Lenalidomide and Ipilimumab After Stem Cell Transplant in Treating Patients With Hematologic or Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lenalidomide and Ipilimumab After Stem Cell Transplant in Treating Patients With Hematologic or Lymphoid Malignancies (NCT01919619), a na phase 2 study. The primary outcome is Number of Participants Experienced Severe Toxicity From Lenalidomide and Ipilimumab Post Transplant.

2. Clinical Question

The study also listed complete remission and progression-free survival as secondary outcomes. Their presence identifies other clinical questions of interest, but their results and analysis details are not reported in the registry record. The available information is therefore most useful for understanding the study design, its safety outcome definition, and the limits of the safety figures that are reported.

3. Trial Design

This was a phase 2 pilot study of lenalidomide alternating with ipilimumab after autologous or allogeneic stem cell transplantation. The registry record lists enrollment of 41 and the study status as completed. The start date is 2013-11-04, and the primary completion date is 2024-05-03. Those dates describe the registry record; they do not provide additional information about recruitment duration, follow-up completeness, or when individual participants completed treatment.

The design is recorded as single group, with allocation not applicable and no masking. Participants received the treatment regimen rather than being assigned to a separate control treatment. The safety data are organized by autologous and allogeneic transplant categories, but the registry record does not describe these as randomized groups. The categories should be understood as descriptive subgroups, not as a controlled comparison.

The intervention alternated lenalidomide and ipilimumab. Lenalidomide was taken orally once daily on days 1–21 of courses 1, 3, 5, and 7. One dose of ipilimumab was given intravenously over 90 minutes during courses 2, 4, 6, and 8, beginning 1–3 days after the last lenalidomide dose. Treatment was scheduled in courses every 28 days, for up to 8 courses. The registry description ends mid-sentence after a condition concerning absence of disease progression; additional regimen-stopping rules are not reported in the registry record.

The primary outcome was a participant count for severe toxicity up to 30 days following the last dose of study drugs. Complete remission and progression-free survival were listed as secondary outcomes. The registry record lists 3 outcome measures and 0 analyses. It does not report the results for the primary endpoint or the listed secondary outcomes, nor does it describe the statistical analysis plan, analysis populations, or handling of incomplete outcome data. Accordingly, the design and intended outcomes can be characterized, but efficacy conclusions or a complete quantitative assessment of primary safety cannot be drawn from the reported 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

Reasons for not completing this period:

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 Number of Participants Experienced Severe Toxicity From Lenalidomide and Ipilimumab Post Transplant, measured over Up to 30 days following the last dose of study drugs.

The primary endpoint counts participants who experienced severe toxicity from lenalidomide and ipilimumab after transplantation. Its definition includes any grade 4 hematological toxicity or grade 3–5 organ toxicity. The assessment window is up to 30 days following the last dose of study drugs. The endpoint is expressed in participants, rather than as a continuous measurement or a time-to-event summary.

A participant count is a direct way to describe how many people met a prespecified safety definition in the recorded observation period. It can make a clinically important safety question easy to state. However, a count alone does not describe the range or duration of events, their timing, or whether participants experienced more than one event. The endpoint definition combines hematological and organ toxicities, so the count also does not by itself show which kinds of toxicity contributed.

For interpretation, the count needs its analysis denominator and clear information about follow-up and ascertainment. The registry record gives the endpoint definition and timeframe, but it does not report the observed primary-endpoint count, a confidence interval, or a statistical analysis. It therefore does not establish the frequency or precision of this primary outcome. The serious adverse event figures reported separately are not a substitute for this endpoint: the registry record does not state that the serious-event categories use the same toxicity grades, outcome definition, or assessment window.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on separating the study question, the outcome definition, the observed data, and the analysis used to summarize those data. The registry record describes the first two for the primary safety endpoint, but does not report the endpoint result or an analysis. General statistical concepts can clarify what the missing information would ordinarily contribute without filling in the unreported result.

What does a participant count represent?

A count endpoint records how many participants meet a specified event definition during a stated observation period. Here, the definition concerns grade 4 hematological toxicity or grade 3–5 organ toxicity, and the stated period extends up to 30 days following the last dose of study drugs. A count is not the same as the number of individual adverse events: one participant may have more than one event, while a participant-based endpoint counts that participant according to whether the definition was met.

To interpret a count as a frequency, the relevant denominator also matters. It should be clear which participants were eligible for the endpoint assessment and whether all had adequate follow-up. The registry record does not report the primary endpoint count or its denominator. The at-risk and affected counts in the separately reported adverse-event groups cannot be substituted for a missing denominator for the primary endpoint, because the record does not say that these are the same outcome or analysis population.

What would an interval estimate add?

General: a confidence interval expresses the statistical uncertainty around an estimate under a specified method and its assumptions. For a participant-count outcome, an interval around a proportion can help show that a result is not known with perfect precision, particularly when the number of observations is limited. An interval does not resolve problems such as incomplete follow-up, selection, or lack of a control group. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed from the available result information.

Why does the single-group design matter?

