Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia (NCT02767934), a na phase 2 study. The primary outcome is Rate of Complete Minimal Residual Disease Response.

2. Clinical Question

The clinical question concerns whether adults with acute lymphoblastic leukemia and minimal residual disease achieve a complete MRD response during treatment with pembrolizumab. The study is phase II and uses a single treatment group, so it describes outcomes among treated participants rather than comparing pembrolizumab with a concurrent control group. The registry record does not report a primary response result or an estimate of how often complete MRD response occurred.

3. Trial Design

This was a phase II study sponsored by the University of Washington. The registry describes a single-group design with an intended enrollment of 12 participants. Allocation was listed as not applicable, and masking as none. There is no randomized control group, so the trial is not a head-to-head comparison.

The study started on 2017-01-13, and its primary completion date is recorded as 2019-07-31. Its current status is terminated. The reason for termination, the date on which termination occurred, and whether all planned follow-up was completed are not reported in the registry record. The enrollment figure is an intended or recorded study enrollment count; it should not be taken as proof that every enrolled participant received treatment or contributed to every endpoint.

Participants in the treatment group received pembrolizumab intravenously over 30 minutes on day 1. Cycles were planned every 21 days for 2 years unless disease progression or unacceptable toxicity occurred. For participants achieving complete MRD response, the record allowed up to 1 additional year of treatment at the investigator’s discretion. The registry also lists laboratory biomarker analysis as an intervention, but its procedures and role in the analysis are not reported in the registry record.

The primary outcome is the rate of complete minimal residual disease response, defined in the registry as the percentage of evaluable subjects achieving a complete response, with a timeframe of up to 2 years. Overall survival and relapse-free survival are listed as secondary outcomes. The record identifies a Simon two-stage optimum design for assessing the primary endpoint, but does not give its stage sizes, response thresholds, stopping boundaries, or operational details. Other protocol features, including the planned analysis populations, 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

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 Rate of Complete Minimal Residual Disease Response, measured over Up to 2 years.

The primary endpoint is the rate of complete minimal residual disease response. The registry defines it as the percentage of evaluable subjects who achieve a complete response and gives a timeframe of up to 2 years. The outcome is expressed as a participant count in the record, but no response count or percentage is reported.

In general, minimal residual disease refers to cancer cells that remain detectable after treatment even when disease burden is small. Assessing complete MRD response can therefore describe whether residual disease is no longer detected according to the study’s response criteria. It focuses on a response state rather than on survival or time to relapse. The specific laboratory method, detection threshold, and criteria for defining a complete response are not reported in the registry record, so the endpoint cannot be independently interpreted in relation to a particular assay or threshold.

The endpoint is suited to a phase II activity assessment because it asks how often a defined response occurs among evaluable participants. The registry says that the rate will be evaluated with a Simon two-stage optimum design. In general, this type of design can use response information in stages to guide whether a study continues, but the trial’s response boundaries and stage-specific sample sizes are not reported in the registry record. Without the observed number of complete responses, the endpoint’s estimated rate and its precision cannot be assessed.

Overall survival and relapse-free survival are listed as secondary outcomes, but their definitions, analysis methods, follow-up summaries, and results are not reported in the registry record. They should not be substituted for the primary MRD response endpoint when describing what the study set out to assess.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited to the stated endpoint and a reference to a Simon two-stage optimum design. No statistical analyses are reported in the registry record. This means that interpretation must distinguish the planned method from any observed results: the method description identifies an intended approach, but it does not supply an estimate, uncertainty interval, test, or decision.

What does a response rate represent?

In general, a response rate is the share of participants in a defined analysis population who meet a prespecified response criterion. Here, the endpoint is described as the percentage of evaluable subjects who achieve complete MRD response. The word “evaluable” is important because it identifies the denominator used for the endpoint. The registry record does not define how evaluability is determined, how missing assessments are handled, or whether participants without an assessment count as nonresponders. Without those rules and the actual numerator and denominator, the response rate cannot be reconstructed or assessed.

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of its statistical method. For a response rate, it would indicate the range of values reasonably compatible with the observed response data and the chosen method. No response estimate or confidence interval is reported in the registry record, so the precision of the primary outcome is unknown. A count by itself, even if one were available, would not explain uncertainty without the relevant denominator and analysis approach.

What is the role of the Simon two-stage design?

In general, a Simon two-stage design evaluates a response endpoint in stages and can include rules for stopping early when response activity is not sufficient to justify continued enrollment. An optimum design is a design choice based on prespecified operating criteria. This general description does not establish what rules were used in this study. Although the registry names this design, it does not report the stage sizes, response thresholds, stopping boundaries, or criteria used to choose the design. It also does not report whether the planned stages were completed or whether a stopping rule was applied.

Those details are needed to interpret the design’s intended error rates and stopping behavior. They also matter when evaluating whether the analysis followed the plan. The registry’s reference to a two-stage method therefore supports only the statement that the method was named; it does not show how the trial proceeded or what decision it reached.

