Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies (NCT01760655), a na phase 2 study. The primary outcome is Disease-free Survival (DFS).

2. Clinical Question

3. Trial Design

This is a phase II, single-group study of reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation. The registry lists enrollment of 62 and records the study as completed. Its start date is 2012-12-24, and its primary completion date is 2022-04-15. The registry does not report a randomized allocation or a masked design: allocation is listed as NA and masking as none.

The registered treatment plan combines conditioning with donor stem cell transplantation. The arm description says patients receive fludarabine phosphate on days -15 to -12, busulfan on days -14 to -13, donor lymphocyte infusion on day -6, total-body irradiation on day -10, and cyclophosphamide on days -3 and -2. Allogeneic peripheral blood stem cell transplantation is scheduled on day 0. Tacrolimus is listed as an intervention, but the arm-description text ends during its description of graft-versus-host disease prophylaxis; further protocol details are not reported in the registry record.

The conditions listed span multiple hematologic malignancies and related disorders. This breadth is important when interpreting an aggregate outcome: the registry record does not provide outcome results by diagnosis or other patient subgroup. It also does not report the eligibility details needed to determine how patients were selected within the listed conditions.

Secondary outcomes include overall survival, immune reconstitution at Day +28 and Day +90, graft-versus-host disease, and engraftment rates. Although the registry lists these outcomes, it does not report their results in the information available for this analysis. The absence of a control group means that the design can describe outcomes in the treated group but cannot isolate the regimen's effect from other influences through a randomized comparison.

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 Disease-free Survival (DFS), measured over 1 year post hematopoietic stem cell transplant (HSCT).

Disease-free survival (DFS) is the registered primary endpoint. It is specified as a proportion of participants and assessed at 1 year post hematopoietic stem cell transplant (HSCT). In general, DFS is a time-to-event outcome that reflects the time participants remain free of the events defined by the study's protocol. The precise event definition for this trial is not reported in the registry record, so it is not possible to say which events counted as a DFS failure.

The registry says the year DFS rate is to be estimated from Kaplan-Meier survival curves and reports a 95% confidence interval as the measure of uncertainty. In general, Kaplan-Meier estimation accounts for differing follow-up times and participants whose event status is not observed through the full follow-up period. A confidence interval conveys how precisely an estimate is supported by the observed data, subject to the method's assumptions.

The stated decision criterion is that the hypothesis would be rejected if the 95% confidence interval for the year DFS rate were entirely above 0.35. This is a criterion for interpreting an estimate, not an observed result. Neither the DFS estimate nor its confidence interval is reported in the registry record, and the event definition and analysis population are also not reported there.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry specifies Kaplan-Meier survival curves for estimating the primary year DFS rate and a 95% confidence interval for that estimate. It describes a criterion for rejecting the hypothesis: the interval must be entirely above 0.35. The registry does not report the estimated rate, interval limits, event definition, or detailed statistical analysis plan. Those omissions prevent an assessment of the actual primary analysis.

What does Kaplan-Meier estimation do?

In general, Kaplan-Meier estimation is used for time-to-event outcomes when participants may have different lengths of follow-up. It estimates the probability of remaining event-free over time while accounting for observations that are censored, such as participants whose event status is not known through the full follow-up period. Censoring is not itself an event. The method relies on assumptions, including that censoring is not informative in a way that systematically distorts the estimated event experience. The registry record does not report how censoring was handled or assessed in this trial.

A rate at a selected time point, such as the registered 1-year endpoint, is obtained from the estimated survival curve. The confidence interval expresses uncertainty around that estimate. In general, a narrower interval indicates greater precision and a wider interval indicates less precision; neither guarantees that the estimate is free from bias. The interval's interpretation also depends on the analysis method and its assumptions. Because no interval is reported, the precision of the DFS estimate cannot be evaluated.

How should the threshold criterion be read?

The registry's stated rule focuses on whether the whole 95% confidence interval is above 0.35. In general, this is more demanding than comparing only the point estimate with a threshold: the estimate must be sufficiently precise for the interval's lower end also to exceed the threshold. The registry record does not give the interval, so it is not possible to determine whether this condition was met. The criterion should not be mistaken for a reported finding or for proof of a treatment effect compared with a control group.

In general, a confidence interval is not a guarantee that the true value falls within its particular limits. It describes the uncertainty generated by a statistical procedure under its assumptions. For a single-group study, even a precisely estimated outcome remains an outcome observed in that group; it does not, by itself, estimate a causal contrast with another treatment.

What does the design imply for comparisons?

