Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma (NCT03035331), a na phase 1, phase 2 study. The primary outcome is Percentage of Complete Responses of Combination Therapy With Pembrolizumab, Cryoablation, and Intra-tumor Injection of Autologous Dendritic Cells (DC) at Maximum Tolerated Dose (MTD) Dose.

2. Clinical Question

In statistical terms, this is a question about the observed proportion of evaluable participants who met the complete-response definition at the specified dose and timeframe. Without a posted numerator, denominator, response definition details, or confidence interval, the size and precision of that proportion cannot be assessed from the registry record. Nor can the contribution of any individual component be separated: the treatment is a combination, and there is no comparator group in the listed design.

3. Trial Design

This completed study is registered as phase I and phase II and uses a single-group model. Allocation is listed as NA and masking as none. The enrollment is 11. The registry names Mayo Clinic as sponsor. The recorded start date is 2017-08-15, and the primary completion date is 2022-01-25.

The treatment is described as pembrolizumab together with cryosurgery and intratumoral dendritic cell therapy. The arm description states that pembrolizumab is given intravenously and dendritic cell therapy is injected intratumorally on specified treatment days; it also specifies a schedule of repeated pembrolizumab treatment. The recorded description is truncated after the start of the cryosurgery details, so the complete treatment schedule is not reported in the registry record. The brief summary presents the study as examining dose and side effects as well as the combined treatment approach.

A single-group design can describe outcomes among participants receiving the study regimen, but it does not supply a concurrent control for estimating what would have occurred under another treatment. Because the registry lists no randomized allocation, the enrolled participants cannot be interpreted as randomized treatment arms. The dose-level safety records are separated into Phase 1 Dose Level 1 and Phase 2 Dose Level 1, but these entries do not constitute a like-for-like control comparison.

The record lists 11 outcome measures, including progression-free survival, treatment-free survival, duration of response, disease-free survival rate, overall survival, adverse events, and quality of life. It lists no analyses. Detailed eligibility criteria, the number evaluated for the primary endpoint, and the disposition of participants are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: All eligible and treated phase 1 patients are included.

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 Percentage of Complete Responses of Combination Therapy With Pembrolizumab, Cryoablation, and Intra-tumor Injection of Autologous Dendritic Cells (DC) at Maximum Tolerated Dose (MTD) Dose, measured over 24 months.

The primary endpoint is the percentage of patients with a complete response to the combination of pembrolizumab, cryoablation, and intratumoral injection of autologous dendritic cells at the maximum tolerated dose. Its stated timeframe is 24 months. The registry describes the proportion as the number of successes divided by the total number of evaluable patients and says confidence intervals for the true success proportion will be calculated.

A complete-response proportion is a binary-outcome summary: each evaluable participant is classified according to whether the defined response was achieved, and the resulting count is expressed relative to the evaluable group. Such an endpoint provides a direct description of how often the specified outcome occurred in the study population. A confidence interval is useful because a proportion estimated in a study does not by itself show how much uncertainty surrounds the estimate.

The endpoint is tied to the maximum tolerated dose, but the registry record does not report the dose selected, the number of participants evaluated at that dose, the complete-response count, the response criteria, or the calculated proportion and interval. Consequently, the endpoint's stated purpose can be explained, but its observed value and precision cannot be interpreted from the posted registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage, which is appropriate for a binary event such as whether a participant achieved a complete response under the endpoint definition. In general, estimating a percentage requires a count of participants meeting the event definition and a denominator of participants included in the analysis. The registry describes this as successes divided by evaluable patients. It does not post either count, so the endpoint cannot be independently described numerically from the record.

What does a confidence interval convey?

In general, a confidence interval communicates the uncertainty associated with an estimated population value. An estimate based on a limited amount of data can be compatible with a range of underlying values; the interval makes that uncertainty visible rather than presenting the estimate as exact. The registry says confidence intervals for the true success proportion will be calculated. The method used to construct them and the resulting interval are not reported in the registry record. Without the interval, the precision of any primary-response estimate cannot be assessed.

What is the role of the denominator?

The denominator is central to interpreting a percentage. The endpoint description specifies evaluable patients, whereas enrollment is recorded as 11. The record does not say whether every enrolled participant was evaluable for the primary endpoint. It also does not report exclusions, incomplete assessments, or the analysis population definition. It would be inappropriate to treat enrollment as the endpoint denominator without that information. In general, a different denominator can change the meaning of a reported proportion, especially when outcome status is unavailable for some participants.

