SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma (NCT00787527), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicity for Determination Phase I (Schedule A) MTD of Vorinostat.

2. Clinical Question

3. Trial Design

NCT00787527 is registered as a phase I/II, single-group study of vorinostat plus CHOP in untreated T-cell non-Hodgkin's lymphoma. M.D. Anderson Cancer Center is listed as the sponsor. The registry gives a start date of 2008-11, a primary completion date of 2012-12, and a status of completed. Enrollment is recorded as 14 participants. The record does not state how many participants entered each phase.

The design is open-label: masking is listed as none. Allocation is not applicable, consistent with the single-group classification. The registry describes one treatment combination, Zolinza plus CHOP, while the safety record divides participants by dosing schedule. Schedule A is titled as vorinostat once or twice daily; Schedule B is titled as vorinostat three times daily. This schedule-based safety presentation does not turn the study into a randomized comparison. The record does not describe assignment procedures between schedules.

The phase I component escalated vorinostat doses in successive 3+3 cohorts. For Schedule A, the registry describes oral vorinostat on days 5 to 14 during each 21-day cycle, beginning at 300 mg once daily and then using 200 mg twice daily. The endpoint description states that dose escalation was intended to identify the maximum tolerated dose under a specified dose-limiting toxicity rule. The brief summary also says that the study aimed to assess the combination's safety and how well it worked. The registry record does not provide detailed phase II methods, follow-up procedures, or a separate phase II analysis plan.

Because there is no randomized control group, this design can describe outcomes among participants receiving the combination and support the recorded dose-finding process. It cannot, by itself, separate treatment effects from other explanations for observed outcomes or provide a controlled estimate of comparative benefit.

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 Number of Participants With Dose Limiting Toxicity for Determination Phase I (Schedule A) MTD of Vorinostat, measured over 21 Days.

The primary endpoint is titled as the number of participants with dose-limiting toxicity for determination of the Schedule A maximum tolerated dose of vorinostat. It is a participant count: the endpoint concerns how many people meet the study's dose-limiting toxicity definition, rather than the total number of toxicity episodes. The specified assessment period is 21 Days. The description says that dose-limiting toxicity was assessed continually during each 21-day cycle.

The endpoint is used in a dose-finding process. The registry defines the maximum tolerated dose as the highest dose level at which 6 patients have been treated with fewer than 2 instances of dose-limiting toxicity. Participants were entered in successive 3+3 cohorts while the vorinostat dose was escalated. Under this approach, toxicity observations inform whether the next cohort receives a higher dose or the dose level is considered the maximum tolerated dose.

For Schedule A, oral vorinostat was given on days 5 to 14. The described starting dose was 300 mg once daily, with total doses of 3000 mg over 10 days per cycle; the next described dose was 200 mg twice daily, with total doses of 4000 mg over 10 days per cycle. These are elements of the registered endpoint description, not evidence that a particular dose was established. The observed dose-limiting toxicity count and the maximum tolerated dose are not reported in the registry record. Without those results, the endpoint definition can be explained, but the dose-finding outcome cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are most useful when linked to the question the trial was designed to answer. This registry describes a phase I/II study, but the recorded primary outcome is specifically a dose-finding measure: the number of participants with dose-limiting toxicity for determination of the Schedule A maximum tolerated dose. It is not a comparative effect estimate between randomized groups. The posted record includes the endpoint definition and selected safety summaries, but does not report an analysis estimate for the primary endpoint.

What does a participant count measure?

A participant count records how many people experienced an event meeting the endpoint definition. In this study, the event is dose-limiting toxicity. Counting participants differs from counting every occurrence: one person could experience more than one toxicity episode, while the primary outcome is worded as a number of participants. The registry's endpoint definition supplies a rule for using observed toxicity in dose escalation. The number of participants meeting that rule at each dose level is not reported in the registry record, so the actual decision path cannot be reconstructed from the posted information.

For this kind of count, context matters. The number treated at each dose, observation time, event definition, and completeness of follow-up all affect interpretation. The registry describes continual reassessment during each 21-day cycle and gives the Schedule A dosing days, but does not report the observed participant counts by dose level. It also does not provide a confidence interval or other precision measure for the primary outcome. A confidence interval, in general, expresses uncertainty around an estimate; it does not replace the underlying observed data or correct for incomplete reporting.

How does the dose-escalation rule work?

The registry describes dose escalation in successive 3+3 cohorts. In general, a cohort-based dose-finding design observes toxicity at a dose before deciding whether to enroll a later cohort at a higher dose, continue at the same dose, or stop escalation. Here, the stated maximum tolerated dose criterion is the highest dose level at which 6 patients have been treated with fewer than 2 instances of dose-limiting toxicity. The record also describes continual assessment within each 21-day cycle. These details define the intended decision rule, but they do not show which branch of the rule occurred in practice. The actual cohort-level results and final dose decision are not reported in the registry record.

