Phase II Trial of Rituximab Plus Sargramostim for Newly Diagnosed Follicular B-Cell Lymphoma in Adults

Condition(s) targeted: Lymphoma; Follicular B-Cell Lymphoma

Intervention: Rituximab (Rituxan) (Drug); Sargramostim (Leukine) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Peter McLaughlin, MD, Principal Investigator, Affiliation: U.T. M.D. Anderson Cancer Center

Overall contact:
Peter McLaughlin, MD, Phone: 713-792-2860

Primary:

To determine the safety and efficacy of repeat doses of rituximab plus sargramostim for the treatment of adults with newly diagnosed follicular B-cell lymphoma. The primary endpoint is to assess complete response (CR) at 12 weeks.

Secondary:

1. Overall response (OR) rate

2. Progression-free survival (PFS) at 3 years

3. Adverse event profile

4. Survival

5. To determine the effect of Fc gamma receptor polymorphism on response rate and time to progression of lymphoma patients

Correlative Study Objective:

To determine the effect of Fc gamma receptor polymorphism on response rate and time to progression of lymphoma patients treated by combination therapy with rituximab and sargramostim.

Official title: Single-Arm, Open-Label, Phase II Trial of Rituximab Plus Sargramostim for the Treatment of Newly Diagnosed Follicular B-Cell Lymphoma in Adults

Study design: Interventional, Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Detailed description: Rituximab is designed to attach to lymphoma cells, which may cause them to die. Sargramostim is designed to increase the number and function of white blood cells. White blood cells are responsible for fighting infections and activating an immune response. Rituximab and sargramostim may be more effective in combination than either drug is by itself.

Before you can start treatment on this study, you will have "screening tests. ” These tests will help the doctor decide if you are eligible to take part in this study. Blood (about 2-4 teaspoons) will be drawn for routine tests. You will have a physical exam, including measurement of your vital signs, (blood pressure, heart rate, temperature, and breathing rate) height, and weight. You will have a bone marrow biopsy. To collect a bone marrow biopsy, an area of your right and/or left hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

A lymph node biopsy will also be performed. A lymph node biopsy is a procedure in which all or part of a lymph node is removed and tested to determine if there is cancer within the node. The procedure may be done by surgery or by needle (called a fine needle aspiration or FNA). The decision to use surgery or FNA will be based on the location of the node. A open lymph node biopsy is the surgical procedure. The surgeon makes a small cut and removes either the entire lymph node or a slice of tissue that is then sent to the laboratory for testing. In a FNA biopsy, a needle is inserted through the skin and into the lymph node, and a sample of tissue is drawn out of the node.

You will have an electrocardiogram (ECG - a test that measures the electrical activity of the heart). You will have a computed tomography (CT) scan or a magnetic resonance imaging (MRI) of the chest, abdomen (stomach area), and pelvis. Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy test.

If you are found to be eligible to take part in this study, you will receive rituximab through a needle in your vein 1 time a week for 4 weeks on Days 1, 8, 15, and 22. Every 4 weeks (28 days) is considered a study "cycle".

You will receive sargramostim through a needle under your skin (subcutaneous injection) 1 hour on Day 1 of Week 1 and then on Days 1, 3, and 5 of each week for 8 weeks. Blood (about 1-2 teaspoons) will be drawn at each of your rituximab treatments to check your blood cell counts. A physical exam along with measurement of your vital signs and weight may also be done at these times. At each visit, you will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

On Day 1, you will receive your first subcutaneous injection of sargramostim and then you will receive rituximab through a needle in your vein (by IV) 1 hour later. The drug will be given slowly at first to allow your body to adjust to the treatment. You will be closely monitored while you receive the drug to make sure that you tolerate the treatment well. To help make you more comfortable, you may receive extra fluids through your IV tube before you begin treatment. You may also receive drugs to help you avoid chills, fever, or allergic symptoms.

