Study of Melphalan HCl for Injection (Propylene Glycol-free), Carmustine, Etoposide, Cytarabine (BEAM Regimen) and Autologous Stem Cell Transplantation for Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Melphalan HCl for Injection (Propylene Glycol-free), Carmustine, Etoposide, Cytarabine (BEAM Regimen) and Autologous Stem Cell Transplantation for Lymphoma (NCT01969435), a na phase 2 study. The primary outcome is Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events.

2. Clinical Question

The study is framed as an assessment of safety and toxicity in lymphoma patients receiving the BEAM regimen as myeloablative conditioning for autologous transplantation. Because it has no comparison group, its central question is descriptive: what adverse events were observed under this regimen during the stated assessment window? The registry also lists efficacy-related outcomes, including response rates and disease-free survival, as well as time to neutrophil and platelet engraftment. Their presence in the registry does not establish that results for those outcomes are available. The posted record does not provide results for them.

3. Trial Design

This is a completed Phase II study sponsored by Washington University School of Medicine. The registry records enrollment of 50 and a single-group model. Allocation is listed as NA, and masking is listed as none. The design therefore has no concurrent control arm and does not support a randomized comparison between alternative regimens. The registry record does not report a sample-size justification or a statistical design rationale.

Participants received a regimen combining carmustine, etoposide, cytarabine, and propylene glycol-free melphalan HCl before autologous stem cell transplantation. The schedule specifies carmustine by intravenous infusion on Day -7; etoposide and cytarabine by intravenous infusion twice a day on Days -6, -5, -4, and -3; melphalan by intravenous infusion on Day -2; and stem cell transplantation on Day 0. The registry does not state drug doses in the information.

The study start date is 2014-03-19, and the primary completion date is 2015-09-30. Its status is recorded as completed. The primary endpoint covers treatment-related non-hematologic adverse events from Day -7 through Day 30. The registry says that events were assessed using National Cancer Institute CTCAE version 4.0, with the outcome described as counts of events of grade 2 or higher occurring in 10% or greater of participants. Grade 2 diarrhea and grade 2 nausea/vomiting were not recorded.

The registry lists secondary outcomes that include response rates, disease-free survival, and time to neutrophil and platelet engraftment. Disease-free survival appears twice in the listed outcome names. The record does not explain that repetition or provide outcome estimates in the information available for this analysis. It also does not report the analysis population, detailed statistical plan, or procedures for handling missing observations.

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 Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events, measured over Day -7 through Day 30.

The primary endpoint concerns treatment-related non-hematologic adverse events during the period from Day -7 through Day 30. The registry describes event assessment using National Cancer Institute CTCAE version 4.0 and focuses on grade 2 or higher events occurring in 10% or greater of participants. It also states that grade 2 diarrhea and grade 2 nausea/vomiting were not recorded. The registry record does not give the primary endpoint’s event counts or participant-level results.

Safety endpoints are used to describe the types and frequency of unwanted events observed while participants receive a treatment regimen. A severity grading system gives a structured way to classify events, while a stated observation window defines the period covered by the assessment. The threshold in this endpoint description identifies which events were intended to be counted in the reported outcome; it does not mean that events outside that threshold could not occur.

The endpoint is described in terms of both event counts and the share of participants experiencing events, but the registry does not provide the primary results needed to interpret either. The serious adverse-event summary is a separate piece of registry information and should not be treated as a substitute for the specified primary endpoint. In particular, the serious-event summary does not report the full set of grade 2 or higher non-hematologic events requested by the primary endpoint description.

Without the primary outcome results, it is not possible to characterize the recorded frequency or range of qualifying non-hematologic toxicities from the registry information. The endpoint definition tells readers what the study intended to assess; it does not, by itself, establish what the assessment found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods determine what a study’s results can say, and the registry record establishes some design features but leaves many analysis details unreported. The distinction matters particularly for this study because it is single-group and its primary endpoint is described without accompanying results.

What does a single-group design show?

