Id-KLH Vaccine + T Cells in Subjects With Myeloma Undergoing Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Id-KLH Vaccine + T Cells in Subjects With Myeloma Undergoing Transplant (NCT01426828), a randomized phase 2 study. The primary outcome is Participants With Id-specific Immunity.

2. Clinical Question

The trial asks whether infusions of Id-KLH-primed CD3/CD28-activated autologous lymphocytes are associated with a more intense Id-specific immune response than infusions of non-Id-KLH-primed activated autologous lymphocytes. The primary outcome focuses on whether a participant met a specified immune-response definition after vaccination, rather than on a clinical disease outcome.

The immune-response definition required induction of effector-associated genes TBX21 and KLRG1, and the memory-associated gene CCL5, in CD8 T cells at post-vaccine time points compared with baseline. The stated objective is therefore specific to an immune marker definition and a comparison between vaccine-priming strategies. The record does not report a primary question about disease control, survival, or another clinical outcome.

3. Trial Design

This is a randomized, phase II, parallel-group trial with no masking. The record identifies University of Pennsylvania as the sponsor. It lists multiple myeloma as the condition and describes participants as undergoing autologous transplant. Enrollment is reported as 40. The study status is completed; the recorded start is 2011-08 and primary completion is 2016-06.

The two arms share an infusion of CD3/CD28-activated autologous lymphocytes and differ in the vaccine administered subcutaneously. Arm A received KLH-only vaccine, while Arm B received Id-KLH vaccine. The primary objective is to compare the immune response associated with Id-KLH-primed cells against the response associated with non-Id-KLH-primed cells.

For the primary outcome, the registry reports 8.0 participants in Arm A and 8.0 in Arm B. It reports a count of 0.0 meeting the endpoint in Arm A and 8.0 in Arm B. These outcome counts do not account for the full enrollment of 40, and the registry record does not explain the difference between overall enrollment and the participants represented in this outcome.

The record does not report the randomization procedure, allocation concealment, the timing or method of treatment assignment, or the reasons participants may not appear in the primary outcome counts. It also does not report protocol deviations or a detailed analysis population. These omissions limit assessment of how the trial was conducted and how the recorded outcome participants relate to all enrolled participants.

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.

Overall Study Evaluations

Immune Response Analysis

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.

6. Primary Endpoint

The registry lists the primary outcome as Participants With Id-specific Immunity, measured over 180 DAYS.

The primary endpoint is the count of participants with Id-specific immunity, assessed through 180 DAYS. The registry defines a participant as meeting the endpoint when post-vaccine CD8 T cells show induction of the effector-associated genes TBX21 and KLRG1 and the memory-associated gene CCL5, compared with baseline. RNA was isolated from CD4 and CD8 T cells before vaccination and at day 30, 90 and 180 after vaccination. Gene expression was measured with the Nanostring Human immunology V2 kit and an nCounter digital analyzer. The kit covers 594 genes involved in the human immunology response.

This endpoint translates a laboratory gene-expression criterion into a participant-level count. It is used to assess whether the vaccine-priming strategy is associated with the specified Id-directed immune signal. It is not a measure of tumor response, survival, or clinical benefit; those outcomes are not identified as the primary endpoint in the registry record.

Using a participant count makes the endpoint straightforward to describe as meeting or not meeting the stated definition. However, the definition depends on gene-expression patterns across post-vaccine measurements relative to baseline. The registry does not report further detail on thresholds, adjudication, handling of incomplete measurements, or whether any alternative definitions were considered. Those details would help readers assess how consistently the endpoint can be reproduced and how sensitive it may be to measurement decisions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is randomized and uses parallel groups. Random assignment is intended, in general, to make treatment groups comparable on average with respect to measured and unmeasured characteristics. The registry record does not describe how the random sequence was generated, how allocation was concealed, or whether randomization was stratified. Masking is listed as none, so the study is recorded as unmasked. The record does not describe whether outcome assessment or laboratory analysis was blinded.

What does the reported endpoint count represent?

The primary endpoint is binary at the participant level: a participant either met the stated gene-expression definition of Id-specific immunity or did not. The posted arm results are reported as counts. The registry lists 8.0 participants in each arm, with 0.0 meeting the endpoint in Arm A and 8.0 in Arm B. These are descriptive counts. The registry record reports no statistical analysis for the comparison and does not provide a test statistic, p-value, confidence interval, or adjusted estimate.

In general, a two-group analysis of a binary endpoint can compare the proportion meeting the definition in each group, or estimate a relative or absolute contrast, depending on the selected method. The choice of method matters because sparse counts and very uneven outcome patterns can make some standard approximations unreliable. Here, the registry’s analysis outputs do not include a two-arm comparison: the reported reason is that values are missing or not estimable for a two-arm comparison of a binary endpoint. No recalculated comparison is reported. The record therefore gives no basis for choosing among inferential methods or interpreting a particular test.