Why is the absence of a control group consequential?

In general, a single-group study estimates outcomes among participants receiving the study treatment. A control group can help distinguish treatment-associated outcomes from changes that could occur for other reasons. Random allocation can also reduce systematic differences between groups. This study is recorded as single-group, with no masking and no allocation to a comparator. Its results, if reported, would therefore need to be interpreted as outcomes in the treated group rather than as a controlled estimate of the treatment’s effect. Since no primary outcome results are reported, even that descriptive response estimate is unavailable.

For a randomized comparison, statistical methods can estimate the difference between groups and quantify uncertainty around that contrast. Such a treatment contrast is not available in a single-group study. A comparison with an external benchmark would require an appropriate benchmark and assumptions about comparability; no such comparison is described in the registry record.

How should planning calculations be understood?

In general, sample-size calculations depend on a target effect, a chosen error rate, allocation, and statistical assumptions. The planning illustration associated with this study is explicitly described as not being the trial’s own design. Its assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, despite the registry describing this study as single-group. It is therefore a hypothetical illustration rather than a reconstruction of the study’s phase II design. It is not observed power, and it cannot establish what the trial could detect under its actual enrollment or analysis.

Planning calculations should not be interpreted as results. They do not show that a target response occurred, nor do they replace an estimate based on observed participants. The registry record does not report the study’s own sample-size justification, so its original assumptions and rationale are unknown.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If ignored, it can make uncertainty appear smaller than it is and can affect tests or intervals. This is a general concept, not a reported feature of this study. The primary endpoint is a participant response count, and the registry record does not describe a model, any dispersion estimate, or an over-dispersion assessment. It would be inappropriate to infer that over-dispersion was present or that a particular adjustment was used.

Overall, the registry record gives enough information to identify the endpoint and the named design framework, but not enough to reproduce or evaluate a statistical analysis. The response criteria, analysis population, missing-data rules, stage-specific design parameters, and outcome estimates are not reported in 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("Pembrolizumab")
n      <- c(12)
events <- c(1)
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  Pembrolizumab  12  1  8.3  0.2  38.5  1.5  35.4  1.9  36.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists complete MRD response as the primary outcome and lists overall survival and relapse-free survival as secondary outcomes. It also records three outcome measures, but does not report their analysis results. The registry record does not describe a multiplicity plan, such as whether any adjustment or hierarchy was intended across outcomes. In general, evaluating multiple outcomes can increase the chance of a positive statistical finding by chance if each is tested separately; a prespecified strategy clarifies how the evidence is to be interpreted. No such strategy is reported.

The primary endpoint refers to evaluable subjects, but the record does not define the evaluable population. It does not specify whether the primary analysis was intended to include all enrolled participants, only participants who received treatment, or another group. The treatment exposure and analysis population for each outcome are not reported in the registry record.

Missing-data methods are also not reported. The registry does not say how participants without a response assessment would be treated in the primary analysis, how incomplete follow-up would be handled for survival outcomes, or whether sensitivity analyses were planned. These omissions matter because the handling of unobserved outcomes can affect both the denominator and the interpretation of a response estimate.

No statistical analyses are reported in the registry record. As a result, there are no reported estimates with which to assess multiplicity, missingness, or consistency across analysis populations. These are limits on interpretation, not evidence that a particular method was or was not used outside the registry record.

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: bacteremia (acinetobacter ursingii, herbasprillum, achromobacter xylosoxidans) (8.3%).

The registry lists adverse-event counts for the pembrolizumab group. There were 12 participants at risk in the serious-adverse-event summary, and 1 participant was reported as affected by a serious adverse event. For other adverse events, 12 participants were at risk and 6 were reported as affected. The record also lists 5 deaths. These are separate reported counts; the registry information does not establish whether the affected participants or deaths overlap across categories.

The most frequent serious adverse-event term listed is bacteremia, with the terms “acinetobacter ursingii, herbasprillum, achromobacter xylosoxidans” in parentheses, and a reported value of 8.3%. This term-level value is not a complete account of all serious events, and the record does not provide further event narratives or timing. The follow-up period used for the adverse-event counts is not reported in the registry record.

Counts and percentages in an adverse-event record describe reported events in the study group; by themselves they do not establish that treatment caused an event. The record does not provide a comparison group or details sufficient to assess attribution, duration, severity beyond the serious classification, or outcomes for individual events. The listed deaths should not be assumed to have been treatment-related, and the registry record does not report their causes or attribution.

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

This study asks a clinically focused question: whether complete MRD response occurs among adults with acute lymphoblastic leukemia treated with pembrolizumab. The registry identifies a phase II, single-group design, an intended enrollment of 12, and a response endpoint assessed for up to 2 years. It also identifies overall survival and relapse-free survival as secondary outcomes. These details describe the study’s purpose and structure, not its efficacy findings.