A single-group study observes outcomes among participants who received the study regimen. It can describe events recorded in that group, subject to how participants were enrolled, followed, and assessed. Without a comparator group, it cannot estimate a between-group treatment contrast. The registry lists allocation as NA and the model as single-group, so the study should not be interpreted as a randomized comparison. A treatment effect relative to another regimen is not available from this design as described.

In general, random allocation can help balance measured and unmeasured characteristics between groups, although it does not guarantee perfect balance. This study has no randomized allocation between groups, so there is no such randomized contrast to interpret. A descriptive event frequency remains different from a causal claim about what the regimen changed.

How should a binary event count be understood?

The primary outcome is described in terms of participants and adverse events. A binary event measure classifies whether an event is recorded or not recorded for a participant under a specified definition. Counts are easier to interpret when the event definition, assessment window, and denominator are clear. Here, the registry supplies a timeframe, a grading system, and an event threshold, but does not report the primary outcome counts or the population included in its analysis.

Event counts and participant counts are not interchangeable in every setting. One participant may experience more than one event, so a count of events can differ from a count of participants with at least one event. The registry’s primary endpoint description refers to number of events, while its unit is participants. The detailed results needed to determine how counts were tabulated are not reported in the registry record.

The threshold of grade 2 or higher and occurrence in 10% or greater of participants is part of the endpoint definition. It describes what qualifies for inclusion in the reported outcome, not a statistical test or proof that less frequent events did not happen. The note that grade 2 diarrhea and grade 2 nausea/vomiting were not recorded should be retained as a reporting detail; the registry does not give further explanation for it.

What do severity grading and observation time add?

As a general statistical and clinical measurement principle, severity grading standardizes how events are classified. It can make event descriptions more interpretable across participants, provided that assessments are applied consistently. A defined observation window also limits the period to which the findings apply. This endpoint’s window is Day -7 through Day 30, so it should not be assumed to capture events outside that period.

The record names National Cancer Institute CTCAE version 4.0 as the assessment standard. It does not provide details on who assessed events, whether assessments were blinded, how disagreements were resolved, or how events were attributed to treatment. Masking is recorded as none. These omissions constrain assessment of how consistently the outcome was measured and interpreted.

What can confidence intervals and hypothesis tests contribute?

In general, a confidence interval gives a range of values compatible with an estimate under a statistical model and its assumptions. Wider intervals indicate less precision, while narrower intervals indicate greater precision. A hypothesis test evaluates data relative to a specified null hypothesis and testing procedure. Neither an interval nor a p-value makes a result clinically important by itself; interpretation also depends on the outcome definition, estimate, study design, and uncertainty.

The registry information reports no primary endpoint estimate, confidence interval, or test result. It also lists 0 analysis entries. There is therefore no reported primary estimate whose precision or statistical significance can be evaluated. The absence of an analysis entry should not be replaced by a calculation from unrelated summary information.

How do sample-size illustrations differ from trial evidence?

In general, a sample-size calculation describes how much information a hypothetical study might need under specified assumptions. The planning assumptions stated for illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe planning based on a stated portion of an observed effect, not the actual allocation or analysis of this single-group study. Such illustrations are not observed power and do not show that a treatment effect was detected.

The registry does not report the trial’s own sample-size justification. It also does not report a comparator-group estimate that would support a randomized treatment-effect interpretation. Planning calculations cannot fill either gap. They should be read as hypothetical design exercises, separate from what was observed in this trial.

What remains unknown about the analysis?

The registry record does not report the statistical analysis plan, analysis population, missing-data methods, or multiplicity procedure. It also does not provide the primary endpoint results or results for the listed secondary outcomes. In general, an analysis population definition clarifies who contributes to a particular estimate, and a missing-data method clarifies how absent observations are handled. Without those details, readers cannot assess whether the reported participants and outcomes would represent all enrolled participants or how incomplete follow-up might affect results.

