Bendamustine HCL in Relapsed and Primary Refractory Hodgkin Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bendamustine HCL in Relapsed and Primary Refractory Hodgkin Lymphoma (NCT00705250), a na phase 2 study. The primary outcome is Determine the Overall Response Rate (RR) to Bendamustine HCL in Patients With Relapsed and Primary Refractory HL..

2. Clinical Question

In general, a response endpoint captures whether disease meets predefined criteria for improvement or disappearance during the specified assessment period. It is not itself a comparison of treatment against another option. In this single-group study, the endpoint was intended to describe responses among evaluable participants receiving bendamustine HCL. Without a reported response result, the record does not establish the size or precision of the observed response proportion.

3. Trial Design

This was a phase II, completed, single-group study sponsored by Memorial Sloan Kettering Cancer Center. The registry lists 36 participants as enrolled. The intervention was bendamustine HCL, with the arm description specifying 120mg/m^2. Allocation is recorded as NA and masking as none. These design features mean the registry describes a treatment group rather than a randomized comparison between treatment strategies.

The study title and primary objective focus on relapsed and primary refractory Hodgkin lymphoma. The brief description places the research in a setting where patients may be ineligible for transplant or may have disease that returns after transplant, and where treatment options are described as limited. The study's stated purpose was to find out the effect of bendamustine HCL for transplant-ineligible patients whose disease had not responded to treatment or had returned. The record does not provide further eligibility criteria or a detailed description of the enrolled participants.

The listed primary endpoint was overall response rate, defined as the percentage of evaluable participants achieving complete response or partial response. Its timeframe is stated as up to 3 years. The record contains one outcome measure, but no analysis is listed. The actual response proportion, the denominator used for that proportion, and any interval estimate or test result are not reported in the registry record.

Recruitment began in 2008-06, primary completion is listed as 2015-12, and the study status is completed. These dates describe the registry timeline, not the duration of treatment or follow-up for any individual participant. The registry record does not report details of treatment administration beyond the listed intervention and dose, the timing of response assessments, or the duration of follow-up actually achieved by participants.

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 Determine the Overall Response Rate (RR) to Bendamustine HCL in Patients With Relapsed and Primary Refractory HL., measured over up to 3 years.

The primary endpoint is the overall response rate: the percentage of evaluable participants whose best recorded response met the study definitions for complete response or partial response. A complete response was described as disappearance of all evidence of disease, with imaging-related qualifications for disease that was FDG-avid or PET positive, or variably FDG-avid or PET negative. A partial response required regression of measurable disease and no new sites; the description includes a 50% decrease in SPD of up to 6 largest dominant masses and additional imaging conditions.

In general, response rates are used in clinical studies to describe how often participants meet prespecified criteria for disease response. Combining complete and partial responses creates a single summary of participants meeting either response category, while not distinguishing the degree of response within that combined endpoint. The endpoint is expressed among evaluable participants, so its denominator depends on how evaluability was defined and how many participants met that definition. Neither detail is reported in the registry record.

The timeframe is listed as up to 3 years. This identifies the stated assessment window but does not tell readers when assessments occurred, which response was used if a participant had multiple assessments, or how missing assessments were handled. Most importantly, the registry record does not report the observed rate. The endpoint definition alone therefore describes what was to be measured, not the result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group response analysis estimate?

In general, a single-group response analysis estimates the proportion of participants in that group who satisfy the response definition. For this study, the intended outcome combined complete response and partial response among evaluable participants. The estimate would be a descriptive summary of the study group; it would not by itself estimate a difference from another treatment. Since no response count or response proportion is reported in the registry record, there is no posted estimate to interpret.

The analysis population matters because the endpoint uses the word evaluable. A response percentage can change depending on which participants are included in its denominator. For example, a study might define evaluability using the availability of a baseline assessment or a post-treatment assessment, but the registry record does not specify such rules, and those possibilities should not be assumed to be this study's protocol. The number evaluable and the handling of participants without response assessments are not reported.

What would an interval estimate add?

In general, a confidence interval expresses the uncertainty associated with an estimated response proportion. It is influenced by both the estimate and the amount of information available. A point estimate without an interval can conceal substantial uncertainty, particularly when the analysis population is limited. The registry record does not report an interval for the primary endpoint. It also does not report a p-value or an analysis comparing the observed response with a prespecified benchmark.

Confidence intervals are not a substitute for clear outcome definitions or complete reporting. Readers need the response numerator, the denominator, the assessment rules, and the interval method to understand what an interval summarizes. Those analysis details are not reported in the registry record. No interval should be inferred from enrollment alone.

Why does the absence of a control group matter?

In general, a concurrent control group helps distinguish outcomes observed during treatment from outcomes that might occur under a different treatment strategy or without the intervention. In a single-group design, there is no randomized comparison to balance prognostic factors across treatment groups. Changes in disease status can be described, but the design cannot separate the intervention's contribution from other influences as directly as a controlled comparison could. This is a general design consideration, not a finding about the participants in this study.