The registry record does not report a complete MRD response count or rate, confidence interval, or statistical analysis. It therefore does not establish how often participants achieved the primary endpoint or how precisely that rate could be estimated. The record also does not provide results for the listed secondary outcomes. No conclusion about the treatment’s effect can be drawn from the endpoint definition, the design label, or the fact that the study was conducted.

Because there is no concurrent comparator, any reported outcome would describe the treated group rather than demonstrate what would have happened to comparable participants under a different approach. The study design cannot, on its own, separate treatment effects from other influences on outcomes. This is a general limitation of single-group evidence, not a claim about what caused any individual outcome in this trial.

The terminated status does not explain why the study ended or whether follow-up and analyses were completed as intended. The registry record does not report a termination reason, and the design details needed to interpret the named two-stage approach are absent. The reported safety counts are also descriptive; they do not establish causation or permit a comparative safety assessment.

The most defensible reading is therefore bounded: the registry documents a phase II study of pembrolizumab for minimal residual disease, specifies its primary response question, and lists some safety counts, but does not report the efficacy analyses needed to answer that question. Lack of a reported result is not evidence of either benefit or lack of benefit.

14. Why This Trial Matters Statistically

The trial is statistically notable because it pairs a response-focused phase II question with a single-group design and a named Simon two-stage optimum design. Such a design framework is intended to assess response activity in stages, but its interpretation depends on prespecified thresholds, stage sizes, and stopping rules. Those details are not reported in the registry record. Without them, readers cannot determine the design’s operating characteristics or whether the planned decision process was completed.

The primary outcome is a proportion among evaluable subjects, so defining the denominator is central. The registry does not explain who qualifies as evaluable or how missing response assessments are handled. A response count without those rules could be difficult to interpret, and the record does not give the response count in any case.

The study’s single-group structure also limits the kinds of statistical conclusions it can support. A response rate can describe observed outcomes in the treated participants, but there is no concurrent comparator for estimating a treatment contrast. Randomization and masking are absent according to the registry. These design features do not invalidate a descriptive phase II question, but they constrain causal interpretation.

The record’s termination status and lack of reported analyses add uncertainty about study completion and outcome reporting. The reason for termination is not reported, and the registry provides no primary response estimate or secondary outcome analyses. The safety counts are useful as descriptions of events reported in the group, but do not establish attribution. Taken together, the information illustrates why a clear endpoint and design label are not substitutes for analysis results, prespecified analysis details, and an explicit account of missing data.

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.

Several limitations are specific to interpreting this trial from its registry record. The enrollment is recorded as 12, but the record does not say how many participants received pembrolizumab, completed treatment, or were evaluable for the primary endpoint. It also does not provide a participant flow account or explain exclusions from any analysis.

The primary outcome is defined by complete MRD response, but the assay, detection threshold, and operational response criteria are not reported in the registry record. The meaning of “evaluable subjects” is also not defined. These omissions prevent a reader from judging whether response classification was consistent or how the endpoint’s denominator was established.

The design description refers to a Simon two-stage optimum design but omits its stage sizes, response boundaries, stopping rules, and evidence that the stages were implemented as planned. The study’s own sample-size rationale is not reported in the registry record. The planning illustration described for the study uses two-arm equal allocation assumptions, which do not match the recorded single-group design, and should not be treated as the trial’s actual design or observed power.

The current status is terminated, but the reason and timing of termination are not reported. There is no reported primary efficacy result, no analysis of the secondary survival outcomes, and no statistical analysis output. Safety reporting gives group-level counts and one serious-event term, but not detailed timing, attribution, follow-up duration, or participant-level overlap among events and deaths.

Finally, the absence of a concurrent comparator limits causal interpretation even if descriptive outcomes were available. The registry record does not resolve whether the study reached its intended enrollment or completed planned follow-up. These limitations mean that the design and safety summaries can be described, but the efficacy question remains unanswered in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia — NCT02767934.
• Registry record last updated 2020-08-20; status last verified 2020-06.
• Results first posted 2020-08-11.
• 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

NCT02767934 is a phase II, single-group study sponsored by the University of Washington, titled “Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia.” The study record lists an enrollment of 12, a start date of 2017-01-13, a primary completion date of 2019-07-31, and a current status of terminated.

The treatment group received pembrolizumab, with cycles planned every 21 days for up to 2 years and possible additional treatment for participants achieving complete MRD response. The primary endpoint was the rate of complete MRD response among evaluable subjects over up to 2 years, with a Simon two-stage optimum design named in the record. Overall survival and relapse-free survival are listed as secondary outcomes.

No efficacy results or statistical analyses are reported in the registry record. The listed safety summary records 1 participant affected by a serious adverse event, 6 affected by other adverse events, and 5 deaths among a group with 12 participants at risk. The reason for termination and further analysis details are not reported in the registry record.