Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma (NCT00601718), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose of Vorinostat.

2. Clinical Question

3. Trial Design

This was a phase I/II study sponsored by the University of Washington. It is marked completed, with a start date of 2007-12 and a primary completion date of 2010-06. The recorded enrollment was 29. The registry identifies a single-group model rather than a randomized comparison; allocation is listed as not applicable, and masking as none.

The regimen combined vorinostat, ifosfamide, carboplatin, and etoposide. Participants who were CD20-positive also received rituximab. The treatment description specifies vorinostat by mouth once daily on days 1-5, continuous intravenous ifosfamide over 24 hours and intravenous carboplatin over 1 hour on day 4, and intravenous etoposide over 1 hour on days 3-5. Rituximab was given intravenously once on day 3, 4, or 5 for CD20-positive participants. The described treatment repeats every 21 days for 2 courses, although the remainder of that regimen description is incomplete in the record.

The primary outcome is maximum tolerated dose of vorinostat, with a stated assessment timeframe of 28 days after the last dose. The endpoint unit says milligrams twice daily for five days, while the treatment description says once daily on days 1-5. The registry does not explain this difference. Details of the dose-finding procedure, dose levels, or criteria used to define the maximum tolerated dose are not reported in the registry record.

The study also lists pharmacological, laboratory biomarker, and gene expression analyses. Four outcome measures are recorded, but the registry record contains no analysis entries. It therefore does not provide an estimate for the primary outcome or an inferential comparison of the regimen’s effects.

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 Maximum Tolerated Dose of Vorinostat, measured over 28 days post last dose of study drug.

The primary endpoint is the maximum tolerated dose of vorinostat. The registry gives the unit as milligrams twice daily for five days and the assessment timeframe as 28 days after the last dose of study drug. No endpoint value is reported in the registry record.

In general, a maximum-tolerated-dose endpoint is used in early-phase research to characterize the dose that can be administered under the study’s safety rules. It is distinct from an endpoint that directly measures tumor response or survival. The registry’s description of the study also mentions side effects and how well the regimen works, but the primary outcome named in the record is a dose measure, not a reported estimate of clinical benefit.

The record does not state the dose levels tested, how dose increases or reductions were governed, or which adverse events counted toward the dose-limiting criteria. Those details are important for interpreting a maximum-tolerated-dose estimate. The endpoint unit refers to twice-daily administration, whereas the regimen description says vorinostat was given once daily on days 1-5. The registry does not reconcile these descriptions, and no numerical dose result is available to clarify the intended interpretation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow?

A single-group study observes participants receiving the study regimen without a concurrent control group. In general, this design can describe what happened among treated participants and can support early investigation of tolerability or dose. It does not provide the randomized comparison needed to estimate how outcomes would differ under another treatment. This distinction matters for the current study: the registry identifies one treatment group and explicitly indicates that the study is not a randomized comparison.

Random allocation, when used, helps create groups that are comparable on average with respect to measured and unmeasured characteristics. Without it, comparisons with an external population or historical experience can be affected by differences in eligibility, disease mix, assessment, and care. No external comparator or controlled efficacy estimate is reported in the registry record. The listed diagnoses cover multiple lymphoma types and stages, but the number of enrolled participants in each diagnosis group is not reported.

How should the maximum tolerated dose be understood?

In general, dose-finding studies use predefined safety observations to guide assessment of whether a dose is tolerable. The maximum tolerated dose is meaningful only in relation to the study’s dosing schedule, observation window, and rules for identifying dose-limiting toxicity. The registry names the endpoint and gives a 28-day post-treatment timeframe, but it does not report the dose-finding algorithm, toxicity criteria, dose levels, or the endpoint value. It is therefore not possible to reconstruct the dose decision from the record.

The registry’s endpoint unit describes vorinostat in milligrams twice daily for five days, whereas the treatment description specifies once-daily administration on days 1-5. No explanation of this difference is reported. The details of dose changes over the course of the study are also not reported. These gaps limit interpretation even apart from the missing endpoint result.

What does statistical uncertainty mean?