For rare or uncommon events, estimates can be imprecise, and the interpretation depends on both the number of observed events and the number of participants assessed. This is a general statistical consideration, not a claim about the unreported primary endpoint. The available serious adverse-event summary is limited and cannot stand in for the missing endpoint analysis. The registry’s design and reporting details therefore support a careful description of the study, but not a comprehensive statistical evaluation of its safety or efficacy findings.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and identifies a primary safety endpoint alongside secondary outcomes that include response rates, disease-free survival, and time to neutrophil and platelet engraftment. Disease-free survival appears twice in the listed secondary outcome names. The record does not explain whether the repeated entry represents separate assessments or a registry duplication. It also does not report a multiplicity procedure.

Multiplicity is a general statistical issue that arises when several outcomes or hypotheses are examined. The more questions assessed, the greater the chance that some results may appear notable by chance if no appropriate analysis plan is used. A stated analysis plan can clarify which outcomes are primary, how secondary results are interpreted, and whether adjustments or other controls are used. The statistical plan and any multiplicity approach are not reported in the registry record, so the handling of multiple outcomes cannot be assessed.

The registry lists 0 analysis entries, and the primary and secondary outcome results are not reported in the information. It is therefore not possible to review outcome-specific denominators, estimates, uncertainty, or tests. The record does not report the analysis populations or how missing data were handled. These details matter because incomplete assessments can affect which participants contribute to an outcome and the interpretation of event frequencies.

In general, missingness can arise for different reasons, and the implications depend on why observations are missing and how the analysis addresses them. No missingness pattern or method is reported. It would be inappropriate to infer that all enrolled participants completed every assessment, or to assume a particular imputation or censoring method.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: multi-organ failure due to sepsis (2.0%).

The registry’s serious adverse-event summary lists 50 participants at risk and 1 participant affected. It also identifies multi-organ failure due to sepsis as a serious adverse-event term reported at 2.0%. These are the serious-event figures recorded for the BEAM group. They should be read as registry summaries, not as the complete primary safety endpoint.

The primary endpoint is broader in scope: it concerns treatment-related non-hematologic adverse events of grade 2 or higher from Day -7 through Day 30, with an event threshold of 10% or greater. The serious-event summary does not provide those endpoint results. Seriousness and severity grading are different concepts in general: an event’s seriousness classification is not interchangeable with its CTCAE grade. The registry record does not provide enough detail to map the listed serious event to the primary endpoint definition.

The record also does not state in the information whether the serious event was judged to be treatment-related. The reported 2.0% is the registry’s listed percentage for the named serious-event term; it should not be treated as a newly calculated estimate or as evidence about comparative risk. With no control group, the serious-event summary cannot establish whether the regimen increased or decreased risk relative to an alternative.

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

The record establishes that a completed Phase II, single-group study evaluated a BEAM regimen containing propylene glycol-free melphalan in lymphoma patients undergoing autologous stem cell transplantation. It defines a primary safety endpoint and identifies a serious adverse-event summary. It does not provide the primary endpoint results, nor results for the listed secondary outcomes. The most important interpretive boundary is that an endpoint description is not an outcome finding.

The serious adverse-event summary reports 1 participant affected among 50 at risk and lists multi-organ failure due to sepsis at 2.0%. These figures are limited to the serious-event information recorded. They do not describe all adverse events, establish the number of grade 2 or higher non-hematologic events, or answer the primary safety question. Nor do they establish whether the reported event was considered related to treatment.

Because the study has no comparator, even fully reported event rates would be descriptive rather than a randomized estimate of how outcomes differ between regimens. Comparisons with results from other studies would also require caution because participant characteristics, outcome definitions, follow-up, and assessment practices may differ. The registry record does not provide enough information to make such comparisons.

The secondary outcome names indicate planned or registered areas of interest, including response rates, disease-free survival, and engraftment timing. They do not show what was observed. No conclusions about efficacy, disease control, or engraftment can be drawn from outcome names alone, and the registry does not report corresponding estimates in the information.

Accordingly, the record supports a description of the trial’s design and intended safety assessment, plus limited serious adverse-event reporting. It does not support a conclusion that the regimen is safe or unsafe, effective or ineffective, or better or worse than another approach. Those judgments would require complete outcome results, adequate context, and methods appropriate to the question.

