Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies (NCT03151057), a randomized phase 1 study. The primary outcome is Treatment-limiting Toxicities Will be Defined as Idelalisib Interruption for >14 Days, or Other >3 Adverse Events as Defined by CTCAE IV Not Captured in the Protocol for Dose De-escalation..

2. Clinical Question

The trial was designed to evaluate the safety of post-transplant idelalisib maintenance in patients with B-cell malignancies. Its stated safety concerns include cytopenias, donor chimerism, the incidence and severity of acute graft versus host disease, and gastrointestinal tolerance. Event-free survival at one year and exploratory immune-biomarker and lymphoma-cell sequencing analyses were listed as secondary outcomes.

The practical statistical question is therefore about safety-event occurrence and how clearly the registry records it, rather than an estimate of treatment benefit. The posted primary outcome values are 9 participants for idelalisib and 7 for placebo. Because these counts match the respective arm sizes, and because the registry does not provide further endpoint-level detail or a two-arm analysis, they should not be interpreted as establishing that every participant met the treatment-limiting toxicity definition. The meaning of those counts remains insufficiently clear in the registry record.

3. Trial Design

NCT03151057, titled “Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies,” is recorded as a phase 1, randomized, double-blind, parallel-group trial comparing idelalisib with placebo. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The record lists enrollment of 16 and describes patients with B-cell hematologic malignancies undergoing allogeneic HSCT.

The study began on 2018-07-31, had a primary completion date of 2022-06-20, and is marked terminated. The reason for termination is not reported in the registry record. The record does not report further information about how randomization was generated or implemented, who was masked, or whether masking was maintained throughout follow-up. “Double” masking is the registry’s designation; the identities of the masked roles are not reported.

The active arm is listed as idelalisib 100mg, and the comparison arm as placebo oral tablet. The idelalisib arm description specifies twice-daily dosing beginning +90 (+/- 10) days after transplant, but the description ends before providing a complete treatment duration. The placebo description specifies twice-daily dosing beginning +90 (+/- 10) days after allogeneic HSCT and continuing through Day 270 post transplant. The primary outcome timeframe is Day 90 - Day 270 post transplant.

The primary purpose described in the record is safety evaluation, not a stated efficacy comparison. The listed safety assessments include cytopenias, donor chimerism, acute graft versus host disease, and gastrointestinal tolerance. Event Free Survival at One Year and exploratory biomarker and sequencing work are listed as secondary outcomes. The registry lists 3 outcome measures and 2 secondary outcomes, but no analyses are posted. The protocol, detailed statistical analysis plan, and reasons for ending the trial 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 Treatment-limiting Toxicities Will be Defined as Idelalisib Interruption for >14 Days, or Other >3 Adverse Events as Defined by CTCAE IV Not Captured in the Protocol for Dose De-escalation., measured over Day 90 - Day 270 post transplant.

The primary outcome is a count of participants with treatment-limiting toxicities during Day 90 - Day 270 post transplant. The definition includes idelalisib interruption for >14 days, or other >3 adverse events as defined by CTCAE IV that were not captured in the protocol for dose de-escalation. It is intended to capture toxicities serious or persistent enough to limit treatment, which is relevant to a safety-focused maintenance study.

Using a participant count can make an outcome easier to interpret than a count of repeated events: a participant who has several events may still contribute as a participant with an event, depending on the outcome definition. Here, however, the registry does not clarify how the alternative parts of the definition were applied, how participants with multiple qualifying events were handled, or whether all listed values reflect participants meeting the complete definition. Those details are not reported in the registry record.

The registry posts primary outcome values of 9 for idelalisib and 7 for placebo, with the unit identified as participants. Those values are the same as the arm sizes recorded for the outcome. No further endpoint-level breakdown, uncertainty estimate, or treatment comparison is posted, and the results are not sufficient to determine whether the count represents participants meeting the stated treatment-limiting toxicity criteria. The record also does not report how missing or incomplete endpoint observations were handled.

