This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Immuno-Augmentation With GM-CSF of Pneumococcal Vaccine in Chronic Lymphocytic Leukemia Patients (NCT00323557), a randomized phase 2 study. The primary outcome is Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00323557 |
| Phase | Phase 2 |
| Condition | Leukemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns patients with chronic lymphocytic leukemia (CLL) receiving treatment for advanced CLL, as described in the official title. The registry record does not report further eligibility details, such as age ranges, disease characteristics, or prior treatment requirements. It lists enrollment as 39, but the available endpoint information does not identify how many participants contributed results to each analysis.
Intervention
The intervention arm received pneumococcal vaccine with sargramostim, also called GM-CSF. The arm description says three doses of 250 mg were given subcutaneously, either before vaccination on Day -7, Day -1 and Day 0, or after vaccination on Day 0, Day +3 and Day +7. The record does not specify how participants were assigned between the pre-vaccine and post-vaccine schedules.
Comparator
The comparator arm received pneumococcal vaccine alone, with the first vaccine dose given subcutaneously on Day 0. The study therefore compares vaccine plus GM-CSF with vaccine alone, while the GM-CSF schedule within the combined-treatment description includes pre-vaccine and post-vaccine timing options. Further details about the assignment of those timing options are not reported in the registry record.
Primary question
The primary endpoint concerns the number of participants with an immune response, assessed at baseline and 1 month after vaccine. Response was defined using a 2-fold rise in anticapsular IgG and a final level >0.5 ug/mL. The record does not report the group-specific endpoint counts or an analysis comparing the groups. The central question is therefore clear from the trial design, but its primary statistical result cannot be evaluated from the registry record.
3. Trial Design
This was a phase 2, randomized, parallel-group trial with no masking. Its stated enrollment is 39, and its status is completed. The registry lists M.D. Anderson Cancer Center as sponsor. The study dates are recorded as starting in 2004-06, with primary completion in 2011-05.
The two named arms were Pneumococcal Vaccine + GM-CSF and Pneumococcal Vaccine Alone. The first arm combined pneumococcal vaccine with sargramostim, while the comparator received vaccine without GM-CSF. The record describes GM-CSF as three subcutaneous doses of 250 mg, administered either before vaccination or after it. It does not identify the number assigned to each GM-CSF timing schedule, or explain how that timing was allocated.
Randomization means that treatment assignment was intended to use a chance-based process. The registry does not report the sequence-generation method, allocation concealment, or whether any stratification was used. With no masking, participants and study personnel were not masked to treatment assignment according to the recorded design. The record does not explain whether outcome assessors or laboratory personnel were masked.
The parallel-group structure assigns participants to a treatment arm for comparison rather than describing a crossover. The primary outcome is an immune-response count assessed at baseline and 1 month after vaccination. Although the registry lists an enrollment figure and arm descriptions, it does not report participant flow, endpoint-specific analysis populations, or group-specific primary outcome results. The trial is marked completed, but completion status alone does not indicate what the outcome estimates were or how precisely they were measured.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 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.
Overall Study
| Stage | Pneumococcal Vaccine + GM-CSF | Pneumococcal Vaccine Alone |
|---|---|---|
| STARTED | 25 | 7 |
| COMPLETED | 24 | 7 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Pneumococcal Vaccine + GM-CSF | Pneumococcal Vaccine Alone |
|---|---|---|
| Physician Decision | 1 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Pneumococcal Vaccine + GM-CSF | Pneumococcal Vaccine Alone | Total |
|---|---|---|---|---|
| Participants analysed | 25 | 7 | 32 | |
| Age Continuous | years | 70 (51 to 91) | 61 (57 to 77) | 68 (full range 10) |
| Sex: Female, Male: Female | Participants | 12 | 3 | 15 |
| Sex: Female, Male: Male | Participants | 13 | 4 | 17 |
| Region of Enrollment: United States | participants | 25 | 7 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants (With Increase) Immune Response to GM-CSF With a Pneumococcal Vaccine, measured over Baseline and at 1 month after vaccine..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants meeting the registry’s definition of an immune response to pneumococcal vaccine. The description calls for measuring serum IgG against capsular polysaccharides from 6 of the most common infecting serotypes of Streptococcus pneumoniae. Titers are measured at baseline and 1 month after vaccination.
A participant was defined as having a response when the prevaccination titer rose 2-fold and the final level was >0.5 ug/mL. This rule turns laboratory measurements into a participant-level outcome: each assessed participant either meets the stated response definition or does not. The registry names GM-CSF in the endpoint title, while its description defines the response using antibody levels after pneumococcal vaccination.
