Leukemia
Conditions
Keywords
Chronic Lymphocytic Leukemia, Leukemia, Sargramostim, Pneumococcal Pneumonia, Pneumococcal Vaccine, Prevnar, GM-CSF, CLL
Brief summary
The goal of this clinical research study is to see if Leukine(R) (sargramostim) improves the effectiveness of the pneumococcal vaccine, a medicine used to prevent pneumococcal pneumonia, in patients with chronic lymphocytic leukemia (CLL).
Detailed description
Sargramostim (also commonly called granulocyte macrophage colony stimulating factor - GM-CSF) is a medication used to stimulate the bone marrow production of white blood cells before a stem cell transplant, after chemotherapy or after a bone marrow transplant. Pneumococcal vaccine is a medication used to prevent infections caused by a bacteria called Streptococcus pneumoniae. If you have not had a gammaglobulins test (a test to measure immunity against certain infectious diseases) measured within three months before the study begins, then this blood test will be done before you receive any study medications. Women who are able to have children must have a negative urine pregnancy test before starting treatment. After consenting to this study, you will be randomly assigned (as in the toss of a coin) to receive treatment with sargramostim in addition to the pneumococcal vaccine or to receive pneumococcal vaccine alone (Prevnar). * If you are randomized to vaccine plus sargramostim group, you will receive an injection of sargramostim at the same time you receive the pneumococcal vaccine. * If you are randomized to the vaccine alone group, you will receive the pneumococcal vaccine on the first day. Blood tests will be performed on the day of the pneumococcal vaccination, and 4 weeks, 12 weeks and 24 weeks after vaccination. Each of the blood tests will require about 4 teaspoons of blood. These blood tests will measure your immunity to pneumococcal infection. If after 6 months of your first vaccination your body is not able to show immunity to pneumococcal infection, you will receive a second dose either pneumococcal vaccine plus sargramostim or pneumococcal vaccine alone. Your immunity will be checked again at 4 weeks, 12 weeks, and 24 weeks after this second dose. Only 4 teaspoon of blood will be required for the tests. You may be removed from the study if you have a severe allergic reaction to the sargramostim and/or pneumococcal vaccine. The total maximum time you will be on this is study is 24 months. This is an investigational study. Both of the medications used in this study are approved by the FDA. Up to 50 patients may be treated on this study. All will be enrolled at M.D. Anderson.
Interventions
Starting with 3 doses of 250 micrograms subcutaneously, either pre or post vaccine. For pre vaccine, GM-CSF on days -7 (+ 1 day) and -3 (+ 1 day), in the week prior to vaccination for pre-vaccination immune priming; 3rd dose on the day of vaccination (day 0); and for post-vaccine GM-CSF given simultaneously on day of vaccination (day 0) and 2 more doses Day +3 and Day +7 after pneumococcal vaccine.
BIOLOGICALPneumococcal Vaccine
Subcutaneously on Day 0
Sponsors
Bayer
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1\) Patients in complete / partial remission or those with active Chronic lymphocytic leukemia (CLL) with Rai stage 0 to 4.
Exclusion criteria
1. Patients will not be entered while neutropenic (PMNs \< 500 cells/mm3) or having received Rituximab within 6 months. 2. Patients will not be entered while febrile (Temperature \> 38 degrees C) within 1 week. 3. Active infection. 4. Patients with known Human immunodeficiency virus (HIV) infection. 5. Known history of allergy to Granulocyte/ macrophage colony stimulating factor (GM-CSF) or pneumococcal vaccine. 6. Chemotherapy other than Campath, fludarabine, cyclophosphamide, in 4 weeks. 7. Patients who have previously received pneumococcal vaccine within the preceding 12 months. 8. Absolute lymphocyte count less than 500 cells/mm3.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Baseline and at 1 month after vaccine. | Response defined as 2-fold rise in anticapsular immunoglobulin G (IgG) when prevaccination titer is compared with levels post vaccination and with a final level of \>0.5 ug/mL. Anti-pneumococcal immunoglobulin titers measured at baseline and 1 month after vaccine. Response determined by measuring serum IgG to capsular polysaccharides from 6 of the most common infecting serotypes of Streptococcus pneumoniae. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: December 9, 2004 to July 16, 2009. All participants were recruited at UT MD Anderson Cancer Center.
Pre-assignment details
Of the 39 enrolled participants, four (4) participants withdrew consent and three (3) were ineligible thus all seven (7) were excluded from the trial before assignment to Pneumococcal Vaccine and Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) related treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Pneumococcal Vaccine + GM-CSF Vaccine subcutaneously + GM-CSF (3 Doses of 250 mg subcutaneously) given either Pre Vaccine at Day -7, Day -1 and Day 0 (day of pneumococcal vaccine) or Post Vaccine given at Day 0, Day +3 and Day +7. | 25 |
| Pneumococcal Vaccine Alone First vaccine dose subcutaneously, Day 0. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Pneumococcal Vaccine + GM-CSF | Pneumococcal Vaccine Alone | Total |
|---|---|---|---|
| Age Continuous | 70 years | 61 years | 68 years FULL_RANGE 10 |
| Region of Enrollment United States | 25 participants | 7 participants | 32 participants |
| Sex: Female, Male Female | 12 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 13 Participants | 4 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 1 / 7 |
| serious Total, serious adverse events | 0 / 25 | 0 / 7 |
Outcome results
Primary
Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine
Response defined as 2-fold rise in anticapsular immunoglobulin G (IgG) when prevaccination titer is compared with levels post vaccination and with a final level of \>0.5 ug/mL. Anti-pneumococcal immunoglobulin titers measured at baseline and 1 month after vaccine. Response determined by measuring serum IgG to capsular polysaccharides from 6 of the most common infecting serotypes of Streptococcus pneumoniae.
Time frame: Baseline and at 1 month after vaccine.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 4 | 0 participants | 5 |
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 6B | 1 participants | — |
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 9V | 1 participants | — |
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 14 | 2 participants | 66 |
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 19F | 2 participants | — |
| Pneumococcal Vaccine + Pre Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 23F | 2 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 23F | 1 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 4 | 0 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 14 | 2 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 19F | 0 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 6B | 1 participants | — |
| Pneumococcal Vaccine + Post Vaccine GM-CSF | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 9V | 1 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 6B | 0 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 9V | 1 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 23F | 1 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 14 | 0 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 4 | 1 participants | — |
| Pneumococcal Vaccine Alone | Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine | Pneumococcal Serotype 19F | 1 participants | — |