The endpoint is therefore best read as the registry’s reported participant counts under its stated safety outcome, not as a fully documented estimate of the frequency or relative risk of treatment-limiting toxicity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical features shape what can be concluded from this record. The first is the distinction between a trial design and a reported analysis. Randomization assigns participants to groups by chance, which can help make a comparison less vulnerable to systematic differences at baseline. Double masking can reduce the influence of expectations on care and outcome assessment. These are general purposes of the methods. The registry records randomized, double-blind, parallel-group design, but does not provide the randomization procedure, masking roles, or an analysis plan. A design designation alone does not show how well these protections were implemented.

What does the primary count represent?

The primary outcome is described as a count of participants with treatment-limiting toxicities, with a specified post-transplant timeframe and criteria involving treatment interruption or adverse events. A participant count is a binary-type outcome at the individual level: each participant is classified according to whether the defined outcome occurred. The registry reports the unit as participants and posts values of 9 for idelalisib and 7 for placebo. It does not make clear whether these values are counts of participants meeting the outcome definition, nor does it give a criterion-specific breakdown. Because the counts match the arm sizes, additional clarification is important before interpreting them as endpoint events.

The registry indicates that a two-arm comparison for a binary endpoint is not estimable. In general, a comparative analysis of a binary outcome needs interpretable event and non-event information in each arm. If endpoint status is unavailable, ambiguous, or otherwise prevents estimation, the analysis cannot provide a meaningful treatment contrast. The record does not explain the specific reason the comparison was not estimable. It would be inappropriate to infer that reason from the counts alone.

Why does precision matter?

A point estimate, when available, describes the observed contrast in a sample. A confidence interval is a general statistical tool that describes uncertainty around an estimate and the range of effects reasonably compatible with the data under the analysis assumptions. No confidence interval is posted for the primary outcome. Without one, and with the comparison marked not estimable, the registry does not quantify the precision of a treatment contrast. This is distinct from whether an observed count is large or small: counts alone do not communicate how uncertain an underlying event frequency may be.

Small groups commonly yield imprecise estimates, especially for uncommon outcomes. This is a general statistical issue, not an estimate of precision specific to this trial. The record does not provide an inferential test, a model, or an adjusted effect estimate for the primary endpoint. It therefore does not support statements about statistical significance, nor does the absence of a posted result establish that the groups were equivalent.

How should safety counts be read?

The serious and other adverse-event summaries are descriptive counts of affected participants within each group. In general, these summaries answer how many participants were recorded with an event category, not whether treatment caused the event. A randomized comparison can support causal interpretation when its design, endpoint definitions, follow-up, and analysis are adequately documented, but adverse events also require clinical attribution and appropriate methods. The registry does not give event-level timing, duration, severity for all events, attribution, or a comparative safety analysis. The listed counts should be treated as reported observations rather than causal estimates.

The serious-event terms include reported percentages for neutrophil count decreased, increased alanine transaminase (ALT), increased aspartate transferase (AST), lung infection, diarrhea, and nausea and vomiting. These percentages are registry entries; they should not be reinterpreted as comparative effects. The record does not clarify the denominator or analysis details for each term beyond the percentages and arm-level risk counts displayed in the adverse-event data.

What do the planning illustrations mean?

The record describes sample-size illustrations based on fractions of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event outcomes, the stated convention is a total number of events; for other outcomes, it is participants per arm. These are planning illustrations, not the trial’s own design justification and not observed power. The registry does not report a sample-size justification for the trial. No specific illustration values are included in the record details, so no numerical planning result can be interpreted.

In general, a planning calculation asks how much information a future study might need under specified assumptions. Its result depends on the assumed effect and other design choices. A calculation built from an observed effect is not independent confirmation of that effect, and its assumptions should not be confused with a prespecified protocol target. The illustrations cannot repair the lack of an estimable primary comparison in the posted results.

What is not documented?

The registry lists 3 outcome measures, 2 secondary outcomes, and no posted analyses. It does not report an analysis population, a missing-data strategy, interim analyses, multiplicity adjustment, or the statistical model used for any endpoint. These omissions matter because analysis choices affect interpretation, particularly when multiple outcomes are considered or when some participant outcomes are unavailable. None of those choices can be reconstructed from the outcome counts. The appropriate conclusion is limited to describing the registry’s posted observations and identifying where the record does not support a statistical comparison.