13. Why This Trial Matters Statistically

This study illustrates why trial design and outcome reporting must be read together. A Phase II label and a defined safety endpoint identify the study’s purpose and measurement framework, but they do not supply the findings. Here, the registry describes a single-group regimen and a primary safety question, while the primary endpoint results are not reported in the information.

The distinction between event counts, participants affected, severity, and seriousness is also important. The primary endpoint targets grade 2 or higher non-hematologic events meeting a stated occurrence threshold. The separate serious adverse-event summary reports a participant count and a named term. Treating these measures as interchangeable would blur different aspects of safety and could misstate what the registry actually records.

The absence of a comparator is a central statistical feature, not a minor technicality. It means that observed outcomes cannot be contrasted with a concurrent control group to estimate a randomized treatment effect. Even a complete set of single-group outcomes would need to be interpreted as descriptive evidence, with limitations on causal attribution.

The record also demonstrates the value of transparent analysis reporting. Analysis populations, missing-data methods, and multiplicity procedures affect how readers assess estimates and uncertainty, but these are not reported in the registry information. A list of outcome names cannot substitute for numerical results, and planning assumptions cannot substitute for observed analyses.

For clinical researchers and biostatisticians, the key statistical lesson is disciplined interpretation: separate the design from the endpoint definition, distinguish serious events from the primary toxicity measure, and avoid turning absent results into conclusions. This preserves what the record can establish while making clear what remains unknown.

14. 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 major limitation specific to interpreting this study is the absence of reported primary endpoint results in the registry information. The record defines treatment-related non-hematologic adverse events of grade 2 or higher from Day -7 through Day 30, but supplies no corresponding endpoint estimates or counts. The serious adverse-event summary is not a substitute for those results.

The single-group design provides no concurrent comparator. Consequently, the study cannot support a randomized comparison of safety or efficacy between regimens. Allocation is listed as NA and masking as none. The record does not report an analysis population or detailed eligibility criteria, so the population contributing to each outcome cannot be characterized further from this information.

The registry does not report the statistical analysis plan, a sample-size justification, multiplicity procedures, or methods for handling missing data. It does not report outcome-specific denominators, confidence intervals, or test results. These omissions limit assessment of precision, completeness, and analytic choices. The secondary outcomes are listed without results, and disease-free survival appears twice among the outcome names without an explanation.

The primary endpoint’s event-count description does not clarify how recurrent events were handled or how event counts related to the participant unit. The record notes that grade 2 diarrhea and grade 2 nausea/vomiting were not recorded, but does not explain the reason. The serious-event summary also does not state in the information whether the reported event was considered treatment-related.

Finally, the schedule is given without drug doses in the information, and the registry does not provide further details on event assessment or follow-up beyond the stated primary timeframe. These limitations do not negate the recorded design information, but they constrain what can be concluded from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Melphalan HCl for Injection (Propylene Glycol-free), Carmustine, Etoposide, Cytarabine (BEAM Regimen) and Autologous Stem Cell Transplantation for Lymphoma — NCT01969435.
• Registry record last updated 2018-02-13; status last verified 2018-01.
• Results first posted 2016-11-11.
• 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.

18. Record Summary

NCT01969435 is a completed Phase II, single-group study sponsored by Washington University School of Medicine. It enrolled 50 participants and evaluated propylene glycol-free melphalan with carmustine, etoposide, and cytarabine as BEAM conditioning before autologous stem cell transplantation for lymphoma.

The primary endpoint was treatment-related non-hematologic adverse events of grade 2 or higher from Day -7 through Day 30, assessed using National Cancer Institute CTCAE version 4.0. The registry states that grade 2 diarrhea and grade 2 nausea/vomiting were not recorded, but does not report primary endpoint results. The serious adverse-event summary lists 1 affected participant among 50 at risk and multi-organ failure due to sepsis at 2.0%.

The registry also lists response, disease-free survival, and engraftment outcomes without reporting their results in the information. With no comparator and no reported primary analysis, the record supports a design and safety-reporting description, not a comparative conclusion.