Rituximab Plus Sargramostim (GM-CSF) In Patients With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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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
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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a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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.

Official Title
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Rituximab In Combination With Sargramostim (GM-CSF) In Patients With Chronic Lymphocytic Leukemia (CLL)

Conditions
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Leukemia

Intervention / Treatment
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* Drug: GM-CSF (Sargramostim)
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. 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. Age 15 years or above. 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. Performance status <3 (Zubrod Scale). No active viral hepatitis Exclusion Criteria: 1) None.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated and Relapsed - Group 1<br>Participants receive one (1) course of therapy. One course of therapy consists of four (4) doses of Rituximab 375 mg/m2, administered once weekly by vein for 4 weeks along with GM-CSF 250 mcg subcutaneously three times weekly for 8 weeks. | Drug: GM-CSF (Sargramostim)<br>* 250 mcg injection under the skin, three times a week for eight weeks.<br>* Other names: Leukine;Drug: Rituximab<br>* 375 mg/m^2 administered intravenously once weekly for four weeks<br>* Other names: Rituxan;|
| Experimental: Treated and High-Risk for Progression - Group 2<br>Participants receive one (1) course of therapy. One course of therapy consists of four (4) doses of Rituximab 375 mg/m2, administered once weekly by vein for 4 weeks along with GM-CSF 250 mcg subcutaneously three times weekly for 8 weeks. | Drug: GM-CSF (Sargramostim)<br>* 250 mcg injection under the skin, three times a week for eight weeks.<br>* Other names: Leukine;Drug: Rituximab<br>* 375 mg/m^2 administered intravenously once weekly for four weeks<br>* Other names: Rituxan;|
| Experimental: 70 Years of Age and Refused Chemo - Group 3<br>Participants receive one (1) course of therapy. One course of therapy consists of four (4) doses of Rituximab 375 mg/m2, administered once weekly by vein for 4 weeks along with GM-CSF 250 mcg subcutaneously three times weekly for 8 weeks. | Drug: GM-CSF (Sargramostim)<br>* 250 mcg injection under the skin, three times a week for eight weeks.<br>* Other names: Leukine;Drug: Rituximab<br>* 375 mg/m^2 administered intravenously once weekly for four weeks<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate - Complete Response (CR) + Partial Response (PR). CR is the absence of Lymphocyte infiltrates on biopsy, <30% Lymphocytes on Bone Marrow Aspirate, Lymphocytes < 4,000ul , Hemoglobin >11.0 g/dl , Platelets >1000,000/ul, Polymorphonuclear neutrophils (PMN) >1,500/ul, Liver/Spleen not palpable, Nodes none. PR is <30% Lymphocytes with residual disease on biopsy for nodular PR, Lymphocytes >50% decrease, Hemoglobin (un-transfused) > 11.0 g/dl or >50% improvement from baseline, Platelets > 100,000/ul or 50% improvement from baseline, PMN >1,500 ul or 50% improvement from baseline, Liver/Spleen >/= 50% decrease, Nodes >/= 50%. | Blood tests once a week during 8 weeks of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia, Rituximab, Leukemia, Sargramostim, GM-CSF