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("Idelalisib 100mg", "Placebo Oral Tablet")
n      <- c(9, 7)
events <- c(9, 7)
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  Idelalisib 100mg  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7
ARM  Placebo Oral Tablet  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including a primary safety outcome and secondary outcomes of Event Free Survival at One Year and exploratory biomarker and sequencing analyses. It posts no analyses. The record does not report whether formal hypotheses were tested across these outcomes, whether any adjustment for multiple comparisons was planned, or how exploratory analyses were distinguished from confirmatory analyses.

Multiplicity is a general concern when several outcomes or analyses are examined: the chance of at least one apparently unusual result can increase when many tests are performed. This does not establish that a multiplicity problem occurred in this trial. The registry record does not report a statistical plan or adjusted results, so the handling of multiplicity cannot be assessed.

Missing-data handling is also not reported. The record does not describe whether endpoint observations were complete, how participants with unavailable outcomes were handled, or whether the posted counts use an intention-to-treat, per-protocol, safety, or other analysis population. The primary outcome counts matching the arm sizes do not answer these questions or establish how event status was coded.

The trial is marked terminated, but the reason for termination and any consequences for data collection are not reported in the registry record. The record also does not report interim analyses or stopping rules. These omissions limit assessment of the analysis process and the risk of bias, but they do not justify assuming that any particular analysis or interim review occurred.

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: neutrophil count decreased (44.4%), increased alanine transaminase (alt) (28.6%), increased aspartate transferase (ast) (28.6%), lung infection (22.2%), diarrhea (22.2%).

The registry reports serious adverse events for participants recorded as at risk in each arm. In the idelalisib group, 7 of 9 participants were affected; in the placebo group, 4 of 7 were affected. Other adverse events were recorded for 9 of 9 participants in the idelalisib group and 7 of 7 in the placebo group. The record lists deaths for 2 participants in the idelalisib group and 0 in the placebo group.

These are descriptive safety summaries, not treatment-effect estimates. The record does not provide a statistical comparison, event timing, individual event histories, or attribution of events to study treatment. The presence of a death in a group does not by itself show that the study treatment caused it, and the absence of a recorded death in the other group does not establish that the risk was absent.

The registry also lists serious-event terms with percentages: neutrophil count decreased, 44.4%; increased alanine transaminase (ALT), 28.6%; increased aspartate transferase (AST), 28.6%; lung infection, 22.2%; diarrhea, 22.2%; and nausea and vomiting, 22.2%. These values should be read as the record’s reported percentages for event terms, not as estimates of comparative risk. The registry record does not supply additional detail sufficient to infer causation or clinical severity beyond the labels and counts it reports.

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

The results are meaningful as a record of what the registry reports: primary outcome participant counts for the idelalisib and placebo arms, arm-level adverse-event summaries, and several serious-event terms with percentages. The trial is identified as a randomized, double-blind phase 1 study focused on safety after allogeneic HSCT. These registry entries provide context for understanding the kind of evidence the trial was designed to collect.

They do not establish a precise comparative effect. The primary count values are 9 and 7, but the registry does not provide a usable two-arm binary analysis and explicitly indicates that the comparison is not estimable. The values match the arm sizes, while the record does not clarify whether every participant met the treatment-limiting toxicity definition. The counts therefore cannot be taken as a clearly interpretable estimate of how often the defined primary outcome occurred.

The serious adverse-event counts, other adverse-event counts, and deaths are also descriptive. They do not establish that idelalisib caused any particular event or that the observed arm patterns would persist in a larger study. The record does not provide an adjusted analysis, uncertainty intervals, event-level attribution, or sufficient endpoint detail to assess those questions. No treatment benefit or lack of benefit can be inferred from these safety summaries.

In general, a small randomized safety trial can identify potential tolerability concerns and help describe what was observed under study conditions. Its findings are most informative when outcomes and analysis populations are clearly defined and when estimates are accompanied by measures of uncertainty. The registry record does not report those details for the primary comparison. The terminated status adds context, but the reason for termination is not reported, so its implications for the results cannot be determined.

