Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	Other	2006-1092 NCT00539682

Trial Description

Summary

Primary Objective:

• To determine the maximum tolerated dose (MTD) of SAR3419 according to the dose limiting toxicities (DLTs) observed when administered as single agent every 3 weeks in patients with relapsed or refractory B-cell NHL.

Secondary Objectives:

• To characterize the global safety profile.

• To evaluate the pharmacokinetic (PK) profile of SAR3419 in the proposed dosing schedule.

• To assess the potential immunogenicity of SAR3419.

• To assess preliminary evidence of anti-lymphoma activity in patients with evaluable disease.

Further Study Information

The Study Drug:

SAR3419 is designed to stop tumor growth and kill cancer cells by binding to CD19 molecules on the surface of lymphoma cells.

Screening Tests:

Before you can start treatment on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests will be performed:

• Your complete medical history will be recorded

• You will have a physical exam including measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate).

• Blood (about 3 tablespoons) will be drawn for routine tests.

• Urine will be collected for routine tests.

• Women who are able to have children must have a negative blood (one teaspoon) pregnancy test.

• You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

• You will have a bone marrow aspirate. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will have x-rays, positron emission tomography (PET) scans, and computerized tomography (CT) scans of the neck, chest, abdomen, and pelvis, to check the status of the disease.

Study Drug Dose Level:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of SAR3419, based on when you joined this study. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of SAR3419 is found.

Study Drug Administration:

You will receive SAR3419 through a needle in your vein on Day 1 of each study cycle. Each "study cycle" is 21 days. The SAR3419 infusions will range from 30 minutes to 4 hours, depending on the dose level you will receive. About 30 minutes before starting the infusion, you will receive the following medications to prevent allergic reactions: diphenhydramine and acetaminophen. During and after infusion of SAR3419, your doctor will watch you for any side effects. Your doctor may add medications to help treat side effects and will discuss any medications and their risks and benefits with you.

Study Visits:

You will be asked to visit the clinic at different times during the study. The following tests and procedures will be performed:

• You will have a physical exam on Day 1 of all cycles.

• You will have 3 ECGs on Day 1 of all cycles.

• You will be asked about any side effects you have experienced and any treatments you have had since your last visit on Day 1 of all cycles.

• Blood (about 3 tablespoons) will be drawn twice a week during Cycle 1 and at least weekly during all other cycles, for routine tests.

• Blood (about 5 tablespoons) will be drawn on Days 1, 2, 3, 5, 15, and 21 for PK testing during Cycle 1.

• For Cycles 2 and after, blood (about 4 ½ tablespoons) will be drawn on Days 1 and 21 (plus or minus 3 days) for routine tests.

• You will have a CT scan and PET scan performed to check the status of the disease, every 2 cycles.

You may be asked to return to the clinic between routine study visits, based on the results of your blood tests. Your study doctor or the sponsor may decide that another blood sample should be taken before the next study visit.

Length of Study:

If the disease does not get worse and no intolerable side effects occur, you may receive up to 6 cycles of SAR3419 over 5 months. You will be taken off-study if the disease gets worse or intolerable side effects occur.

Follow-up Visit:

About 6 weeks after your last dose of SAR3419, your will be asked to visit the clinic. The following tests and procedures will be performed:

• You will have a physical exam.

• You will have 3 ECG's.

• Blood (about 3 tablespoons) will be drawn for routine tests.

• Urine will be collected for routine tests.

• You will have a blood (about 1 teaspoon) pregnancy test.

This is an investigational study. SAR3419 is not FDA approved and it is not commercially available. All drugs to help allergic prevent reaction are FDA approved and commercially available. Up to 40 patients will take part in this multicenter study. Up to 40 will be enrolled at M. D. Anderson.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed CD19-positive non Hodgkin's lymphoma.

• Relapsed or refractory after standard treatments and with no curative option with conventional therapy.

• Bidimensionally measurable disease.

• No evidence of cerebral or meningeal involvement by lymphoma.

• Age >/= 18 years.

• ECOG performance status 0 to 2.

• Life expectancy of at least 3 months.

• Signed informed consent form prior to enrollment.

Exclusion Criteria:

• Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included).

• Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study.

• Previous radioimmunotherapy within 12 weeks.

• Patient with active infections or HIV infection.

• Known active viral hepatitis.

• Known intolerance to infused protein products or maytansinoids (an anti-tumor medication that is a derivative of a natural plant).

• Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study.

• Poor bone marrow reserve as defined by absolute neutrophil count < 1.5 x 10^9/L or platelets < 100 x 10^9/L.

• Baseline QTc interval > 500 msec (determined as the median of three EKGs done within a 30-min period) (Grade >/= 3 NCI-CTC v3.0)

• Poor organ function as defined by one of the following: a.) Total bilirubin > 1.5 x ULN (>3 x ULN for patients with liver involvement); b.) AST, ALT > 2.5 x ULN (> 5 x ULN for patients with liver involvement); c.) Serum creatinine > 2 x ULN and/or creatinine clearance < 60 mL/min

• Pregnant or breast-feeding women (sexually active females of childbearing potential must have a negative serum or urine pregnancy test).

• Refused to use effective birth control methods if applicable. Women that can have children must use a medically acceptable method of birth control while participating in the study (birth control pill, intrauterine device or injection of Depo-Provera) and for at least 30 days after the last dose of study medication.

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Anas Younes

Principal Investigator

Anas Younes, MD

Ph: 713-792-2860

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
Ohio
	Cleveland
	Cleveland Clinic Taussig Cancer Center
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Anas Younes	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00539682
Information obtained from ClinicalTrials.gov on March 18, 2009