Leukemia
Conditions
Keywords
Chronic Lymphocytic Leukemia, Rituximab, Leukemia, Sargramostim, GM-CSF
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a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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.
Interventions
250 mcg injection under the skin, three times a week for eight weeks.
DRUGRituximab
375 mg/m\^2 administered intravenously once weekly for four weeks
Sponsors
Bayer
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Blood tests once a week during 8 weeks of treatment. | 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%. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: October 2004 through January 2007. Of the 130 participants recruited, 119 participants were recruited at The University of Texas (UT) MD Anderson Cancer Center, 6 at The University of California San Diego, and 5 participants were recruited at Dana Farber Cancer Institute.
Participants by arm
| Arm | Count |
|---|---|
| Treated and Relapsed - Group 1 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.
GM-CSF (Sargramostim): 250 mcg injection under the skin, three times a week for eight weeks.
Rituximab: 375 mg/m\^2 administered intravenously once weekly for four weeks | 50 |
| Untreated and High-Risk for Progression - Group 2 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.
GM-CSF (Sargramostim): 250 mcg injection under the skin, three times a week for eight weeks.
Rituximab: 375 mg/m\^2 administered intravenously once weekly for four weeks | 40 |
| 70 Years of Age and Refused Chemo - Group 3 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.
GM-CSF (Sargramostim): 250 mcg injection under the skin, three times a week for eight weeks.
Rituximab: 375 mg/m\^2 administered intravenously once weekly for four weeks | 40 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Untreated and High-Risk for Progression - Group 2 | 70 Years of Age and Refused Chemo - Group 3 | Total | Treated and Relapsed - Group 1 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 40 Participants | 74 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 0 Participants | 56 Participants | 20 Participants |
| Age, Continuous | 56.5 years | 73 years | 69 years | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 36 Participants | 123 Participants | 49 Participants |
| Region of Enrollment United States | 40 participants | 40 participants | 130 participants | 50 participants |
| Sex: Female, Male Female | 19 Participants | 14 Participants | 49 Participants | 16 Participants |
| Sex: Female, Male Male | 21 Participants | 26 Participants | 81 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 50 | 0 / 40 | 1 / 40 |
| other Total, other adverse events | 21 / 50 | 16 / 40 | 15 / 40 |
| serious Total, serious adverse events | 5 / 50 | 3 / 40 | 4 / 40 |
Outcome results
Primary
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%.
Time frame: Blood tests once a week during 8 weeks of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treated and Relapsed - Group 1 | Overall Response Rate | 23 Participants |
| Untreated and High-Risk for Progression - Group 2 | Overall Response Rate | 31 Participants |
| 70 Years of Age and Refused Chemo - Group 3 | Overall Response Rate | 23 Participants |