The sound conclusion is limited: the registry documents the trial design and selected safety counts, but does not provide enough information for a precise or causal comparison of treatment-limiting toxicity between the groups. The counts should be read with that limitation in view, not as a definitive ranking of the study regimens.

14. Why This Trial Matters Statistically

This trial matters statistically because it combines a randomized design with a small phase 1 safety setting after allogeneic HSCT. Such a design can organize observations under a controlled comparison, while the clinical context makes careful event definition and follow-up especially important. The record’s stated safety domains—cytopenias, donor chimerism, acute graft versus host disease, and gastrointestinal tolerance—show that safety assessment extended beyond a single event label.

The registry also illustrates why outcome definitions need to be linked clearly to reported values. The primary definition combines treatment interruption with adverse-event criteria, while the posted participant counts match the recorded arm sizes and the two-arm comparison is not estimable. Without an explanation of coding and endpoint status, even a simple count cannot be confidently interpreted as the number meeting the endpoint. This is not merely a technical issue: endpoint clarity determines what a reader can learn from the reported result.

Safety counts also require restraint. Serious adverse events, other adverse events, and deaths are important observations, but descriptive counts do not by themselves distinguish treatment-related events from events arising in the post-transplant setting. A transparent record of timing, attribution, severity, and analysis methods would help readers understand those observations; such details are not reported in the registry record.

Finally, the trial’s terminated status and absence of posted analyses make registry completeness consequential. The record does not state why the study ended or how missing information was handled. The study is therefore a useful example of the difference between having a randomized trial record and having an interpretable treatment-effect analysis. Statistical design contributes structure, but clear definitions, complete reporting, and appropriate uncertainty estimates are also needed to support inference.

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 the information recorded for this trial. The posted primary outcome values are participant counts of 9 for idelalisib and 7 for placebo, matching the arm sizes in the registry. The record does not explain whether these counts represent participants meeting the full treatment-limiting toxicity definition, nor does it provide counts separated by the interruption and adverse-event criteria. This ambiguity limits interpretation of the primary result.

The registry states that values are missing or not estimable for a two-arm comparison of the binary endpoint. It does not explain why the comparison could not be estimated, and no effect estimate or uncertainty interval is posted. The reason for termination is also not reported. These gaps prevent a reader from judging whether the missing comparison relates to endpoint coding, data availability, analysis choices, or another issue.

Further limitations include the absence of a reported analysis population, missing-data approach, detailed statistical plan, and analysis results. The registry does not identify the roles masked in the double-blind design or describe the randomization procedure. It also does not report event-level timing or attribution for the adverse events and deaths. The post-transplant setting is described, but the record does not provide participant characteristics that would allow assessment of group comparability or the reach of the findings.

The record lists secondary outcomes, including event-free survival and exploratory biomarker work, but does not post analyses for them. It does not report how multiplicity was handled or whether any interim analyses took place. These are absences in registry reporting, not evidence that particular procedures did or did not occur. Together, they restrict both the statistical interpretation of the primary outcome and the context available for understanding safety observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies — NCT03151057.
• Registry record last updated 2024-03-12; status last verified 2023-08.
• Results first posted 2024-03-12.
• 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

NCT03151057 is a terminated, randomized, double-blind, parallel-group phase 1 trial sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. It compares idelalisib 100 mg with placebo as maintenance after allogeneic HSCT in patients with B-cell hematologic malignancies. The record lists enrollment of 16, a start date of 2018-07-31, and a primary completion date of 2022-06-20.

The primary outcome is a participant count for treatment-limiting toxicities during Day 90 - Day 270 post transplant. The registry posts values of 9 for idelalisib and 7 for placebo, but does not provide an estimable two-arm comparison or clarify whether those counts represent participants meeting the full endpoint definition. Serious adverse events affected 7 of 9 participants in the idelalisib arm and 4 of 7 in the placebo arm; other adverse events were recorded for all participants at risk in both arms. Deaths are listed for 2 participants in the idelalisib arm and 0 in the placebo arm.

The record lists 2 secondary outcomes and 3 outcome measures, with no analyses posted. The reason for termination, analysis populations, missing-data methods, and statistical plan are not reported. The available results are descriptive and do not support a precise comparative estimate.