Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation (NCT02259348), a na phase 2 study. The primary outcome is Percentage of Participants Engrafted by Day 42 Post-transplant.

2. Clinical Question

3. Trial Design

The registry describes a phase II, single-group study of a transplant regimen for younger patients with hematologic malignancies relapsed or refractory after a prior transplant. Enrollment is listed as 12. The study began in 2014-10, had primary completion in 2015-04, and is recorded as terminated. These registry entries describe the study record; they do not establish how many participants received each component or completed follow-up.

The intervention combines reduced intensity conditioning with haploidentical natural killer cell therapy followed by transplantation of T-cell-depleted progenitor cells. The participant arm description lists cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan, followed by transplant procedures. Other listed interventions include G-CSF. The registry describes the transplant sequence and the rationale in broad terms, but does not report detailed administration schedules in the information available.

There is no randomized allocation and no concurrent control arm described. Thus, the study is not structured to estimate a treatment effect relative to another regimen. Its primary objective is to estimate engraftment by Day 42 under the study approach. Secondary outcomes listed in the record include malignant relapse, event-free survival, overall survival, acute and chronic graft-versus-host disease, and transplant-related mortality. Their listing does not mean that results for those outcomes are reported.

The record lists 9 outcome measures and 0 analyses. It does not report the protocol’s sample-size justification, statistical analysis plan, interim analyses, or detailed analysis populations. The registry status is terminated, but the reason for termination is not reported in the registry record. These omissions limit what can be inferred about study conduct and the intended statistical interpretation.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Six enrolled participants were blood donors and did not undergo transplantation.

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 Percentage of Participants Engrafted by Day 42 Post-transplant, measured over Day 42 post transplantation.

The primary endpoint is the percentage of participants who achieve engraftment by Day 42 post-transplant. The registry defines engraftment as the first of 3 consecutive tests performed on different days with an ANC ≥ 500/mm^3 and evidence of donor cell engraftment. The endpoint therefore combines a blood-count threshold, confirmation across consecutive testing days, and evidence that the cells are donor-derived.

In general, an endpoint definition makes an outcome measurable in a consistent way. A specified assessment window also establishes when the outcome is being evaluated. Engraftment is used in this study as an early transplant outcome: it records whether the defined blood-count and donor-engraftment criteria have been met by the stated time point. It is not, by itself, a measure of longer-term survival, relapse, or freedom from transplant complications.

The registry record does not report the number meeting the definition, the denominator assessed, the estimated percentage, or a confidence interval. It also does not describe how missing or unevaluable Day 42 assessments would be handled. Without those details, the endpoint’s observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods turn clinical observations into estimates that can be interpreted consistently. For this study, the central planned estimate is a percentage: the proportion of assessed participants who meet the registry’s engraftment definition by Day 42. The record states the endpoint definition, but does not report an estimate, its uncertainty, or a method for calculating it.

What does a percentage estimate describe?

In general, a percentage for a binary outcome summarizes the share of an analysis group classified as having the event. Its meaning depends on both the event definition and the denominator. Here, the event is meeting the specified engraftment criteria by the stated time point. The registry lists enrollment as 12, but does not report the endpoint denominator. Enrollment alone cannot establish how many participants were assessed or included in an analysis.

In general, a confidence interval expresses uncertainty around an estimate. It reflects the fact that results from a limited study group may not precisely identify the corresponding rate in a broader population. A confidence interval would be needed to assess the precision of an observed engraftment percentage; none is reported in the registry record. It would not remove the limitations of a single-group design or account automatically for missing assessments or differences between participants.

Why does the study design matter?

In general, random allocation to a concurrent control group can help make groups comparable for estimating a treatment contrast. This trial is recorded as single-group, with allocation listed as not applicable. There is therefore no randomized comparison on which to base a relative effect estimate. A single-group event rate can be descriptive, but it cannot distinguish the influence of the study regimen from other factors that may affect the outcome.

The record also does not report a statistical analysis plan, sample-size justification, interim analyses, or details of any adjustment strategy. Those details matter because they describe how outcomes were to be analyzed, how uncertainty was to be quantified, and whether repeated looks or multiple outcomes influenced interpretation. Their absence from the registry record does not establish what was or was not done outside the record.