The study is registered as single-group, with allocation marked NA and masking listed as none. In general, random allocation helps make treatment groups comparable with respect to both measured and unmeasured factors. Without a concurrent randomized comparator, changes in patient mix, disease characteristics, supportive care, follow-up, and other influences cannot be separated from the treatment regimen using a simple comparison of outcomes. No adjusted comparative analysis is reported in the registry record.

The sample-size illustrations use assumptions described for planning: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. The stated illustrations are not the trial's own design justification and are not observed power. Their two-arm assumptions differ from this registered single-group design. In general, planning calculations depend on their assumptions and should not be interpreted as evidence that a study was adequately powered or that its result is reliable. The registry record does not report its own sample-size justification.

What can be inferred from the posted analyses?

The registry lists zero analyses in the available outcome information. In general, a registered endpoint or analysis rule is not a substitute for results. Without the endpoint estimate, confidence interval, event counts for the primary outcome, and analysis population, readers cannot reproduce or evaluate the primary analysis. The registry record also does not report interim analyses, a detailed statistical plan, or sensitivity analyses. Their presence or absence cannot be inferred from the listed endpoint definition.

The safety summaries use counts and percentages for events, which are binary summaries: whether a participant was recorded as having an event. In general, such summaries do not describe event timing, duration, recurrence, or the full distribution of severity unless those details are separately reported. These summaries answer a different question from the time-to-event primary endpoint and should not be treated as estimates of DFS.

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("Treatment (RIC and allogeneic PBSCT)")
n      <- c(62)
events <- c(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  Treatment (RIC and allogeneic PBSCT)  62  0  0.0  0.0  5.8  0.0  5.8  0.0  5.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including overall survival, immune reconstitution at Day +28 and Day +90, graft-versus-host disease, and engraftment rates. It does not report outcome analyses for these endpoints in the available results information. The registry record also does not report a multiplicity adjustment or a prespecified strategy for interpreting multiple outcomes.

In general, when many outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. Researchers may address this through prespecified hierarchies, adjusted significance thresholds, or by treating secondary results as exploratory. Which approach was used in this trial is not reported in the registry record. With no posted analyses, it is not possible to determine how multiplicity was handled in practice.

The record does not describe missing primary outcome data, censoring patterns, reasons for missingness, or sensitivity analyses. In general, missingness can affect an estimate if participants with unobserved outcomes differ systematically from those with observed outcomes. For a time-to-event endpoint, censoring methods account for incomplete follow-up under assumptions; they do not remove the need to understand follow-up completeness and the reasons observations end. Trial-specific details are not reported in the registry record.

The analysis population is also not described in the available results information. It is not reported whether the primary endpoint was analyzed among all enrolled participants, among those who received transplantation, or according to another definition. The registered enrollment figure alone does not establish who contributed to a particular analysis. These gaps limit assessment of the outcome denominators, the handling of exclusions, and the potential effects of missing data.

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: infection - grade 3 (6.5%), hypoxia - grade 3 (4.8%), acute kidney injury - grade 4 (3.2%), heart failure - grade 3 (3.2%), hypertension - grade 4 (3.2%).

The registry reports one treatment group, with 62 participants at risk for the serious adverse-event summary and 30 affected. For the other adverse-event summary, 62 were at risk and 43 were affected. These are counts of participants recorded as affected, not counts of all individual events; a participant may experience more than one event. The record lists serious adverse-event terms including Infection - grade 3 (6.5%), Hypoxia - grade 3 (4.8%), Acute Kidney Injury - Grade 4 (3.2%), Heart failure - grade 3 (3.2%), Hypertension - Grade 4 (3.2%), and Ileus - grade 3 (3.2%).

In general, adverse-event summaries depend on the registry's coding, reporting period, and definitions. The record does not provide enough detail to infer timing, duration, recurrence, or whether each listed term occurred in a different participant. Nor does it provide a control group for comparison. The counts and percentages describe reported events in this treatment group; they do not establish comparative safety or the cause of an event.

The registry also reports 27 deaths. The available information does not specify the causes or timing of these deaths, or how they relate to the primary DFS endpoint. These figures should be kept distinct from the unreported DFS estimate and interpreted only as the registry's adverse-event summaries.

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

The record describes a phase II study of reduced-intensity conditioning followed by donor stem cell transplantation in patients with high-risk hematologic malignancies. Its primary endpoint is disease-free survival at 1 year post HSCT, and its stated decision rule requires the 95% confidence interval to lie entirely above 0.35. This specifies the question and the intended statistical criterion, but the record does not report the DFS estimate or interval needed to answer that question.