In general, a confidence interval describes a range of values reasonably compatible with the data under a specified statistical model. A narrow interval indicates greater precision than a wide interval, but an interval does not correct for bias in study design or measurement. No confidence interval for the primary endpoint or a treatment effect is reported in the registry record. Without a numerical estimate and its uncertainty, the precision of the primary result cannot be assessed.

A p-value, in general, summarizes how unusual data would be under a specified null hypothesis and statistical model. It does not measure the probability that a treatment works, and it does not describe clinical importance. The record contains no analysis entries and reports no p-value or hypothesis test for the primary endpoint. The single-group design also means that a test against a treatment comparator is not reported.

What are the planning assumptions?

The stated planning assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The calculation is described as a planning illustration based on the observed effect, with the effect to detect expressed as a fraction of that observed effect. These assumptions are not the trial’s own design: the registry describes a single group, not equal allocation between two arms. The numerical planning values and the observed effect used for them are not reported in the registry record.

Such sample-size calculations are hypothetical planning illustrations. They do not indicate the probability that this completed study detected an effect, and they are not observed power. In general, observed power is not a substitute for reporting the estimate and its uncertainty. Because the numerical planning values and the trial’s outcome estimate are unavailable, no conclusion about the adequacy of enrollment for a particular effect can be drawn from those assumptions.

Why does over-dispersion matter in general?

For count outcomes, a simple model may assume that the variability is determined by the average count. Over-dispersion means the observed variability is greater than that assumption allows. If it is ignored, standard errors can be too small and intervals or tests can appear more precise than warranted. This is a general statistical consideration; the registry does not report a count-outcome model, an over-dispersion assessment, or a model-based treatment estimate for this study.

The record lists four outcome measures and no analysis entries. It does not describe a statistical analysis plan, model specifications, covariate adjustment, or interim analyses. Accordingly, the posted information does not support attributing a particular analytical method to the investigators beyond the design and outcome details explicitly recorded.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity refers, in general, to the interpretive problem that arises when multiple outcomes, comparisons, time points, or subgroups are examined. If many statistical tests are performed, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. The registry lists four outcome measures, but it does not report a multiplicity strategy or analysis entries. It is not possible to determine which outcomes were treated as primary or whether any adjustment for multiple testing was used beyond the named primary outcome.

Missing-data methods describe how analyses handle participants without an observed measurement or with incomplete follow-up. The registry record does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not specify analysis populations, such as which participants were included in each outcome analysis. Enrollment of 29 does not establish that all participants contributed data to every outcome.

The record does not report interim analyses or a statistical analysis plan. It therefore cannot establish whether the reported outcome definitions and analysis decisions were fixed before results were examined. These omissions do not prove that particular procedures were or were not used; they mean the procedures are not reported in the registry record. With no analysis entries and no primary endpoint value, the effects of missing data or multiplicity cannot be evaluated from the posted information.

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 (10.3%), dyspnea (3.4%), encephalopathy (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%).

The safety record lists 29 participants at risk for serious adverse events and 10 affected. For other adverse events, 29 were at risk and 25 were affected. These are counts of affected participants in the single treatment group, not comparisons between treatment arms. No death count is reported in the registry record.

The most frequently listed serious-event term is febrile neutropenia at 10.3%. Dyspnea, encephalopathy, nausea/vomiting, diarrhea, and hypotension are each listed at 3.4%. These percentages are reported as recorded; they should not be added together. In general, one participant may experience more than one event term, so categories need not represent distinct groups of people.

Serious adverse events and other adverse events are separate registry summaries. The figures describe events recorded during the study, but the registry information does not establish that every event was caused by the regimen. Without a control group, comparative rates cannot be estimated from this study. Details such as event severity grading, timing, duration, and individual participants’ event histories are not reported in the registry record.

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

The record describes a completed phase I/II, single-group study enrolling 29 participants and evaluating a regimen of vorinostat, ifosfamide, carboplatin, and etoposide, with rituximab for CD20-positive participants. It identifies maximum tolerated dose of vorinostat as the primary outcome and gives its assessment timeframe. It also records serious and other adverse-event counts. These registry entries provide a limited account of the study’s design and safety reporting.

The primary outcome value is not reported in the registry record. No statistical analysis entries are present, and no comparative treatment-effect estimate is reported. Consequently, the record does not establish the dose found to be maximally tolerated, quantify uncertainty around that dose, or provide a treatment-effect estimate for lymphoma outcomes. The absence of a control group also prevents a randomized comparison with another treatment.