What can a single-group analysis estimate?

A single-group study can describe outcomes observed among participants receiving the regimen. It does not, by itself, estimate a difference against an untreated group or another regimen. General statistical comparisons require a clearly defined contrast between groups, and causal interpretation also depends on design and assumptions. The registry lists a single-group model, allocation as NA, and no masking. It describes no randomized comparator. Therefore, the primary endpoint, if reported, would be interpreted as a response proportion in the analyzed study group rather than as a comparative treatment effect.

What do the phase and dose-level entries mean?

The safety record separates Phase 1 Dose Level 1 from Phase 2 Dose Level 1. These labels identify the groupings used for the posted safety counts. They do not establish that the groups were randomized or otherwise exchangeable. General comparisons across groups can be affected by differences in who entered each group, treatment exposure, follow-up, and outcome ascertainment. The registry does not provide analyses adjusting for such factors, and the design is not listed as a randomized comparison.

What analysis plan is documented?

The primary endpoint description states that the success proportion will be estimated and that confidence intervals will be calculated. It does not specify the interval procedure, a hypothesis test, a model, covariate adjustment, or a detailed analysis population. The registry lists 11 outcome measures and no analyses. Interim analyses, stopping rules, and a detailed statistical analysis plan are not reported in the registry record. Their absence from the record does not show what may have been done outside the posted registry information; it means those details cannot be assessed from this record.

How should planning illustrations be read?

In general, a sample-size illustration is a planning calculation, not an observed result or evidence that an analysis had a particular probability of success. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. It also distinguishes participant counts per arm from total event counts for time-to-event calculations. These are described as planning illustrations computed from an observed effect, not as the trial's own design. Because the record provides no primary effect estimate or analysis result, the numerical implications of those assumptions cannot be evaluated from the registry record. Such illustrations should not be interpreted as observed power or as a substitute for the trial's design rationale.

General statistical interpretation also depends on the outcome definition, follow-up, missingness, and consistency of measurement. For this trial, the record identifies the endpoint and timeframe but does not report the response criteria, endpoint data, or missing-data handling. Those omissions prevent a full assessment of reproducibility and robustness.

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("Phase 1 Dose Level 1", "Phase 2 Dose Level 1")
n      <- c(3, 8)
events <- c(0, 0)
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  Phase 1 Dose Level 1  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase 2 Dose Level 1  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, spanning response and time-to-event outcomes, safety, and quality of life. When a study evaluates multiple outcomes, general statistical practice distinguishes the primary question from secondary or exploratory questions and considers whether testing across outcomes could increase the chance of a false-positive finding. The record identifies a primary endpoint, but a multiplicity strategy, hierarchy for secondary outcomes, or adjustment procedure is not reported in the registry record. No outcome analyses are listed, so it is not possible to assess how multiple outcomes were handled in reported results.

Missing-data handling is also not reported in the registry record. The primary endpoint description refers to evaluable patients, but does not define evaluability or explain how participants without an assessable response were treated. The record does not report the number evaluated, the number with missing endpoint status, reasons for missingness, or any sensitivity analysis. These details are important because the observed percentage depends on which participants are counted in its denominator.

The analysis populations are not described beyond the endpoint's reference to evaluable patients. The record does not say whether the primary analysis included all enrolled participants, those who received treatment, or another defined group. It also does not report an analysis population for safety or secondary outcomes. No interim analyses, stopping rules, or complete statistical analysis plan are reported in the registry record. Accordingly, the primary endpoint's intended calculation is described at a high level, but the procedures for missing data, multiple outcomes, and analysis-population selection cannot be evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lung infection (12.5%), rash maculo-papular (12.5%).

The registry reports adverse-event counts separately for Phase 1 Dose Level 1 and Phase 2 Dose Level 1. In Phase 1 Dose Level 1, 3 participants were at risk for the serious-event listing and 0 were affected; 3 were at risk for other adverse events and 3 were affected; deaths are recorded as 1. In Phase 2 Dose Level 1, 8 were at risk for serious events and 2 were affected; 8 were at risk for other adverse events and 8 were affected; deaths are recorded as 4.

These are descriptive entries, not evidence of a between-group difference. The registry record does not report event timing, duration, attribution to treatment, recurrence, or the relationship between event counts and deaths. It also does not establish whether individual participants experienced more than one event. The top serious terms are Lung infection and Rash maculo-papular, each listed as 12.5%. The record does not explain further details about how these terms were selected or counted. The reported counts should be understood as posted safety data, not as a complete causal assessment.