How should the sample-size illustrations be read?

In general, sample-size calculations describe planning under stated assumptions; they are not observed clinical results. The planning assumptions associated with this study describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. They are explicitly planning illustrations, not the trial’s own design. Because the actual study is single-group, the equal-allocation comparison assumptions do not describe its recorded design.

The illustrations are not observed power and do not show that a planned analysis was conducted. The registry record does not report a trial-specific sample-size justification or the observed effect needed to interpret such an illustration. The assumptions also cannot substitute for a reported endpoint estimate and its confidence interval. Any sample-size values associated with these assumptions should be understood as hypothetical planning quantities, not evidence about the trial’s outcome.

What do the safety summaries contribute?

In general, adverse event summaries describe the events recorded and the number of participants affected within a defined observation context. Serious adverse events and other adverse events are separate summaries. A list of selected serious-event terms can signal which event categories appear in the record, but percentages alone do not explain timing, duration, severity beyond the serious classification, attribution, or recurrence. The registry record gives limited context for these figures, so they should not be treated as comparative risk estimates.

More broadly, statistical interpretation depends on knowing who was included, what was measured, when it was assessed, and how missing values were handled. The endpoint definition offers a clear classification rule, but the record does not report the primary outcome data or key analysis details. That makes it impossible to evaluate the empirical estimate, its precision, or the sensitivity of findings to analysis choices.

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("Participants")
n      <- c(6)
events <- c(6)
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  Participants  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary engraftment endpoint and secondary outcomes related to relapse, survival, graft-versus-host disease, and transplant-related mortality. It reports 0 analyses. No multiplicity strategy is reported in the registry record. In general, testing many outcomes can increase the chance of finding an apparently notable result by chance, so an analysis plan may specify which outcomes are primary and how secondary findings will be interpreted. The registry identifies a primary endpoint, but does not provide enough information to establish how multiplicity was handled.

Missing-data handling is also not reported in the registry record. The entry defines the Day 42 engraftment criteria but does not state how participants without an assessment, with incomplete testing, or with an unevaluable result would be classified. These choices can affect the numerator and denominator of a percentage estimate. The record does not report the denominator used, missingness frequency, or any sensitivity analysis.

The analysis populations are not described. It is therefore not reported in the registry record whether the intended endpoint analysis included all enrolled participants, only those receiving the transplant, or another defined group. The listed enrollment of 12 should not be treated as the analysis denominator without that information.

These are reporting gaps, not evidence that particular methods were or were not used. The registry record does not report a statistical analysis plan, adjustment methods, or interim analyses. Without those details and the outcome data, the completeness and robustness of any analysis cannot be evaluated.

12. Safety Results

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

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: seizure (33.3%), respiratory failure (disorder) (33.3%), hemorrhage, pulmonary (16.7%), hepatic failure (disorder) (16.7%), infection, candida glabrata, gi tract (16.7%).

The registry lists serious adverse event figures for the Participants group: 6 were at risk and 5 were affected. For other adverse events, 6 were at risk and 6 were affected. These are separate registry summaries; they should not be combined into a new total. The record does not report deaths in these group fields.

Selected serious adverse event terms include seizure and respiratory failure (disorder), each listed as 33.3%. Hemorrhage, pulmonary; hepatic failure (disorder); infection, candida glabrata, GI tract; and infection, culture negative, sepsis are each listed as 16.7%. These percentages describe the registry’s reported terms, not comparative risks against another treatment. The record does not provide the event-specific denominators, timing, duration, or attribution details needed for a fuller interpretation.

In general, serious adverse event summaries identify events meeting a seriousness classification; they do not alone establish that treatment caused an event. The single-group design has no concurrent control group for a relative safety comparison, and the registry figures should be read descriptively. The limited reported context also means the percentages should not be used to infer whether events were recurrent, mutually exclusive, or experienced by the same participant.

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

The registry record describes a phase II single-group transplant study and defines a primary endpoint: the percentage of participants meeting the engraftment criteria by Day 42. It also lists enrollment as 12, the study status as terminated, and several secondary outcomes. These details help identify the clinical question and the scope of intended observation.