The study is recorded as single group, with allocation not applicable and masking none. General: a control group can help distinguish changes associated with an intervention from changes that could occur over time, arise from the underlying condition, or reflect other care. Without a control group, observed events during treatment can be described, but their cause cannot be established by the study design alone. The autologous and allogeneic categories do not supply that control: both are described as receiving lenalidomide and ipilimumab, and the registry does not identify them as randomized groups.

Comparisons between nonrandomized subgroups can also reflect differences in who enters each group or in their clinical circumstances. The registry record does not report adjusted analyses or other methods intended to address such differences. Therefore, the subgroup safety entries should be read as descriptions, not as estimates of a treatment effect or evidence that one transplant category has a better safety outcome.

How should adverse-event summaries be read?

The record reports affected participants and participants at risk for serious and other adverse events within each transplant category. General: the denominator gives context for a count, but the definition of an event, the observation window, completeness of reporting, and rules for counting participants all matter. A list of event terms can describe what was recorded, but it does not by itself explain severity, duration, recurrence, or causality. The registry record lists low granulocyte, low platelet, and viral among the top serious terms, with percentages, but does not report additional context sufficient to connect those entries to the primary endpoint.

For causal interpretation, it is important to know how investigators judged whether an event was related to study treatment, when it began, and how events were collected. Those details are not reported in the registry record as part of the registry entries available for this study. The event figures should therefore be understood as reported safety summaries, not causal estimates.

What can planning calculations say?

General: sample-size planning illustrations describe hypothetical designs under stated assumptions; they are not observed results and do not indicate the precision actually achieved in a completed study. The planning assumptions described for this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a fraction of the observed effect. The registry record identifies the study itself as single group, so those planning assumptions do not change its design into a randomized comparison. The planning illustration is not the trial’s own design, and its assumed two-arm allocation should not be confused with the autologous and allogeneic safety categories.

General: statistical power is a feature of a proposed design under specified assumptions, not a measure of whether a completed study found a clinically important result. A planning illustration based on an observed effect also depends on that effect estimate, which can be uncertain. No planning result is a substitute for the primary endpoint data, a confidence interval, or the analysis plan. No numerical planning result is reported in the registry record, and no sample-size justification for the actual trial is reported.

What is not documented?

The registry record lists 0 analyses and does not provide a statistical analysis plan, an adjustment strategy, or analysis populations. It does not report how missing outcomes were handled, whether all enrolled participants were included in each outcome summary, or whether any interim analysis was planned or conducted. General: these details help determine what a reported estimate represents and how robustly it can be interpreted. Their absence means that no unreported method should be assumed. The sponsor's own analysis takes precedence if the record reports a discrepancy between sponsor analysis and a recalculation; no such recalculated result or discrepancy is reported in the registry record for this study.

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("Autologous -Treatment (Lenalidomide and Ipilimumab", "Allogeneic - Treatment (Lenalidomide and Ipilimuma")
n      <- c(28, 13)
events <- c(10, 2)
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  Autologous -Treatment (Lenalidomide and Ipilimumab  28  10  35.7  18.6  55.9  20.7  54.2  20.7  54.3
ARM  Allogeneic - Treatment (Lenalidomide and Ipilimuma  13  2  15.4  1.9  45.4  4.3  42.2  4.7  42.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures: the primary severe-toxicity count and the secondary outcomes of complete remission and progression-free survival. It lists 0 analyses. No statistical analysis plan, hierarchy among secondary outcomes, or method for accounting for multiple outcome tests is reported in the registry record.

General: when several outcomes are assessed, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate plan. A prespecified hierarchy or multiplicity adjustment can help define how confirmatory claims are made. That general issue does not establish that this study used, or should have used, any particular procedure. No adjustment should be inferred when none is reported.

The primary endpoint is defined, but its observed count and analysis are not reported. Results for complete remission and progression-free survival are also not reported. Therefore, multiplicity cannot be evaluated from reported statistical results, and no conclusion about the presence or absence of statistically significant findings is warranted.

Missing-data handling and analysis populations are not reported in the registry record. It does not state whether all enrolled participants contributed to each outcome, how incomplete follow-up was treated, or whether exclusions occurred. These matters are important because an outcome count depends on who was assessed and over what period. No assumptions about missingness or the population analyzed should be added to the 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: low granulocyte (35.7%), low platelet (7.7%), viral (7.7%).

The registry record reports serious and other adverse-event counts separately for autologous and allogeneic treatment groups. In the autologous group, 10 participants were affected by serious adverse events among 28 at risk, and 25 were affected by other adverse events among 28 at risk; 7 deaths are also listed. In the allogeneic group, 2 participants were affected by serious adverse events among 13 at risk, and 13 were affected by other adverse events among 13 at risk; 5 deaths are listed. These entries are descriptive safety summaries, not results of a randomized comparison.

The top serious adverse event terms include low granulocyte at 35.7%, low platelet at 7.7%, and viral at 7.7%. The record does not state enough about these percentages to treat them as rates for the primary endpoint or to infer their relationship to the group-level affected-participant counts. It also does not report event timing, duration, recurrence, or treatment attribution in these summaries.