In general, an antibody-response endpoint can be used to assess whether a vaccine-associated immune marker changes according to a prespecified threshold. Such an endpoint is not itself a measure of clinical illness or prevention of disease. The registry record does not report group-specific response counts, estimates of the difference between treatment groups, or uncertainty intervals. Consequently, the endpoint definition can be described, but its observed comparative result cannot be interpreted from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of pneumococcal vaccine plus GM-CSF against pneumococcal vaccine alone in patients with CLL. It also gives a specific laboratory-based definition of immune response and a follow-up time of 1 month after vaccination. These details establish what the study intended to compare and how its primary outcome was defined.
The primary outcome results are not reported in the registry record. In particular, the record does not give the number of participants meeting the response definition in either arm, an estimated treatment contrast, or a confidence interval or p-value. It lists one outcome measure, but no outcome analyses are reported. Without the group results, there is no basis in this record for describing the direction, magnitude, or statistical precision of the primary comparison.
The enrollment figure of 39 should not be treated as the analysis population for the primary endpoint. The record does not provide participant flow or show how many participants had usable baseline and follow-up antibody measurements. The adverse-event risk denominators are different from the enrollment figure, but they refer to safety records and do not establish the endpoint analysis denominators.
The completed status indicates that the registry marks the trial as completed; it does not supply the missing primary outcome results. Likewise, the randomized design does not by itself establish that a treatment contrast was estimated or that the reported record contains enough information to assess it. The result needed for interpretation would include the response counts by arm and an appropriate comparison with uncertainty. Those items are not reported in the registry record.
The safety entries can be read separately from the primary endpoint. The record lists 0 serious adverse events among 25 at risk in the vaccine-plus-GM-CSF arm and 0 among 7 at risk in the vaccine-alone arm. It also lists other adverse events for the groups. These entries describe recorded safety counts, not antibody responses; they do not fill the gap in the primary efficacy outcome information.
Any sample-size values displayed with the analysis are planning illustrations based on the stated assumptions, not observed power. The assumptions describe two-sided significance level 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. The observed effect itself is not reported in this registry record, so the planning assumptions should not be mistaken for a reported primary result.
9. Statistical Methods Explained
The methods that can be identified from the registry record are limited. The study is described as randomized, unmasked, and parallel-group. Its primary outcome is a participant count based on a binary response definition. The record does not provide a statistical analysis plan, a primary contrast estimate, or outcome-level analyses. The following explains general statistical ideas relevant to this design without attributing unreported methods to the investigators.
What does randomization contribute?
In general, randomization uses chance to assign participants to treatment groups. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that may not have been measured. Randomization does not guarantee that groups will be identical, particularly in a study with limited enrollment. It also does not resolve problems that arise after assignment, such as missing outcome measurements or departures from assigned treatment.
The registry states that allocation was randomized, but the method used to generate assignments and conceal them before assignment is not reported in the registry record. Those details matter because they help readers assess whether the allocation process could have been anticipated or influenced. The record also does not state whether assignment was stratified by any participant characteristic.
How should a binary outcome be understood?
In general, a binary endpoint classifies each assessed participant into one of two outcome states. Here, the response state is defined by the antibody criteria in the registry record: a 2-fold rise from the prevaccination titer and a final level >0.5 ug/mL. A group’s response count depends on both the number meeting the definition and the number whose measurements were assessed. Without both the counts and analysis denominators, a reader cannot reconstruct or evaluate the group comparison.
Binary outcomes can be compared using measures such as a difference in response proportions, a ratio of response proportions, or a model-based estimate. These are general options, not methods attributed to this trial. The registry record does not identify which measure, if any, the investigators used. It does not report adjustment for covariates or the handling of measurements that could not be classified under the response rule.
What does statistical precision mean?
In general, a confidence interval describes a range of values compatible with the data and a specified statistical procedure. Its width conveys precision: a narrower interval indicates greater precision under that procedure, while a wider interval indicates more uncertainty. A point estimate without an interval does not communicate the full uncertainty in the result. No confidence interval or primary estimate is reported in the registry record, so statistical precision for the immune-response comparison cannot be assessed.
A p-value, in general, measures how unusual data at least as extreme as those observed would be under a specified null model. It does not measure the probability that a treatment works, nor does it describe the size or clinical importance of an effect. The registry record does not report a p-value for the primary endpoint. The absence of that value should not be filled in by inference from the study design or its completion status.
What can be learned from the planning assumptions?