The record lists no comparator and no allocation to multiple groups. Therefore, concepts such as a between-group treatment effect, relative risk, or treatment-effect confidence interval do not describe the primary analysis recorded for this study. The registry does not report a comparison with a historical response rate, and no such benchmark should be presumed.

What can be said about the sample-size calculations?

The sample-size material is described as a planning illustration computed from the observed effect, not as the study's own design. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the assumed effect to detect is a stated fraction of the observed effect. Those are planning assumptions for an illustration, not evidence that the trial used that design. They do not change the fact that the registry records a single-group study.

Such planning calculations answer a hypothetical question about the number of participants that might be needed under specified assumptions. They are not an observed trial outcome and do not establish the probability that the completed study detected an effect. In particular, they should not be interpreted as observed power. The registry record does not report a protocol-based sample-size justification, and it does not report a prespecified effect size or rationale for the enrollment target. The planning illustration cannot fill those gaps.

How should safety summaries be interpreted?

In general, safety-event summaries require attention to the event definition, observation period, denominator, and whether counts refer to participants or events. A participant may experience more than one event, so participant counts and event counts are not interchangeable. The safety information lists 36 participants at risk and 5 affected by serious adverse events. It also lists percentages for selected serious terms. The registry record does not provide additional detail about event timing, severity grading, or whether each term represents participants or event episodes beyond the labels shown.

The term-level percentages are descriptive and have no control-group contrast. They should not be treated as estimates of excess risk attributable to treatment. In general, rare or uncommon events can be estimated imprecisely in a small study, and a lack of an entry for a specific event is not proof that the event did not occur. Deaths are not reported in the registry record's safety summary.

The number of analyses is recorded as zero. This does not supply an analysis plan, and it does not establish that no analyses were performed outside the registry entry. Statistical methods beyond the planning illustration, including methods for missing data, endpoint estimation, or interim monitoring, are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure: overall response rate, defined using complete or partial response among evaluable participants. It does not report an outcome-analysis result. Although one primary endpoint is listed, the registry record does not describe a broader statistical analysis plan, specify whether additional endpoints were examined, or explain how multiple analyses or comparisons would be handled. Multiplicity procedures are therefore not reported in the registry record; it would not be justified to assume that multiplicity was or was not addressed in analyses outside the entry.

Missing-data handling is also not reported. The endpoint denominator is described as evaluable participants, but the record does not define evaluability, state how many participants were evaluable, or explain how participants with missing response assessments were treated. It does not say whether participants without an assessment were excluded, counted as not responding, or handled using another rule. Those choices can affect an estimated response rate, so the absence of this information limits interpretation.

The record gives enrollment as 36 but does not state how many participants received treatment, completed treatment, had outcome assessments, or contributed to the primary endpoint analysis. The population used for that analysis is not reported in the registry record. Nor does the entry report whether analyses followed an intention-to-treat principle, a per-protocol approach, or another definition. These are not interchangeable labels, and none should be assigned without documentation.

Interim analyses and stopping rules are not reported in the registry record. The sample-size material is identified as a planning illustration rather than the study's own design justification. Together, these omissions mean that the statistical framework for the completed study cannot be reconstructed from the registry entry alone.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (5.6%), pneumonia (2.8%), self-limited gross hematuria (2.8%), vomiting (2.8%).

The safety summary lists 36 participants at risk for serious adverse events, with 5 affected. The listed serious adverse event terms and percentages are febrile neutropenia at 5.6%, pneumonia at 2.8%, self-limited gross hematuria at 2.8%, and vomiting at 2.8%. These are the figures recorded for this study group; they are not a comparison with another treatment group.

In general, an adverse-event percentage describes frequency within a defined safety population, but interpretation also depends on how events were collected and whether the percentage refers to participants or event episodes. The registry information does not provide additional detail on event timing, duration, severity grading, or term-specific counts. The reported percentages should therefore be read as registry summaries, not as a full account of each event or its relationship to treatment.

The safety information also lists 36 participants at risk and 36 affected for other adverse events. This is distinct from the serious adverse event summary. The deaths field is not populated, so deaths are not reported in the registry record; an unreported value should not be interpreted as zero. Without a control group, the study cannot quantify comparative safety or isolate treatment-associated risk.

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

This study record matters as a description of a phase II investigation of bendamustine HCL in relapsed and primary refractory Hodgkin lymphoma. It identifies the intended population, a single treatment group, the listed dose, an overall response endpoint, and selected safety information. It also records enrollment of 36 and completed status. These registry entries provide context for understanding what the study set out to assess.

The central efficacy result is not reported in the registry record. There is no observed overall response rate, response numerator, evaluable denominator, or precision estimate in the entry. Consequently, the recorded information cannot establish how often participants achieved complete or partial response, nor how precisely such a proportion was estimated. The treatment's effect on the endpoint cannot be characterized from the endpoint definition alone.