Why can a confidence interval matter?

In general, a confidence interval conveys the precision of an estimated effect and the range of values compatible with the data under the assumptions of the method. An observed count contrast alone does not communicate that uncertainty. Because no interval or comparative estimate is reported, the precision of the arm contrast cannot be assessed from the registry results. The imbalance in endpoint counts is visible descriptively, but it does not substitute for an uncertainty estimate.

What do the sample-size assumptions describe?

The record describes a planning illustration based on the observed effect, not the trial’s original design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For a binary endpoint, the record says that the relevant two-arm values are missing or not estimable. The numerical planning results and any original sample-size justification are not reported in the registry record. These planning illustrations, where available, would be hypothetical planning quantities rather than observed power or a measure of the trial’s evidential strength.

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect an effect using a chosen design and statistical method. It does not show that a completed trial had that level of power, and it cannot repair missing outcome information. The record does not report the rationale used to set the enrollment of 40, the target effect size, or whether the study’s original design assumptions matched the later planning illustration.

What limits interpretation of gene-expression measurements?

The record describes RNA collection from CD4 and CD8 T cells before vaccination and at day 30, 90 and 180 after vaccination. It names the assay platform and the genes used in the participant-level definition. In general, a prespecified endpoint definition helps readers understand how measurements are converted into an outcome. The record does not report expression thresholds, details of normalization, how measurements at different post-vaccine times were combined, or rules for missing or unusable assays. It also does not report whether the endpoint definition was finalized before examining the results.

These gaps matter because a participant-level classification may depend on both assay quality and choices about how to interpret repeated measurements. The registry record does not provide enough methodological detail to assess those decisions. It also does not report an adjusted analysis, a sensitivity analysis, or a detailed analysis population. Consequently, the posted counts can be described, but their statistical uncertainty and robustness to analytic choices cannot be evaluated from the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Arm A", "Arm B")
n      <- c(8, 8)
events <- c(0, 8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm A  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  Arm B  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary outcome measure and no secondary outcomes posted. It does not report an analysis for the primary outcome; the recorded number of analyses is zero. A multiplicity strategy, such as how testing across multiple outcomes or time points would be controlled, is not reported in the registry record. Although the primary endpoint incorporates gene-expression information at post-vaccine time points, the record does not explain whether each time point was analyzed separately, combined under a prespecified rule, or treated as part of a single participant-level classification.

In general, multiplicity arises when multiple hypotheses or outcomes are examined, because repeated testing can increase the chance of a false-positive finding. A prespecified analysis plan can clarify which comparison is primary and how secondary or exploratory results should be interpreted. The registry does not report such a plan or an adjustment for multiple comparisons. No claim about the handling of multiplicity can therefore be made from the posted record.

The primary outcome counts include 8.0 participants in each arm, compared with an overall enrollment of 40. The registry does not report why the other enrolled participants are not represented in these counts, the number with missing measurements, or any imputation or missing-data procedure. It does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not state whether participants were excluded from the endpoint assessment or how incomplete gene-expression data affected endpoint classification.

In general, missing outcome data can affect both the number of observations available and the interpretation of a comparison, particularly if missingness differs between arms or relates to the outcome. The registry does not report enough information to assess those possibilities. The relationship between the outcome counts and the randomized population is therefore unclear.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (5.6%), febrile neutropenia (5.6%), fever (5.6%), nausea (5.6%), neutrophil count decreased (5.6%).

The registry reports serious adverse events for 22 participants at risk in Arm A and 18 at risk in Arm B. The corresponding counts affected are 6 in Arm A and 4 in Arm B. It reports 0 deaths in each group. For other adverse events, the record lists 22 at risk and 20 affected in Arm A, and 18 at risk and 16 affected in Arm B. These figures describe the safety groups as recorded; they are not the primary immune-response endpoint.

The listed serious adverse-event terms are Dehydration, Febrile neutropenia, Fever, Nausea, Neutrophil count decreased, and Platelet count decreased. Each term is listed with 5.6%. The registry record does not clarify in this summary whether participants could experience more than one listed term, how the term percentages were calculated, or the timing and duration of events. These term-level percentages should not be added together or interpreted as a count of distinct participants.

In general, safety counts describe events observed under the registry’s reporting definitions; they do not by themselves establish that an intervention caused an event. The groups differ in the reported number at risk, and no comparative safety analysis or uncertainty estimate is reported. The figures should therefore be read as descriptive reports rather than as a quantified comparison of risk between arms.

13. What the Result Does, and Does Not, Mean

The posted results show a difference in the number of participants meeting the specified Id-specific immunity definition: the registry reports 0.0 in Arm A and 8.0 in Arm B, with 8.0 participants recorded for the primary outcome in each arm. The result is a count-based description of an immune marker endpoint. It does not include a reported estimate of the comparative effect or its precision.