The deaths are not identified by cause, timing, or relationship to study treatment. Their listing alone does not establish that treatment caused them. The serious adverse event summaries also should not be substituted for the primary toxicity endpoint, which has a separate grade-based definition and assessment window. The observed primary-endpoint result is not reported in the registry record.

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

The record establishes that a phase 2 pilot study evaluated alternating lenalidomide and ipilimumab after stem cell transplantation, with severe toxicity as its primary outcome. It also provides some safety counts and lists complete remission and progression-free survival as secondary outcomes. These details describe what the study set out to examine and the safety information entered in the registry.

The primary endpoint result is not reported. Consequently, the record does not establish how many participants met the endpoint definition, how frequently the defined toxicity occurred, or how precisely that frequency was estimated. The separate adverse-event data offer descriptive counts for the autologous and allogeneic treatment categories, but they do not answer the primary endpoint unless their definitions and observation windows are shown to match, which the registry record does not establish.

The single-group design also limits interpretation. There is no separate control group in the registry record, and the transplant categories are not described as randomized comparisons. Thus, the available information cannot isolate the effects of the study treatment from other possible explanations for events observed during follow-up. The safety summaries should not be used to conclude that the regimen caused or prevented a particular event.

The registry record does not report results for the secondary outcomes, a statistical analysis plan, analysis populations, or handling of missing data. It therefore cannot support conclusions about complete remission or progression-free survival, nor does it permit a full assessment of how the outcomes were analyzed. This does not mean that the study had no findings; it means the findings and analysis details are not reported in the registry record.

The appropriate interpretation is bounded: the record documents a completed pilot study and its intended safety question, along with selected adverse-event summaries. It does not provide the primary outcome result or the information needed for comparative effectiveness claims. Statistical description of the reported counts should remain distinct from a causal or treatment-benefit conclusion.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly defined endpoint and a reported endpoint result. The registry record specifies a severe-toxicity definition and an assessment window, yet does not report the primary outcome count or its analysis. A well-described outcome question is necessary for interpretation, but it cannot by itself show what was observed or how uncertain an estimate may be.

The design also illustrates why descriptive subgroups should not be mistaken for treatment comparisons. The safety data distinguish autologous and allogeneic transplant categories, but both are treatment groups within a single-group study. Without a separately assigned control group, differences between these categories would not isolate the effect of lenalidomide and ipilimumab. Their counts remain useful as descriptions of what the registry records, subject to the limitations in event definitions and follow-up details.

Safety interpretation depends on more than event counts. The primary outcome combines specified grades of hematological and organ toxicity, while the separately reported adverse-event summaries use serious and other event categories. The record does not establish that these measures are interchangeable. Keeping endpoint definitions distinct prevents a descriptive safety entry from being treated as the missing primary result.

Finally, the absence of a reported analysis plan, analysis populations, and missing-data methods limits assessment of how the results were intended to be interpreted. These are not minor details when determining the denominator, uncertainty, and scope of an estimate. The record supports a careful account of the study’s design and reported safety summaries, while also making clear where outcome and analysis information is not reported.

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 endpoint result is not reported in the registry record. Although its definition and timeframe are specified, the observed count, denominator, and uncertainty estimate are absent. This prevents a quantitative assessment of the main safety question.

The study is recorded as single group, with no masking and allocation listed as not applicable. There is no separate control group described. The autologous and allogeneic categories are both treatment groups, so their reported safety entries do not provide a randomized comparison. The record does not describe adjusted analyses that might address differences between these categories.

The serious and other adverse-event counts are reported, but event definitions, timing, duration, recurrence, and treatment attribution are not posted in these summaries. The listed serious-event terms and percentages are not enough to determine how they relate to the primary grade-based endpoint. The deaths are listed without causes or relationship to treatment.

The registry record does not report the statistical analysis plan, analysis populations, handling of missing data, or results for the listed secondary outcomes. It also does not report whether interim analyses occurred. These gaps limit assessment of outcome completeness, analytical choices, and the precision or robustness of results. The regimen description is cut off after its condition concerning disease progression, so further treatment rules are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lenalidomide and Ipilimumab After Stem Cell Transplant in Treating Patients With Hematologic or Lymphoid Malignancies — NCT01919619.
• Registry record last updated 2024-12-03; status last verified 2024-11.
• Results first posted 2024-12-03.
• 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

The registry record describes a completed phase 2 pilot study of lenalidomide alternating with ipilimumab after autologous or allogeneic stem cell transplantation for hematologic or lymphoid malignancies. Enrollment is listed as 41. The study is single group, with allocation not applicable and no masking.

The primary outcome was the number of participants experiencing severe toxicity, defined as any grade 4 hematological toxicity or grade 3–5 organ toxicity up to 30 days following the last dose of study drugs. The record lists complete remission and progression-free survival as secondary outcomes. It reports 0 analyses, and the observed primary and secondary outcome results are not reported in the registry record.

Safety summaries are reported separately for autologous and allogeneic treatment groups, including serious and other adverse events and deaths. These are descriptive entries, not a controlled treatment comparison. The statistical analysis plan, analysis populations, and missing-data methods are not reported.