The record does not report the primary endpoint result. It gives no observed percentage, numerator, analysis denominator, or confidence interval. Consequently, it is not possible to state what proportion achieved engraftment or how precisely that proportion was estimated. The absence of reported results also prevents assessment of the listed secondary outcomes.

Even with an outcome estimate, the single-group design would support a descriptive account of participants’ experience rather than a randomized comparison with another approach. There is no concurrent control group in the registry record, so a treatment contrast cannot be estimated from this study structure alone. The record also does not report enough information about participant flow, analysis populations, or missing data to determine how an endpoint estimate would apply to everyone enrolled.

The serious adverse event figures provide descriptive safety information, but they do not establish causation or comparative safety. The registry does not report the timing and attribution details needed to interpret these events in depth.

Accordingly, the study’s stated endpoint and design can be described, but the clinical outcome cannot be judged from the registry record. No conclusion about the regimen’s benefit or lack of benefit follows from an endpoint whose observed result is not reported. The record also does not report the reason for termination, so that status should not be interpreted as evidence about the regimen’s effects.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The registry specifies a Day 42 engraftment criterion that combines an ANC threshold, consecutive testing, and evidence of donor cell engraftment. That definition identifies what would count as the event, but without the observed numerator, denominator, and uncertainty, the endpoint cannot be evaluated empirically.

The single-group structure is another important statistical feature. It can describe outcomes in participants treated under a particular approach, but it does not create a randomized comparison. This distinction matters because an event rate and a treatment effect are different quantities: the former describes outcomes in a group, while the latter requires a meaningful comparator and a contrast between groups or strategies.

The record also makes clear that listed outcomes are not equivalent to reported findings. Relapse, survival, graft-versus-host disease, and transplant-related mortality are identified as secondary outcomes, yet the record lists 0 analyses. A reader needs actual estimates and methods to assess those outcomes, along with information about follow-up and analysis populations.

Finally, the serious adverse event figures show why denominators and context matter. Percentages can be difficult to interpret without details about event definitions, observation periods, attribution, and whether events overlap. This record offers a limited descriptive safety summary rather than a controlled comparison. Taken together, the study is statistically informative as an example of how design and reporting determine what conclusions are supportable, even when the clinical question is clearly stated.

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 principal limitation for interpretation is that the registry record does not report the primary endpoint result. Although engraftment is defined by Day 42, no observed percentage, numerator, denominator, or confidence interval is available. The record therefore does not permit assessment of the frequency or precision of this outcome.

The study is recorded as single-group with allocation not applicable. There is no randomized comparator in the record, limiting interpretation to descriptive outcomes rather than a controlled estimate of relative effect. The record also does not report detailed participant characteristics, the number receiving the transplant, or the number with an evaluable Day 42 assessment. Enrollment is listed as 12, but the analysis population is not specified.

The study is marked terminated, while the reason for termination is not reported in the registry record. The listed start and primary completion dates do not establish the duration of follow-up for each participant. Follow-up details, missing-data methods, analysis plans, and interim analyses are also not reported. The record lists 9 outcome measures and 0 analyses, leaving no reported estimates for the primary or secondary outcomes.

Safety interpretation is constrained by limited context around the reported serious adverse event summaries. The registry does not report event timing, attribution, or enough detail to establish how the percentages relate to the full observation period. These figures cannot support a comparative safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation — NCT02259348.
• Registry record last updated 2017-05-30; status last verified 2016-09.
• Results first posted 2016-05-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a phase II, single-group study of a haploidentical transplant approach for younger patients with hematologic malignancies relapsed or refractory after a prior transplant. Enrollment is listed as 12; the study is marked terminated. Its primary endpoint is the percentage meeting a defined engraftment criterion by Day 42 post-transplant.

The record lists secondary outcomes covering relapse, survival, graft-versus-host disease, and transplant-related mortality. It reports 0 analyses and does not give the primary endpoint result, analysis denominator, or confidence interval. There is no concurrent randomized control group. Serious adverse event summaries are listed, but with limited interpretive context. The reason for termination, missing-data approach, analysis populations, and statistical analysis plan are not reported in the registry record.