Clinical trial NCT00940342: Rituximab Plus Sargramostim (GM-CSF) In Patients With Chronic Lymphocytic Leukemia
Official title: Rituximab In Combination With Sargramostim (GM-CSF) In Patients With Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: Chronic Lymphocytic Leukemia
Rituximab
Leukemia
Sargramostim
GM-CSF
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2009-07-16
Enrollment: 130
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if giving granulocyte-macrophage colony-stimulating factor (GM-CSF) together with rituximab can improve the ability of rituximab to shrink or slow the growth of Chronic Lymphocytic Leukemia (CLL). The safety of this combination treatment will also be studied.

Detailed description: GM-CSF is a drug designed to stimulate the immune system. It will increase the number of a certain type of blood cell called neutrophils and macrophages.

Rituximab is a drug designed to bind to a protein, called cluster of differentiation antigen 20 (CD20), that is on the surface of the leukemia cells, allowing the leukemia cells to be destroyed by the immune system.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam, including routine blood tests (about 2 tablespoons). A bone marrow aspirate will be collected. 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a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Imaging studies (such as a chest x-ray or CT scans) may be performed. Women who are able to have children must have a negative blood pregnancy test.

If you are found to be eligible to take part in this study, you will receive GM-CSF as an injection under the skin, three times a week for eight weeks. You will receive rituximab by vein, once a week for four weeks. Usually, the first dose of rituximab requires several hours to complete. Later doses should usually be shorter, but may vary according to individual tolerance. Acetaminophen (Tylenol), diphenhydramine hydrochloride (Benadryl), and steroids (hydrocortisone or similar) will be given before rituximab to decrease the risk of side effects. If side effects do occur during the infusion, you will need to stay at the hospital and be observed until the side effects have gone away. Other than that, treatment will be given on an outpatient basis.

During treatment you will have routine blood tests (about 1 tablespoon) once a week. The treatment will take about 8 weeks to be completed. You will be taken off study if your disease gets worse or if the side effects become too severe.

After treatment is over, you will have a complete physical exam, including routine blood tests (about 2 tablespoons). A bone marrow sample will be taken. Imaging studies (such as a chest x-ray or CT scans) may be repeated to evaluate the effect of the treatment. If this treatment has worked for you, your doctor may advise you to receive it again for a second time.

You will then return for post-treatment evaluation every 6 months for 1 year and then once a year for 3 years or until you start a new treatment.

This is an investigational study. GM-CSF and rituximab have been approved by the FDA for clinical use. Their use together in this study, however, is experimental. Up to 130 patients may take part in this study. All patients will be enrolled at M.D. Anderson Cancer Center.

Eligibility criteria: Inclusion Criteria:

1. Group 1. Diagnosis of previously treated B-CLL Rai III-IV or earlier stage disease with evidence of "active disease" as defined by the NCI-sponsored working group 1) weight loss of \>10% in prior 6 months, 2) extreme fatigue, 3) fever or night sweats without evidence of infection, 4) worsening anemia or thrombocytopenia, 5) progressive lymphocytosis with a rapid lymphocyte doubling time, 6) marked hypogammaglobulinemia or paraproteinemia, 7) lymphadenopathy \>5 cm in diameter.
2. Group 2. Diagnosis of previously untreated B-CLL with Rai stage 0-II disease but high risk for progression based on B2-microglobulin \>3.0 mg/mL, or with symptoms or significant fatigue.
3. Group 3. Patients age 70 years of age and older with previously untreated B-CLL and Rai stage III-IV or earlier stage disease with indication for treatment who refused chemotherapy.
4. Age 15 years or above.
5. Adequate renal and hepatic functions (creatinine \<2.5 mg/dL, bilirubin \<2 mg/dL). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes are eligible, as are patients with elevated bilirubin and history consistent with Gilbert's disease.
6. Performance status \<3 (Zubrod Scale).
7. No active viral hepatitis

Exclusion Criteria:

1) None.

Primary outcomes:
measure: Overall Response Rate
timeFrame: Blood tests once a week during 8 weeks of treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Alessandra Ferrajoli, MD
role: PRINCIPAL_INVESTIGATOR
References: