Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation (NCT02458235), a na phase 2 study. The primary outcome is Relapse Rate.

2. Clinical Question

The clinical question is therefore about relapse and safety after a combined post-transplant strategy in the enrolled group, rather than about a treatment difference between groups. The registry description identifies several diseases and a pediatric and young adult target population, but the enrolled participants’ disease-specific characteristics and age distribution are not reported in the registry record. Likewise, the number of participants in each risk category is not reported in the registry record. Without those details or a concurrent comparator, the registry information cannot establish how relapse outcomes differed by disease, risk group, or another treatment strategy.

3. Trial Design

This was a phase II, completed, single-group study sponsored by the University of California, San Francisco. The registry lists an enrollment of 17 and describes azacitidine with donor lymphocyte infusion as the intervention. Allocation is listed as not applicable, consistent with the absence of a randomized comparison. Masking is listed as none.

The intended approach was risk-adapted. The registry description says participants would be stratified into low-, standard-, and high-risk categories using graft-versus-host disease status, mixed versus full donor chimerism, and positive versus negative minimal residual disease results. The description refers to up to 7 cycles of low-dose azacitidine. Further regimen details and the actual treatment received by participants are not reported in the registry record.

The primary outcome was relapse rate, defined as the percentage of participants who relapsed, with a timeframe of up to 2 years. Secondary outcomes listed were median relapse-free survival and median time to relapse. The registry lists 8 outcome measures, but numerical results for relapse rate and the secondary outcomes are not reported in the registry record.

The study started on 2015-06-02, reached primary completion on 2019-03-15, and is listed as completed. Completion status does not itself indicate that each outcome result was posted. The record does not report a concurrent control arm, a randomized allocation process, or a masking procedure. The sample-size justification and detailed statistical plan 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 Relapse Rate, measured over Up to 2 years.

The primary endpoint is relapse rate, expressed as the percentage of participants who relapsed up to 2 years after the post-transplant intervention. This is a binary outcome at the participant level: each participant is classified according to whether a relapse occurred within the stated follow-up period. The endpoint is used to describe how often relapse occurred in the enrolled group over the specified timeframe.

The registry description states that pediatric acute leukemia relapse after transplant was assumed to be 40%, and that azacitidine with or without donor lymphocyte infusion was expected to reduce the 2-year relapse rate by approximately 40% to a rate of 25%. These are statements of assumptions and expectations in the outcome description, not observed results from this study. The numerical relapse rate observed among the 17 participants is not reported in the registry record.

A percentage is straightforward to interpret, but its precision depends on the number of participants and the number with the event. A confidence interval would describe uncertainty around an estimated percentage; no confidence interval for the primary endpoint is reported in the registry record. Because the study has one group and no concurrent comparator, its relapse rate would describe that group, not by itself the effect attributable to the combined intervention.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group study with a binary primary outcome. The basic descriptive quantity for such an outcome is the proportion of participants who experienced relapse during the stated timeframe. The endpoint description calls this a percentage of participants. No observed percentage is reported in the registry record, so there is no estimate to interpret or compare with the assumptions in the description.

What does a confidence interval tell the reader?

As a general statistical concept, a confidence interval represents uncertainty around an estimate. For a proportion, it conveys how compatible a range of underlying event rates is with the observed data under the method’s assumptions. An interval is not a guarantee that the true rate lies within its bounds, and it does not replace the estimate itself. The registry record does not report a confidence interval for relapse rate, so the precision of the primary endpoint cannot be assessed from the posted information.

Why does the single-group design matter?

As a general design principle, a single-group study can describe outcomes among participants who received the intervention, but it cannot directly estimate a between-group treatment contrast. A comparison with an external expectation or historical rate is not equivalent to a randomized control group: differences in participant characteristics, care, outcome definitions, and follow-up may influence results. In this study, no concurrent comparator is listed. The relapse-rate assumptions in the endpoint description therefore provide context for the planned question, not a control outcome observed during the study.

The intervention is described as risk-adapted, with categories based on graft-versus-host disease status, donor chimerism, and minimal residual disease. Stratification can organize treatment decisions or analyses around characteristics expected to distinguish participants. The registry record does not report how many participants were in each category, whether the intended categories were applied as described, or whether outcomes were analyzed by category. Such details should not be inferred from the description alone.

How should the planning assumptions be read?

The endpoint description states an assumed relapse rate of 40% after transplant for pediatric acute leukemia and an expected reduction of approximately 40% to a rate of 25%. These values are part of the study’s stated expectations, not observed findings. The rationale for the enrollment of 17 and a formal sample-size justification are not reported in the registry record. Any sample-size illustrations associated with this analysis are planning scenarios, not observed power. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a hypothetical two-arm calculation, whereas this trial is listed as single-group; they should not be mistaken for the design or analysis actually used in this study.

As a general statistical concept, power is a design-stage probability tied to a specified effect, sample size, analysis method, and error threshold. It is not a measure of whether a completed study succeeded. A planning illustration based on a fraction of an observed effect is not evidence that the study had that power, and no observed-effect estimate is reported in the registry record for evaluating such an illustration.

What can safety counts establish?

Adverse-event counts provide a descriptive account of events reported among participants. They do not by themselves establish that the intervention caused an event. The serious-event data list 17 participants at risk and 10 affected; the other-event data list 17 at risk and 17 affected. The record gives no comparative safety group. As a general principle, event categories may overlap within participants, and the same participant can experience multiple events. Therefore, category-level percentages should not be added to obtain a total number of affected participants.

The registry lists median relapse-free survival and median time to relapse as secondary outcomes, but does not post their numerical results. Time-to-event methods generally account for the timing of events and may also need to handle participants whose event status is unknown at the end of follow-up. The exact methods used, censoring rules, and analysis populations are not reported in the registry record. No particular estimator, model, or adjustment should be attributed to the study without that information.

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("Azacitidine/Donor Lymphocyte Infusion")
n      <- c(17)
events <- c(4)
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  Azacitidine/Donor Lymphocyte Infusion  17  4  23.5  6.8  49.9  9.6  47.3  9.7  47.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including relapse rate, median relapse-free survival, and median time to relapse. When a study evaluates multiple outcomes or multiple analyses, multiplicity can affect how statistical evidence is interpreted. As a general concept, testing many hypotheses can increase the chance of at least one apparently unusual result. A prespecified strategy may address this issue, but the multiplicity approach is not reported in the registry record. The registry lists 0 analyses, and no statistical analysis plan or outcome analysis results are reported.

Information about missing outcome data, follow-up completeness, and how missing measurements were handled is not reported in the registry record. The record also does not describe the analysis populations, such as whether all enrolled participants were included in each outcome analysis or whether eligibility for an analysis depended on treatment received or follow-up. These details matter because exclusions or incomplete follow-up can change the group represented by an estimate.

The registry record does not report whether any interim analyses occurred, what rules governed them, or whether the listed outcomes were analyzed according to a prespecified hierarchy. Those details should not be inferred from the study’s phase or completion status. Without the outcome estimates, missing-data information, analysis populations, and multiplicity plan, the posted record does not permit a full assessment of the statistical evidence for the primary or secondary outcomes.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: immune system disorders - other (17.6%), rash maculo-papular (5.9%), fever (5.9%), infections and infestations - other (5.9%), musculoskeletal and connective tissue disorder - other (5.9%).

The adverse-event record lists 17 participants at risk for serious adverse events and 10 affected. For other adverse events, it lists 17 at risk and 17 affected. Deaths are listed as 0. These are descriptive counts for the single intervention group; there is no concurrent comparison group in the study design.

The listed serious adverse event terms include immune system disorders - other at 17.6%, rash maculo-papular at 5.9%, fever at 5.9%, infections and infestations - other at 5.9%, musculoskeletal and connective tissue disorder - other at 5.9%, and edema face at 5.9%. These terms and percentages describe entries in the registry safety record. They do not show whether an event was caused by the intervention, how severe it was beyond its serious-event classification, or how long it lasted.

As a general statistical caution, participants can experience more than one event or appear under more than one event term. The listed percentages should not be summed or interpreted as distinct participant totals. The counts also cannot establish a comparative safety difference without a control group and more detailed context. The registry record does not report further event-level details such as timing, treatment relationship, or outcome.

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

The registry record describes a phase II investigation of azacitidine with donor lymphocyte infusion after allogeneic stem cell transplantation, with relapse rate as the primary endpoint. It also provides descriptive safety counts for the single intervention group. These registry entries identify the clinical question and the kinds of outcomes the study was intended to assess.