On Days 3 and 5 of Week 1, you will give yourself additional injections of sargramostim. You and/or a family member will be taught how to safely give sargramostim. You will then continue to give yourself sargramostim injections on Days 1, 3 , and 5 of each week for the next 7 weeks, for a total of 8 weeks (24 injections). You will write down when the drug is given in a drug "diary". During the 8 weeks on study, you will also be asked to report any symptoms or side effects that may occur.

After the first 4 weeks, you will only take sargramostim. You will take sargramostim at your home on Days 1, 3, and 5 of Weeks 5-8.

You will have weekly study visits while on active study treatment. At these visits, blood (about 1-2 teaspoons) will be drawn for routine tests.

At Week 4, additional blood samples (1-2 teaspoons) will be drawn for routine tests and to look at immunoglobulins. Immunoglobulins are proteins in the blood which play an essential role in the body’s immune system by attaching themselves to certain foreign substances, such as bacteria, and assist in destroying them.

At Week 8, you will have a CT scan or MRI to check the status of the disease.

If your first bone marrow biopsy was positive, you will have additional bone marrow biopsies at Weeks 4 and 8.

After you have completed the 8 weeks of treatment you will be asked to return to the clinic in 1 month (Month 3) and then every 3 months for 2 years and then every 6 months for another 1 year. At each of these visits, blood (about 1-2 teaspoons) will be drawn for routine tests. You will also have a performance status evaluation. You will be asked about any symptoms and side effects you may be experiencing. You will have a physical exam, and a CT scan or MRI. At Months 3, 6, 9,12,18, and 24 an additional 1-2 teaspoons of blood will be drawn for measurement of immunoglobulins. If you had a positive bone marrow biopsy, you will have an additional biopsy at Month 15.

You will be considered off study after your 36-month visit. You will be taken off study if the disease gets worse, intolerable side effects occur, or another illness prevents you from participating any longer.

This is an investigational study. Rituximab and sargramostim are both FDA approved and commercially available. The use of rituximab and sargramostim together in this study is investigational. Sargramostim will be provide to you free of charge during the study by the study sponsor. The cost of rituximab will be the responsibility of you and/or your insurance provider. Up to 52 patients will take part in this multicenter study. Up to 20 will be enrolled at M. D. Anderson.

Minimum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1) Patients must have histologically confirmed newly diagnosed follicular B-cell lymphoma.

2) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan.

3) Patients should not have received prior therapy of any kind for follicular B-cell lymphoma.

4) Age >/= 18 years. Because no dosing or adverse event data are currently available for the use of rituximab in combination with sargramostim in patients (males or females) <18 years of age, children are excluded from this study.

5) ECOG performance status /= 60%).

6) Patients must have normal organ and marrow function as defined below: - leukocytes >/= 3,000/microL; - absolute neutrophil count >/= 1,500/microL; - platelets >/= 100,000/microL; -total bilirubin within normal institutional limits; - AST(SGOT)/ALT(SGPT) /= 60 mL/min/1. 73 m^2 for patients with creatinine levels above institutional normal

7) Hemoglobin >/= 8. 0 gm/dL

8) The effects of rituximab and sargramostim on the developing human fetus at the recommended therapeutic doses are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

9) Ability to understand and the willingness to sign an informed consent document.

Exclusion Criteria:

1) Prior therapy of any kind for follicular B-cell lymphoma.

2) Patients may not be receiving any other investigational agents.

3) Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4) History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab or other agents used in the study.

5) Rituximab is contraindicated in patients with known anaphylaxis or IgE-mediated hypersensitivity to murine proteins. Sargramostim is contraindicated in patients with excessive leukemic myeloid blasts, with known hypersensitivity to GM-CSF or yeast-derived components of the recombinant, and for concomitant (or within 24 hours ± of) uses with chemotherapy or radiotherapy.

6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

7) Pregnant women are excluded from this study.

8) Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions.

9) Patients with evidence of active or prior infection of Hepatitis B are excluded. (Note: Persons vaccinated for Hepatitis B who have positive antibodies are not excluded).

Peter McLaughlin, MD, Phone: 713-792-2860

U.T. M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Peter McLaughlin, MD, Principal Investigator

Starting date: November 2006
Last updated: December 8, 2006