The record describes sample-size illustrations using a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that a planned effect was observed or that the trial had a particular achieved power. The record does not give the observed primary effect, and no sample-size illustration values are included in the registry information. A planning calculation is conditional on its assumptions; it is not a substitute for the actual treatment estimate and its uncertainty.
In general, over-dispersion is relevant when observed variability exceeds what a chosen statistical model expects. It can make standard errors too small if ignored, leading to intervals that are too narrow and tests that are too optimistic. The registry record does not report a model for the primary endpoint or indicate that over-dispersion was assessed. No claim about the use or relevance of such a correction can therefore be made for this trial.
What is not specified?
The registry record does not report the primary analysis population, how missing antibody measurements were handled, whether the analysis followed assigned treatment, or whether any sensitivity analyses were conducted. It does not report interim analyses, multiplicity adjustment, a sample-size justification, or a detailed statistical plan. These are not details that can be inferred from randomization, the listed outcome, or the trial’s completed status. They are important elements of interpretation because they clarify which data contributed to the estimate and how the analysis was chosen.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure, but it also flags that the primary outcome has several categories or time points and is not reduced to one comparison. The record does not specify those categories or explain which comparisons were intended to be primary. It does not report a multiplicity adjustment or a prespecified hierarchy for interpreting multiple outcome comparisons. Therefore, the number and role of any individual comparisons cannot be assessed from the registry record.
In general, examining multiple outcomes, categories, time points, or subgroup contrasts can increase the chance of finding an apparently notable result by chance. Statistical approaches for addressing this can include prespecifying a primary comparison or adjusting inference across a family of tests. These are general considerations; the registry record does not establish that either approach was used in this study. No primary analysis is reported against which to evaluate such choices.
Missing-data handling and analysis populations are also not reported in the registry record. It does not say how many participants had antibody measurements at baseline and follow-up, how incomplete records were treated, or whether participants were analyzed according to assigned group. The enrollment entry does not identify the denominator used for the primary endpoint. The safety denominators cannot be assumed to be the endpoint denominators because they describe different records.
These omissions limit assessment of potential bias and precision. If participants without follow-up measurements differed from those with complete measurements, the analyzed response counts could represent a selected subset. That is a general possibility, not evidence that it occurred in this trial. The registry record does not provide enough detail to assess whether missing measurements or multiple comparisons affected the reported conclusions, and it does not report primary conclusions to evaluate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pneumococcal Vaccine + GM-CSF | 0 | 25 | 0.0% |
| Pneumococcal Vaccine Alone | 0 | 7 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pneumococcal Vaccine + GM-CSF | 9 of 25 |
| Pneumococcal Vaccine Alone | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pneumococcal Vaccine + GM-CSF | Pneumococcal Vaccine Alone |
|---|---|---|---|
| Pain and redness at injection site | Skin and subcutaneous tissue disorders | 6 of 25 | 1 of 7 |
| Low grade fever | Investigations | 2 of 25 | 0 of 7 |
| Palmar Erythema | Skin and subcutaneous tissue disorders | 1 of 25 | 0 of 7 |
The registry lists serious adverse events as 0 among 25 at risk in the Pneumococcal Vaccine + GM-CSF arm and 0 among 7 at risk in the Pneumococcal Vaccine Alone arm. It lists other adverse events as 9 among 25 at risk in the combination arm and 1 among 7 at risk in the vaccine-alone arm. These are the recorded counts and denominators in the safety entries; they should be read as separate arm-specific figures.
The record does not list serious adverse-event terms, and deaths are not reported in the registry record. The entries do not describe severity categories beyond the serious-versus-other distinction, timing, duration, attribution, or whether events were recurrent. They also do not explain how safety follow-up was defined or why the at-risk denominators differ from the enrollment entry.
In general, a zero recorded event count does not establish that the underlying risk is zero. Small or incomplete safety datasets can leave substantial uncertainty, and event counts alone do not show whether an event was caused by a treatment. These registry entries describe what was recorded, not a comparative safety analysis. No statistical comparison or uncertainty interval for adverse events is reported.
12. What the Result Does, and Does Not, Mean
The record establishes that investigators registered a randomized, open-label phase 2 comparison of pneumococcal vaccine with GM-CSF against pneumococcal vaccine alone in patients with CLL. It defines the primary immune-response outcome using serum IgG measurements at baseline and 1 month after vaccination. It also describes the two treatment arms and reports limited adverse-event counts.