The numerical primary relapse-rate result is not reported in the registry record. The stated expectation of a rate of 25%, and the assumed rate of 40%, are not observed results. The posted information therefore does not establish the relapse rate among participants or how precisely it was estimated. It also does not report numerical results for the listed secondary outcomes of median relapse-free survival and median time to relapse.

Even if a single-group relapse rate were available, it would describe outcomes in the enrolled participants rather than directly measure a causal treatment effect. A concurrent comparator would be needed for a direct comparison under the same study conditions. Without one, differences from a historical expectation could reflect participant mix, transplant and disease factors, follow-up, or other influences as well as treatment.

The safety counts show that serious and other adverse events were reported among participants, with deaths listed as 0. They do not establish that the intervention caused or prevented those events, and there is no control group for estimating a comparative safety difference. The event terms and percentages should be read as descriptive registry entries rather than as a complete account of the clinical context.

Accordingly, the registry record supports a description of the design, intended endpoints, and posted adverse-event figures, but not a conclusion about whether the intervention reduced relapse or changed safety relative to another approach. Missing outcome estimates and details about analysis methods, missing data, and analysis populations limit further interpretation.

14. Why This Trial Matters Statistically

This study raises a clinically focused statistical question: how to describe relapse and safety after a risk-adapted post-transplant strategy in pediatric and young adult patients with hematologic malignancies. The registry’s single-group design is important because it distinguishes estimation of outcomes in one treated group from estimation of a treatment effect. Those are different statistical questions, even when the clinical aim concerns prevention.

The planned use of risk categories also highlights the role of participant characteristics in interpreting outcomes. Graft-versus-host disease status, donor chimerism, and minimal residual disease were named as factors defining risk categories. These characteristics may be relevant to how outcomes are summarized, but the registry record does not report category sizes or category-specific results. Without them, readers cannot assess whether the observed group would represent a particular risk profile even if the primary result were posted.

The record also illustrates why a completed study designation and a stated endpoint do not substitute for outcome estimates. The relapse-rate result and numerical secondary outcomes are not reported in the registry record, so the intended statistical question cannot be answered from the posted outcome information. The safety counts can be described, but they do not provide a comparative assessment.

For biostatistical interpretation, this makes the boundary between design intent and evidence especially important. The expected relapse figures in the endpoint description are assumptions, while the outcome results are absent. Keeping those distinct prevents a study rationale from being mistaken for a finding and clarifies what additional reporting would be needed to evaluate precision, follow-up, and comparative effects.

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 main limitation for interpreting efficacy is that a numerical primary relapse-rate result is not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported. The record therefore does not allow assessment of the event estimate, its precision, or the time-to-event outcomes.

The single-group design has no concurrent control arm, so it cannot directly estimate a treatment contrast. The study enrolled 17 participants, and the record does not report the distribution of participants across the planned risk categories. It also does not report the participant-level characteristics needed to understand the composition of the enrolled group, including age distribution and disease-specific enrollment.

The detailed treatment regimen and actual treatment received are not reported in the registry record beyond the description of risk-adapted treatment and up to 7 cycles of low-dose azacitidine. The rationale for the enrollment of 17, a formal sample-size justification, and the statistical analysis plan are not reported. The record does not describe missing-data handling, follow-up completeness, analysis populations, interim analyses, or multiplicity procedures.

Safety information is descriptive and lacks a concurrent comparison group. Further event-level details, including timing and treatment relationship, are not reported in the registry record. The reported counts and terms cannot by themselves establish causation or comparative safety. These limitations apply to interpretation of the posted registry information and do not imply that unreported procedures or analyses did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation — NCT02458235.
• Registry record last updated 2020-10-12; status last verified 2020-10.
• Results first posted 2020-10-12.
• 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

NCT02458235 is a completed phase II, single-group study sponsored by the University of California, San Francisco. It enrolled 17 participants and evaluated azacitidine with donor lymphocyte infusion after allogeneic stem cell transplantation. The intended population included pediatric and young adult patients with hematologic malignancies; listed conditions included acute myelogenous leukemia, acute lymphoid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome.

The primary endpoint was relapse rate, defined as the percentage of participants who relapsed up to 2 years. Median relapse-free survival and median time to relapse were listed as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. Safety entries list 10 participants affected by serious adverse events, 17 affected by other adverse events, and 0 deaths. The study has no concurrent comparator, and the detailed statistical plan and analysis populations are not reported in the registry record.