Even if the response estimate were reported, this design would remain a single-group study. In general, outcomes in a treated group do not furnish the same evidence as a randomized comparison with a concurrent control. The registry entry does not provide a treatment contrast and does not support a direct comparative conclusion. It also does not report enough detail about analysis populations or missing assessments to determine how the response denominator was formed.

The safety figures describe reported serious adverse events within the study group, but there is no control group for comparative interpretation. They do not establish whether an event is more or less common than it would be under another strategy. The unpopulated deaths field is not evidence of zero deaths, and selected term percentages are not a complete characterization of safety.

In general, a clinical trial result is best interpreted alongside its endpoint estimate, uncertainty, analysis population, and design. Here, the registry record supplies the trial framework and selected safety summaries, but not the primary endpoint result or its statistical analysis. The appropriate conclusion is about the information recorded: key efficacy and analysis details are unavailable in the registry record. No claim about treatment benefit or lack of benefit follows from that absence.

13. Why This Trial Matters Statistically

The statistical importance of this study lies partly in the distinction between a planned question and a reported result. The registry record clearly identifies a response-rate question in a population with relapsed or primary refractory Hodgkin lymphoma. Yet it does not report the response estimate or the analysis that would answer that question. Readers therefore cannot judge either the magnitude of the observed response proportion or its precision from the record.

The study also illustrates why the analysis denominator needs to accompany a response rate. The endpoint applies to evaluable participants, while enrollment is reported as 36. The record does not state how many participants were evaluable or how evaluability was defined. In general, a response proportion without these details can be difficult to interpret because readers cannot tell exactly which participants it represents.

Its single-group design is another important statistical feature. A response proportion can describe outcomes in the study group, but no concurrent control is available to anchor a comparative estimate. This is not a defect in the arithmetic; it is a limit on the question the design can answer. The registry record does not report a comparator or randomized allocation, so the study entry cannot provide a treatment-versus-control effect.

Finally, the entry separates safety reporting from efficacy reporting: selected serious adverse event information is present, while the primary response result is not. That contrast makes completeness of outcome reporting consequential. Statistical interpretation depends not only on a stated endpoint but on the estimate, denominator, uncertainty, and analysis rules. Their absence leaves important questions unresolved, regardless of the study's completed status.

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 most direct limitation of this registry record is that it does not report the primary response result. The overall response rate, number of complete responses, number of partial responses, and number of evaluable participants are all not reported in the registry record. No confidence interval or statistical test for the primary endpoint is listed. Readers cannot quantify the study's response findings or assess their precision from this entry.

Important details about the endpoint analysis are also missing. The timeframe is described as up to 3 years, but assessment timing, response-assessment procedures, and the selection of a response when assessments differ are not reported. The evaluability definition, handling of missing response assessments, and analysis population are not reported. These omissions make it difficult to know how the intended outcome would have been calculated.

The design is single-group, with allocation listed as NA and masking as none. There is no concurrent comparator in the record. Thus, the study entry cannot support a randomized treatment comparison. The registry record also does not provide detailed eligibility criteria, participant characteristics, treatment exposure, or follow-up completeness, limiting assessment of how the enrolled group relates to the target population described in the summary.

The serious adverse event summary is limited to the recorded at-risk and affected counts and selected terms with percentages. The deaths field is not reported in the registry record. Further safety details, including event timing and term-specific counts, are not posted by the entry. These limitations are specific to the information recorded and should not be mistaken for proof that unreported outcomes or analyses did not exist elsewhere.

The sample-size calculations are identified as a planning illustration based on the observed effect, not the study's own design. A protocol-based sample-size justification, interim-analysis plan, and broader statistical analysis plan are not reported in the registry record. The illustration cannot substitute for those methods or establish the statistical properties of the trial as conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bendamustine HCL in Relapsed and Primary Refractory Hodgkin Lymphoma — NCT00705250.
• Registry record last updated 2017-03-03; status last verified 2017-01.
• Results first posted 2017-01-19.
• 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

The registry record describes a completed phase II, single-group study of bendamustine HCL in relapsed and primary refractory Hodgkin lymphoma. Memorial Sloan Kettering Cancer Center is listed as sponsor. Enrollment was 36, the intervention is listed at 120mg/m^2, allocation is NA, and masking is none. Recruitment began in 2008-06, and primary completion is listed as 2015-12.

The primary endpoint was the percentage of evaluable participants achieving complete or partial response, assessed over up to 3 years. The response result, evaluable denominator, and statistical analysis are not reported in the registry record. Safety information lists 5 participants affected by serious adverse events among 36 at risk, along with selected term percentages. Deaths are not reported in the registry record. The entry describes study design and selected outcomes, but does not provide the primary efficacy estimate or enough analysis detail to assess it.