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

The record establishes that the study was completed, enrolled 11 participants, and specified a complete-response percentage as its primary endpoint. It describes the endpoint timeframe as 24 months and states that a confidence interval for the true success proportion would be calculated. It also posts safety counts by phase and dose level, as well as a list of secondary outcomes.

It does not report the primary-response count, the denominator of evaluable participants, the response percentage, or its confidence interval. No outcome analyses are listed. Therefore, the registry record does not allow readers to determine the observed response proportion or its statistical precision. It also does not report the results of the listed progression-free survival, treatment-free survival, duration-of-response, disease-free survival, overall-survival, or quality-of-life outcomes.

Even if a response result were available, the single-group design would limit interpretation to outcomes observed in the treated group. Without a comparator, the study cannot provide a randomized estimate of how the combination compares with another treatment. And because several therapies are given together, a group-level outcome would not separate the effect of each component.

These limitations do not negate the descriptive information the record contains. They define its scope. Safety counts and endpoint definitions are useful for understanding what was recorded, but they do not replace outcome estimates, analysis details, or comparative evidence. No conclusion about treatment benefit or lack of benefit follows from the absence of posted efficacy results.

14. Why This Trial Matters Statistically

This trial raises several important statistical issues for clinical researchers. First, it illustrates the distinction between specifying an endpoint and reporting its result. The registry defines a complete-response proportion, names a timeframe, and describes an intended confidence interval calculation. Yet without the response count, evaluable denominator, estimate, or interval, readers cannot assess either the observed outcome or its precision.

Second, a single-group design makes the estimand descriptive rather than comparative. A proportion among participants receiving the combination may characterize that group, but it does not by itself reveal what would have happened under another treatment. The listed combination also means that any group-level result would concern the regimen as a whole, rather than identifying the contribution of each component.

Third, the gap between enrollment and the endpoint's evaluable population is statistically consequential. Enrollment is 11, while the number contributing to the primary endpoint is not reported. Clear reporting of analysis populations and missing outcomes is needed to interpret a proportion and judge whether the denominator represents the participants the research question intended to address.

Finally, the registry lists multiple outcomes and safety entries but no analyses. This makes it difficult to assess endpoint hierarchy, multiplicity, precision, and consistency across outcomes. The record is therefore a useful example of why design labels, endpoint definitions, and outcome data must be considered together. A completed status is not equivalent to a complete statistical report.

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 limitation for interpreting efficacy is that the registry record does not report the complete-response result. The success count, evaluable denominator, response proportion, and confidence interval are absent. Although the endpoint timeframe is stated as 24 months, assessment details and response criteria are not reported in the registry record.

The enrollment is 11, but the endpoint analysis population and participant disposition are not described. The record does not state how missing or unevaluable responses were handled. It also lists no outcome analyses, so the secondary outcomes cannot be interpreted from posted results.

The design is single group, with allocation listed as NA and masking as none. No comparator is described, limiting the ability to estimate a treatment contrast. The study combines pembrolizumab, cryosurgery, and dendritic cell therapy, so the separate contributions of those components cannot be identified from a group-level outcome. The arm description is truncated, and the complete treatment schedule is not reported in the registry record.

The record does not report a detailed statistical analysis plan, multiplicity handling, interim analyses, or stopping rules. Safety entries provide counts by phase and dose level, but do not describe timing, duration, treatment attribution, overlap among events, or the relation between events and deaths. These limitations constrain interpretation of both efficacy and safety without implying any particular unreported result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma — NCT03035331.
• Registry record last updated 2026-05-04; status last verified 2024-12.
• Results first posted 2025-05-16.
• 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

NCT03035331 is a completed phase I/II, single-group study sponsored by Mayo Clinic. Enrollment was 11. The recorded start date is 2017-08-15 and primary completion date is 2022-01-25. The study concerns pembrolizumab, cryosurgery, and intratumoral dendritic cell therapy for non-Hodgkin lymphoma.

The primary endpoint is the percentage of complete responses at the maximum tolerated dose, with a stated timeframe of 24 months. The registry describes estimating successes among evaluable patients and calculating confidence intervals, but does not report the endpoint result or any analyses. Safety counts are listed for two phase and dose-level groups. The record lists 11 outcome measures and no analyses.