The result does not establish that the same pattern would occur among all randomized participants. Overall enrollment is 40, and the record does not explain why the primary outcome is reported for 8.0 participants per arm. It does not describe missingness, exclusions, or the analysis population. Those omissions prevent a clear assessment of how the recorded participants relate to the full trial population.

The result also does not answer whether the immune marker pattern affected myeloma, transplant outcomes, survival, or another clinical endpoint. The registry identifies gene-expression changes in CD8 T cells as the basis for classifying participants, rather than reporting those clinical outcomes as the primary measure. No medical conclusion should be drawn from the immune marker counts alone.

In general, a randomized comparison is most informative when outcome definitions, analysis populations, missing-data handling, and comparative estimates are reported. Here, the registry describes randomization and the endpoint definition, but no inferential analysis is posted. The reader can observe the outcome counts but cannot assess a confidence interval, p-value, or sensitivity of the result to analytic assumptions.

The finding is therefore best understood as a marked descriptive contrast in the small set of participants represented in the primary outcome record. It is not, by itself, evidence about clinical efficacy, the response of all enrolled participants, or the precision of a treatment effect. The registry record does not report the additional analyses needed to address those questions.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between a clear descriptive pattern and a complete comparative analysis. The recorded primary outcome counts are sharply separated across the arms, yet the registry reports no inferential analysis and no uncertainty estimate. Readers can identify what was observed among the participants represented, but cannot use the record to judge the precision of a comparison or its compatibility with alternative effects.

The discrepancy between overall enrollment of 40 and 8.0 participants per arm in the outcome record is also important. A trial result is easier to interpret when the path from randomized participants to analyzed participants is explicit. The registry does not report that path, the analysis population, or missing-data handling. This makes the completeness and representativeness of the primary endpoint counts difficult to assess.

The endpoint also highlights a distinction between biological measurement and clinical outcome. The trial operationalizes an immune response through a gene-expression definition in CD8 T cells, using measurements at specified post-vaccine times relative to baseline. That endpoint addresses the stated immunologic question, but it does not itself establish a relationship with clinical outcomes. Clear interpretation requires keeping the measured endpoint separate from outcomes not reported in the primary result.

In general, reporting the analysis plan, endpoint rules, participant flow, and uncertainty estimates allows readers to distinguish the observed data from claims that depend on statistical assumptions. The record’s omissions make that distinction especially relevant. The posted counts remain informative as a description of the recorded observations, while the absence of inferential and population details limits broader conclusions.

15. 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.

The primary outcome is available for 8.0 participants in each arm despite a total enrollment of 40. The registry record does not explain why the outcome counts cover only these participants, how they were selected, or whether missing measurements or exclusions account for the difference. Without participant flow and an identified analysis population, it is not possible to assess how representative the counts are of the randomized groups.

No inferential analysis is reported. The registry provides no comparative estimate, confidence interval, p-value, or statistical model for the binary endpoint, and it notes that values are missing or not estimable for a two-arm comparison. The magnitude and precision of a comparison therefore cannot be assessed using the posted analysis record.

The endpoint definition relies on gene-expression changes at post-vaccine time points compared with baseline, but detailed thresholds, assay quality procedures, rules for combining repeated measurements, and handling of incomplete measurements are not reported. The record also does not describe whether the endpoint definition or analysis choices were specified before the results were known.

Details about the randomization procedure, allocation concealment, and blinding of laboratory or outcome assessment are not reported. A multiplicity plan and adjustment strategy are also not reported, despite measurements across multiple genes and post-vaccine times. The registry does not provide an original sample-size justification or a detailed statistical plan.

Finally, the primary endpoint is an immune marker classification. The registry does not report a primary clinical outcome such as disease response or survival, and the immune marker result cannot answer those questions on its own. These limitations restrict interpretation to the recorded endpoint counts and safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Id-KLH Vaccine + T Cells in Subjects With Myeloma Undergoing Transplant — NCT01426828.
• Registry record last updated 2020-12-04; status last verified 2020-12.
• Results first posted 2020-12-04.
• 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.

19. Record Summary

NCT01426828 is a completed randomized phase II parallel-group trial sponsored by University of Pennsylvania. It enrolled 40 subjects with multiple myeloma undergoing autologous transplant and was unmasked. Arm A received activated autologous lymphocytes with KLH-only vaccine; Arm B received activated autologous lymphocytes with Id-KLH vaccine.

The primary outcome was the count of participants meeting a gene-expression definition of Id-specific immunity through 180 DAYS. The record reports 8.0 participants per arm for this outcome, with 0.0 meeting the definition in Arm A and 8.0 in Arm B. No inferential analyses are reported, and the registry record does not explain why the outcome counts represent only 8.0 participants per arm despite enrollment of 40.

Safety summaries list serious and other adverse-event counts and 0 deaths in each group. The registry does not report a comparative safety analysis, a detailed statistical plan, or how missing primary outcome data were handled.