The primary outcome result is not reported in the registry record. As a result, the record does not establish how many participants met the response definition in either arm, how the groups compared, or how precise any estimated difference might be. A randomized design describes how assignment was intended to occur; it cannot replace the outcome data needed to estimate a treatment contrast.
The endpoint is an antibody-based response measure, not a reported measure of pneumococcal illness or pneumonia. The registry’s stated study goal concerns whether GM-CSF improves vaccine effectiveness, but the primary endpoint description provided in the record concerns antibody levels. Without clinical outcome results, no conclusion about prevention of disease can be drawn from this endpoint description.
The safety counts likewise have a limited meaning. They show recorded serious and other adverse-event counts for the listed at-risk groups, but do not provide detailed event descriptions or a comparative safety analysis. The counts do not by themselves establish causation, and the absence of recorded serious events in these entries should not be interpreted as proof that serious events cannot occur.
Overall, the registry record allows readers to identify the question, design, endpoint definition, and some safety counts. It does not supply the primary results needed to judge the observed immune-response comparison. No conclusion about the direction, size, statistical significance, or clinical importance of that comparison can be supported by the registry record alone.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the difference between a registered question and a reported result. The record clearly describes a randomized comparison and a threshold-based immune-response endpoint. However, without group-specific primary outcome counts or an estimated contrast, readers cannot determine what the study observed on its stated primary measure.
The case also illustrates why the definition of an endpoint is not enough to interpret it. A rule based on a 2-fold rise and a final level >0.5 ug/mL makes the classification criterion explicit. Interpretation still requires the number meeting that criterion, the relevant denominators, and a measure of uncertainty. Those elements are not reported for the primary endpoint in this registry record.
Another statistical issue is the distinction between enrollment and analysis. The record lists enrollment as 39, but does not identify the primary endpoint analysis population. The safety denominators are recorded separately and cannot stand in for the antibody analysis denominators. Clear reporting of participant flow and endpoint-specific denominators is necessary for readers to understand which data support an estimate.
Finally, the registry flags that the primary outcome has several categories or time points without reducing them to one comparison. That makes the unreported analysis plan relevant: readers would need to know which comparison was designated as primary and how any additional comparisons were handled. The record does not provide those details. These features make the trial useful for illustrating how design information, endpoint definition, analysis choices, and reported results each contribute distinct parts of statistical interpretation.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific limitations follow from gaps in the registry record. The primary endpoint is defined, but no group-specific response counts, effect estimate, confidence interval, or p-value are reported. The absence of these results prevents assessment of the direction, magnitude, and precision of the primary comparison.
The endpoint description refers to antibody measurements at baseline and 1 month after vaccination and identifies testing against capsular polysaccharides from 6 serotypes. It does not report the distribution of measurements, the number of participants assessed at each time point, or how incomplete measurements were handled. The registry also flags several categories or time points without reducing the endpoint to one comparison, while giving no detailed analysis plan.
The intervention description includes pre-vaccine and post-vaccine GM-CSF schedules but does not state how participants were allocated between those schedules. The record does not report whether those timing options were analyzed separately or together. It also lacks details about allocation concealment, random-sequence generation, masking of outcome assessors, participant flow, and analysis populations.
The safety information is limited to event counts and at-risk denominators. Serious adverse-event terms are not listed, deaths are not reported in the registry record, and event timing, duration, attribution, and follow-up procedures are not described. These gaps limit interpretation of the safety entries. The study’s completed status and enrollment entry do not resolve these limitations or substitute for the missing outcome and analysis details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immuno-Augmentation With GM-CSF of Pneumococcal Vaccine in Chronic Lymphocytic Leukemia Patients — NCT00323557.
- Registry record last updated 2012-12-05; status last verified 2012-12.
- Results first posted 2012-05-02.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00323557 is a completed, randomized, unmasked, parallel-group phase 2 study sponsored by M.D. Anderson Cancer Center. The registry lists enrollment as 39, a start date of 2004-06, and primary completion in 2011-05. The study concerns pneumococcal vaccine with or without sargramostim in patients with CLL receiving treatment for advanced disease.
The primary endpoint is the number of participants meeting an antibody-response definition at baseline and 1 month after vaccination: a 2-fold rise in anticapsular IgG and a final level >0.5 ug/mL. The registry record does not report the primary outcome counts or a statistical comparison. Safety entries list 0 serious adverse events among 25 at risk and 9 other adverse events among 25 at risk for vaccine plus GM-CSF; for vaccine alone, they list 0 serious adverse events among 7 at risk and 1 other adverse event among 7 at risk. Deaths are not reported in the registry record.