be performed to assess changes in the patient's disease.
- A urine test may be performed (if necessary, a kit will be given to the patient to collect a urine sample over a 24-hour period).

Early Termination Visit
If the patient chooses to withdraw from this research study before Cycle 2, Day 15 of the study or participation is ended by the doctor or Genentech for any reason, the patient will be asked to complete a termination study visit within 14 days. At this visit, the patient will have the following tests and procedures. Some tests and procedures may not be necessary if the patient has had them recently. The study doctor will determine which tests and procedures the patient needs:

- The study doctor will ask the patient about the following: any health problems the patient has had since the last visit and any medications they are taking.
- Patients will have a physical exam.
- Patients will have their blood pressure, heart rate and temperature taken.
- Patients performance status will be evaluated.
- An ECG will be performed.
- Routine blood tests will be performed (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- Additional blood tests will be performed to evaluate the patient's disease and to measure how their body processes the study drugs (approximately 2 to 3 tablespoons of
blood will be collected for these tests).
- Collection of a urine sample for laboratory tests including: pH, glucose, protein, ketones and blood.
- A bone marrow aspirate and biopsy may be performed only if the patient has no other signs of multiple myeloma on the other tests and if there were tumor cells found in the
bone marrow at screening.
- A skeletal survey may be performed if the patient's symptoms or disease becomes worse.
- A CT scan may be performed to assess changes in the patient's disease.
- A urine test may be performed (if necessary, a kit will be given to the patient to collect a urine sample over a 24-hour period).

Follow-Up Phase
After the patient has stopped receiving study treatment, the following procedures will be performed every two weeks for six weeks. Many of these tests and procedures are also
part of patient's regular medical care; however, they may be done more often for this study:

- The study doctor will ask the patient about the following: Any health problems the patient has had since the last visit and any medications the patient is taking.
- The patient's performance status will be evaluated (at the six week visit only).
- Patients will have a physical exam (at the six week visit only).
- An ECG will be performed (at the six week visit only).
- Routine blood tests will be performed (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- Additional blood tests will be performed to evaluate the patient's disease and to measure how their body processes the study drugs (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- A bone marrow aspirate and biopsy may be performed only if the patient has no other signs of myeloma on the other tests and if there were tumor cells found in their bone marrow at screening.
- A CT scan may be performed to assess changes in the patient's disease.
- A skeletal survey may be performed if the patient's symptoms or disease becomes worse or at least once per year.
- A urine test may be performed (if necessary a kit will be given to the patient to collect a urine sample over a 24-hour period).

Additional Follow-Up
After the six-week follow-up phase of the study, patients will be asked to continue coming to the clinic every six weeks until their cancer progresses, they start a new treatment for their multiple myeloma, or until they complete at least 52 weeks on the study from Treatment Day 1. The following assessments will be performed:

- The study doctor will ask the patient about the following: Any health problems the patient has had since the last visit.
- Blood tests will be performed to evaluate the patient's disease and to measure how the body processes the study drugs (approximately 2 to 3 tablespoons of blood will be collected for these tests).
- A bone marrow aspirate and biopsy may be performed only if the patient has no other.
signs of multiple myeloma on the other tests and if there were tumor cells found in their bone marrow at screening.
- A CT scan may be performed to assess changes in the patient's disease.
- A skeletal survey may be performed if the patient's symptoms or disease becomes worse or at least once per year.
- A urine test may be performed (if necessary a kit will be given to the patient to collect a urine sample over a 24-hour period).

How long will the Study run?

Patients will be in the study for about 1 year from screening to the last follow-up visit, unless they withdraw or are discontinued from the study.

Sponsor(s): Genentech, Inc.

Study Activation/Registration Date: 05/14/2008

IRB Review and Approval Date: 04/16/2008

Study Type: Dosing/Treatment

Projected Accrual: The plan is to enroll up to 38 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: Joseph Mikhael, 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