The trial's single-group design means the registered outcomes, if reported, would characterize the treated group. They would not alone show how outcomes compare with another regimen or establish that the treatment caused an outcome. A randomized comparator is not registered, and the record does not report an adjusted comparative analysis.

The safety summaries report participants affected and selected serious adverse-event terms. They are relevant descriptions of reported events, but without comparative data and fuller event detail, they do not quantify how risks differ from those under another treatment. The death count is also reported without the detail needed to relate it to the primary endpoint.

In general, statistical evidence depends not only on a study question and analysis method but also on the results, their uncertainty, and the assumptions behind the analysis. For this trial, those primary efficacy results and several analysis details are not reported in the registry record. Consequently, the record supports a description of the study design and its registered aims, but not a conclusion that the primary endpoint threshold was reached, nor a conclusion about comparative efficacy.

The listed secondary outcomes likewise do not constitute findings in the absence of results. The registry record does not report their estimates or uncertainty. Conclusions about overall survival, immune reconstitution, graft-versus-host disease, or engraftment cannot be drawn from the endpoint names alone.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a study's prespecified question and the evidence needed to answer it. The record defines disease-free survival at 1 year as the primary endpoint, identifies Kaplan-Meier estimation, and states a confidence-interval threshold. These details describe an analysis framework. Without the resulting estimate and interval, however, readers cannot judge either the observed outcome or its precision.

The single-group design also illustrates the difference between estimating an outcome and estimating a treatment effect. In general, an outcome rate describes what was observed in a study population. A treatment effect requires a contrast with an appropriate alternative, and a randomized concurrent comparator helps protect that contrast from systematic differences between groups. This registry record has no such comparator.

The study's broad range of listed conditions makes population definition especially important for interpreting an aggregate result. The record does not report subgroup outcome analyses, so it cannot show whether outcomes differed across diagnoses. More generally, a pooled estimate can obscure variation in a heterogeneous population, and subgroup comparisons require their own methods and adequate information.

The safety summaries further demonstrate why counts, event terms, and comparative estimates answer different questions. Counts describe reported events within the treated group; they do not show whether the same events would be more or less common under another approach. The missing efficacy results and limited analysis details therefore matter as much as the registered endpoint definition when drawing statistical 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 principal limitation is that the registry record does not report the primary DFS estimate or its 95% confidence interval. It therefore does not allow assessment of the stated threshold criterion or the precision of the primary result. Although the study is marked completed, completion status does not itself provide outcome findings.

The record does not specify the DFS event definition, the analysis population, the handling of censoring, or the completeness of follow-up. These details affect how a time-to-event estimate should be interpreted. The posted information also does not report analyses for the listed secondary outcomes, nor does it give results by diagnosis or other subgroup.

The single-group design provides no randomized comparator for estimating a treatment contrast. Allocation is listed as NA and masking as none. This limits causal interpretation and prevents a like-for-like comparison within the registered design. The broad list of eligible conditions also means that an aggregate result, if available, might not describe each condition equally well; subgroup results are not reported.

Safety reporting is limited to participant counts, selected serious adverse-event terms and percentages, and a death count. The registry record does not provide event timing, causes of death, recurrence, or comparative safety estimates. The arm-description text is truncated during its graft-versus-host disease prophylaxis description, and protocol details beyond the listed interventions are not reported in the registry record.

The registry does not report the trial's sample-size justification, detailed statistical analysis plan, interim analyses, missing-data analyses, or approach to multiplicity. The planning illustrations are described as using assumptions that differ from the registered single-group design; they should not be treated as the trial's own design rationale or as observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies — NCT01760655.
• Registry record last updated 2025-10-30; status last verified 2025-10.
• Results first posted 2025-10-30.
• 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

NCT01760655 is a completed phase II, single-group study sponsored by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University. It enrolled 62 participants and investigated reduced-intensity conditioning before allogeneic peripheral blood stem cell transplantation for high-risk hematologic malignancies. The registered primary endpoint is disease-free survival at 1 year post HSCT, estimated using Kaplan-Meier curves, with a 95% confidence interval and a stated criterion involving 0.35.

The registry record does not report the primary DFS estimate or confidence interval, or results for the listed secondary outcomes. It reports adverse-event summaries for the treatment group, including 30 participants affected by serious adverse events, 43 affected by other adverse events, selected serious-event terms, and 27 deaths. The single-group design does not provide a randomized treatment comparison. Accordingly, the record supports description of the design and reported safety summaries, but not a conclusion about the primary endpoint result or comparative efficacy.