In general, an early-phase dose outcome and an efficacy outcome answer different questions. A dose-finding result concerns tolerability under specified rules; an efficacy result concerns outcomes such as tumor response or time to an event. The registry’s stated purpose refers to studying how well the regimen works, but the available record does not report an efficacy estimate. No conclusion about benefit or lack of benefit follows from a missing result.

The safety counts indicate that adverse events were recorded in the treatment group, including serious events. They do not show what would have occurred under a different regimen, and the registry does not report the death count or detailed event-level information. Interpretation should therefore remain descriptive rather than comparative. The record’s broad diagnosis list and lack of diagnostic breakdown further limit conclusions about how findings might vary across lymphoma types.

13. Why This Trial Matters Statistically

This study illustrates why a registry record’s design and outcome reporting need to be read together. The trial is labeled phase I/II and names a maximum-tolerated-dose endpoint, which signals an early-stage focus on dose and tolerability. Yet the endpoint’s numerical result is not reported. Enrollment and a completed status cannot substitute for the missing dose estimate or its uncertainty.

The single-group structure is also central to interpretation. A regimen can be described in relation to the participants who received it, but without a randomized comparator, the study does not estimate a treatment difference against another approach. The range of lymphoma conditions listed makes the participant mix important as well; the record does not provide counts by diagnosis, so readers cannot assess how enrollment was distributed across those conditions.

Safety reporting offers concrete descriptive information: 10 participants were affected by serious adverse events and 25 by other adverse events among 29 at risk. At the same time, the absence of a death count and detailed event information limits the picture. Those counts should not be converted into comparative claims.

Finally, planning assumptions must not be confused with evidence generated by the study. The described sample-size approach assumes a two-arm allocation even though the trial itself is single-group, and the numerical planning illustrations and observed-effect estimate are not reported in the registry record. This distinction helps prevent planning calculations from being mistaken for an actual treatment result or observed power.

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.

Several trial-specific gaps constrain interpretation. The registry names maximum tolerated dose as the primary endpoint but does not report its value. It also does not provide the dose-finding rules, dose levels tested, or toxicity criteria used to determine the endpoint. The endpoint unit says twice-daily dosing, while the treatment description says once daily on days 1-5; the record does not resolve this difference.

The study has a single treatment group and no randomized comparator. The registry therefore does not provide a controlled estimate of treatment effect. Enrollment was 29, but the number of participants in each listed lymphoma diagnosis or disease stage is not reported. Without that breakdown, the range of diagnoses cannot be translated into subtype-specific findings.

Four outcome measures are listed, but there are no analysis entries. The record does not report missing-data handling, analysis populations, interim analyses, an analysis plan, or a multiplicity strategy. It also does not provide a primary endpoint estimate or confidence interval. These details are not reported in the registry record, so the robustness and precision of outcome analyses cannot be assessed.

Safety reporting includes affected-participant counts and selected serious-event terms, but the death count is not reported. Event timing, severity grading, duration, and attribution are also not reported. Finally, the described planning assumptions refer to equal allocation between two arms, which differs from the recorded single-group trial design; numerical planning values and the observed effect are not available for assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma — NCT00601718.
• Registry record last updated 2017-05-25; status last verified 2017-04.
• Results first posted 2017-05-25.
• 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 University of Washington sponsored this completed phase I/II study, which began in 2007-12 and reached primary completion in 2010-06. Enrollment was 29. The registry describes a single-group regimen of vorinostat, ifosfamide, carboplatin, and etoposide, with rituximab for CD20-positive participants, in people with specified relapsed or refractory lymphoid malignancies or previously untreated T-cell non-Hodgkin lymphoma or mantle cell lymphoma.

The primary outcome is maximum tolerated dose of vorinostat, with a 28-day post-dose timeframe, but its result is not reported in the registry record. Four outcome measures are listed and there are no analysis entries. The safety record reports 10 participants affected by serious adverse events and 25 affected by other adverse events, among 29 at risk for each category. A death count is not reported. The single-group design does not provide a randomized treatment comparison.