The dose details belong to the endpoint description: Schedule A used oral vorinostat on days 5 to 14, starting at 300 mg once daily and then moving to 200 mg twice daily. The stated total doses were 3000 mg over 10 days per cycle and 4000 mg over 10 days per cycle, respectively. These protocol details do not reveal the number of participants treated at each level or the toxicity observed at each level. Schedule B is described in the safety grouping as three times daily, but its dose amount and detailed administration schedule are not reported in the registry record.

What can safety summaries establish?

The serious adverse event figures are counts of affected participants relative to the recorded group sizes, as labeled in the registry. They are useful as descriptive safety information for these enrolled groups. They do not identify a causal treatment effect, because the study is single-group and the schedule categories are not described as randomized control groups. Serious adverse events are also distinct from the primary dose-limiting toxicity endpoint: the registry does not state that every serious adverse event met the dose-limiting toxicity definition, nor that every dose-limiting toxicity was a serious adverse event.

The registry lists selected serious adverse event terms as percentages. Percentages can help describe how often listed terms occurred in the reported safety data, but interpretation also requires clear denominators, event definitions, and information about whether the figures refer to participants or episodes. The term-specific counts and denominator explanation are not reported in the registry record. General statistical caution is warranted when reading percentages from small groups: each observed participant can materially affect a percentage, and a percentage without a clear denominator and uncertainty measure gives limited information about precision.

What do planning calculations mean?

Any sample-size illustrations associated with the registry analysis are planning calculations based on the observed effect, not the trial's own design. The stated calculation assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Those assumptions describe a hypothetical planning exercise, not how this single-group, non-randomized trial was allocated or analyzed. Such illustrations are not observed power and cannot substitute for a reported estimate with its uncertainty. The numerical planning results and the observed primary effect are not reported in the registry record.

In general, a power calculation estimates the sample size needed to detect a prespecified effect under stated assumptions. It does not show that a study actually had a particular probability of finding a result after the data have been collected. It is especially important not to read a hypothetical two-arm calculation as evidence that this study contained a randomized two-arm comparison. The trial record instead describes one treatment combination and dose schedules used in the dose-finding and safety context.

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("Schedule A - Vorinostat Once Daily", "Schedule A - Vorinostat Twice Daily")
n      <- c(6, 2)
events <- c(1, 2)
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  Schedule A - Vorinostat Once Daily  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Schedule A - Vorinostat Twice Daily  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 0 analysis records. These entries describe what is recorded in the registry, but they do not establish whether analyses were conducted elsewhere or whether all analyses were registered. The primary endpoint is identified, while the two other outcome measures and their results are not described in the registry record for this analysis. Statistical methods for combining or prioritizing multiple outcomes are not reported in the registry record.

Multiplicity arises when several outcomes, time points, subgroups, or comparisons are tested. In general, testing multiple questions can increase the chance of at least one apparently unusual result unless the analysis plan accounts for that structure. No multiplicity adjustment or prespecified hierarchy of outcomes is reported in the registry record. With no posted efficacy analysis or primary endpoint result, it is not possible to assess how multiplicity was handled in practice.

Missing-data methods, the analysis population, and rules for handling participants who did not complete toxicity assessment are not reported in the registry record. The enrollment figure does not show how many participants contributed data to each endpoint or how complete follow-up was. These details matter because a participant count can be affected by incomplete observation, particularly when toxicity is assessed over treatment cycles. The registry gives an assessment timeframe and dosing description but does not provide a participant flow or endpoint-specific denominators beyond the safety group figures. Consequently, the completeness and analysis set for the primary outcome cannot be evaluated from the posted record.

12. 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: neutropenia (62.5%), pain (25.0%), thrombocytopenia (25.0%), diarrhoea (16.7%), anaemia (16.7%).

The serious adverse event summary separates participants by schedule. In Schedule A, 8 participants were listed as at risk and 8 as affected. In Schedule B, 6 were listed as at risk and 5 as affected. These are participant-level safety figures as presented in the registry, not counts of every serious event episode. The death figures are not reported in the registry record.

The registry also lists the most frequently recorded serious adverse event terms with percentages: Neutropenia, 62.5%; Pain, 25.0%; Thrombocytopenia, 25.0%; Diarrhoea, 16.7%; Anaemia, 16.7%; and Oral Mucositis, 12.5%. These percentages should be read as descriptive entries, not as comparisons of treatment schedules or as estimates of causal risk. The registry does not give term-specific participant counts or explain the denominator for these percentages in the record.

Serious adverse events and dose-limiting toxicity are not interchangeable concepts. The primary endpoint uses a dose-limiting toxicity definition for dose selection, whereas this safety summary reports serious adverse events. The record does not state which listed serious events met the dose-limiting toxicity definition. The lack of a control group and the small schedule groups also limit comparative interpretation. These figures describe recorded safety experience; they do not by themselves determine whether the combination caused an event or how its risk compares with another treatment.

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

The registry record establishes that a phase I/II study of vorinostat plus CHOP in untreated T-cell non-Hodgkin's lymphoma was completed, enrolled 14 participants, and included a dose-finding question for Schedule A. It defines the primary outcome as the number of participants with dose-limiting toxicity and describes the rule intended to determine the maximum tolerated dose. The record also presents selected serious adverse event information by schedule.

The record does not report the observed primary outcome count, the maximum tolerated dose, or an efficacy estimate. The absence of those results from the registry record cannot be interpreted as a favorable or unfavorable outcome. It also does not indicate that no events occurred. The study's stated aim to learn how well the combination worked is not itself evidence of benefit; an aim and an outcome are different kinds of information.

The safety figures should be interpreted as descriptions of small, schedule-specific groups, not as comparative evidence. The study is registered as single-group, with no randomized control and no masking. Schedule A and Schedule B are not documented as equivalent groups assigned to different treatments under a comparative design. Therefore, apparent differences in their reported figures cannot establish that one schedule is safer or more hazardous than the other.

In general, a precise interpretation of a clinical trial result requires the observed outcome, the number of participants contributing data, and an estimate of uncertainty. The primary result and its precision are not reported in the registry record. Details such as analysis populations, missing-data handling, and the full phase II analysis approach are also unavailable. The appropriate reading is therefore narrow: the posted record describes the treatment, dose-finding rationale, and selected safety findings, while leaving the principal dose-finding result and efficacy question unresolved.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the endpoint must be read together. The registered primary outcome is a participant count used in a phase I dose-finding process, not a comparative efficacy estimate. Its interpretation depends on dose-specific toxicity observations and the stated maximum tolerated dose rule. The registry explains that rule but does not report the outcome count or the dose ultimately selected. Statistical readers should distinguish a clearly defined endpoint from a reported result: the former does not supply the latter.

The record also demonstrates the limits of schedule-based safety summaries. It reports serious adverse events separately for Schedule A and Schedule B, but does not describe randomized assignment between them or identify either as a control. The counts are informative as descriptions of the groups, yet they do not support a causal contrast. This distinction matters whenever readers encounter multiple groups in a trial record: separate labels do not automatically mean the groups form a valid comparative design.

Finally, registry completeness is part of statistical interpretation. The record gives enrollment, design, timing, endpoint definitions, and selected safety data, while leaving key analysis details and primary results unreported. A careful assessment identifies both what the record permits and what remains unknown. That practice prevents the dose-finding plan from being mistaken for its result and prevents safety descriptions from being overstated as comparative or efficacy evidence.

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 primary limitation is that the registry record does not report the primary endpoint result. The dose-limiting toxicity count for Schedule A, dose-level outcomes, and maximum tolerated dose are unavailable. The record therefore cannot show how the stated escalation rule operated or what dose was selected. An endpoint definition alone is insufficient to assess the result or its precision.

The study is single-group and unmasked, with allocation listed as not applicable. There is no randomized control group for estimating comparative effects. Although safety data are separated into Schedule A and Schedule B, the record does not describe randomized assignment or establish that the groups were comparable. Their safety figures should not be used as a controlled comparison.

Enrollment is recorded as 14, but the number contributing to each phase, dose level, and outcome is not reported in the registry record. Participant flow, losses to follow-up, analysis populations, and missing-data methods are also not reported. These omissions make it difficult to determine how complete the outcome information was or how broadly it applies to the enrolled group.

Further detail on the phase II analysis, efficacy results, toxicity grading criteria, protocol deviations, and analysis plan is not reported in the registry record. The serious adverse event term percentages are listed without term-specific counts or a denominator explanation. The study's completion status and stated aims do not resolve these information gaps. The statistical interpretation must remain limited to the design description and the safety figures actually recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma — NCT00787527.
• Registry record last updated 2014-09-09; status last verified 2014-09.
• Results first posted 2014-09-09.
• 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

NCT00787527 is a completed phase I/II, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 14 participants with untreated T-cell non-Hodgkin's lymphoma and evaluated vorinostat with CHOP. The registry records a start date of 2008-11 and a primary completion date of 2012-12, with no masking and no applicable allocation.

The primary endpoint concerns the number of participants with dose-limiting toxicity for Schedule A and the determination of the maximum tolerated dose. The registry describes dose escalation and a 21-day assessment cycle, but the primary endpoint result and selected dose are not reported in the registry record. Serious adverse event figures are listed separately for Schedule A and Schedule B, with selected event terms and percentages. The record does not describe a randomized comparison, and several analysis details, including missing-data methods and analysis populations, are not reported.