FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NCT00383565), a na phase 2 study. The primary outcome is Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment.

2. Clinical Question

The study asked whether treatment with FR901228 was followed by an objective response in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma. The primary outcome was the overall objective response rate, defined in the registry title as complete response or partial response after 6 courses of treatment. The specified assessment timeframe was 24 weeks, corresponding to 6 courses of 4 week cycles.

The registry describes the response criteria as those of the International Working Group for non-Hodgkin's lymphoma. Complete response required disappearance of detectable clinical or radiographic disease and disease-related symptoms, together with normalization of relevant biochemical abnormalities. Partial response required a decrease in the sum of products of greatest diameters of selected dominant nodes or nodal masses, without decrease in the size of other nodes, liver, or spleen. The record's detailed criterion specifies a decrease of at least 50%.

This was a single-group study rather than a randomized comparison. Its primary question was therefore about the number of participants meeting response criteria after treatment, not whether FR901228 performed better than another treatment or control. The registry record does not report the primary response count or rate, nor an analysis of that outcome. It also names median progression-free survival and median overall survival as secondary outcomes, but does not report their estimates. Consequently, the clinical question is identifiable, but the posted record does not provide the outcome results needed to answer it.

3. Trial Design

This was a phase II study sponsored by the National Cancer Institute (NCI). The registry lists an enrollment of 9 and describes the design as single group, with no allocation and no masking. Its title identifies patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma; the listed conditions are recurrent adult diffuse large cell lymphoma and recurrent mantle cell lymphoma. The study status is terminated.

The intervention is listed as romidepsin, while the treatment description uses the name FR901228. Participants in the listed arm were to receive FR901228 intravenously over 4 hours on days 1, 8, and 15. The primary outcome was scheduled for assessment after 6 courses, with a timeframe of 24 weeks. The registry does not explain why the study was terminated, and the reason is not reported in the registry record.

The design has no concurrent control arm in the registry description. As a result, the study can describe outcomes recorded among treated participants, but it does not provide a like-for-like comparison with an untreated group or another therapy. The absence of masking also means that treatment and outcome assessment were not described as blinded. The record does not report further details about response-assessment procedures or safeguards against assessment bias.

Progression-free survival and overall survival are named as secondary outcomes. The record does not report their results, analysis methods, or the populations used for those analyses. It lists 3 outcome measures and 0 analyses. Those registry entries do not supply an efficacy estimate or a statistical comparison. The record also does not report the planned sample-size rationale, a statistical analysis plan, or whether any interim review was planned.

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 Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment, measured over 24 weeks (6 courses of 4 week cycles).

The primary endpoint was overall objective response, combining complete response and partial response after 6 courses of treatment. It was expressed as a count of participants, with the response assessment scheduled for 24 weeks (6 courses of 4 week cycles). In general, an objective response endpoint translates disease assessments into a defined classification: a participant either meets the stated response criteria or does not. Combining complete and partial response gives a summary of participants who meet either category, rather than treating the categories as separate primary outcomes.

The registry's complete-response definition requires disappearance of detectable clinical or radiographic evidence of disease and disease-related symptoms, and normalization of relevant biochemical abnormalities. Partial response is based on a decrease in the sum of products of greatest diameters for selected dominant nodes or nodal masses, alongside specified conditions for other nodes, liver, and spleen. These criteria make the outcome more explicit than an informal judgment that a participant improved.

Response is used in clinical trials as a measure of tumor change during a specified assessment period. It is not interchangeable with progression-free survival or overall survival: those are separate time-to-event outcomes, and the registry lists both as secondary outcomes. The primary endpoint's observed count and rate are not reported in the registry record. Without them, the response criteria can be described, but the degree of response in this study cannot be estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the registry does and does not establish. The explanations below are general; they do not imply that the methods were used in this study. The registry record lists no analyses and does not report a statistical analysis plan, so the actual inferential approach cannot be reconstructed from the posted information.

What does a single-group design estimate?

In general, a single-group trial describes outcomes among participants who receive the study intervention. For a binary endpoint such as objective response, the basic result is a count of participants meeting the response definition, often accompanied by a rate using an analysis denominator. A comparison claim requires a suitable reference. Without a concurrent control group, a response estimate describes the treated group but does not by itself quantify what would have happened under another treatment or without the study intervention.

This distinction matters for interpretation. An outcome can be observed after treatment without proving that treatment caused it. Changes in disease, participant characteristics, assessment practices, and other influences may contribute to the observed result. Random allocation can help balance measured and unmeasured influences between groups, but this registry record describes no allocation and no comparator. It is therefore not a randomized treatment comparison.

What do response counts and rates mean?

A response count is the number of participants classified as having complete or partial response under the stated criteria. A response rate relates that count to a defined denominator. The denominator is important: it may be all enrolled participants or a prespecified analysis population, depending on the trial's plan and reporting. The registry gives an enrollment of 9, but does not report a primary response count, a response rate, or the endpoint analysis denominator. No rate can therefore be interpreted from the record.

In general, binary outcomes simplify a more detailed clinical assessment into categories. That can make the endpoint easier to communicate, but it also means that the definitions and assessment timing matter. The record specifies a response framework and a timeframe after 6 courses. It does not report whether assessments were independently reviewed, how missing assessments were classified, or whether the timing varied in practice.

How should uncertainty be described?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and conveys the uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, though interpretation also depends on the design, assumptions, and quality of the data. A p-value, when used, summarizes how incompatible the data are with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true.

Neither confidence intervals nor p-values for the primary response are reported in the registry record. No inferential result should be inferred from the enrollment or from the absence of an analysis entry. An estimate without a measure of uncertainty would also be difficult to interpret, particularly in a small study. Here, even the observed response estimate is unavailable.

Why does the missing analysis plan matter?

A statistical analysis plan ordinarily specifies how outcomes will be analyzed, how analysis populations will be defined, how missing observations will be handled, and what inferential procedures will be used. Those choices affect the meaning of a reported result. For example, excluding participants without an assessable response can produce a different rate from classifying all enrolled participants according to a prespecified rule. The registry record does not report these choices, so it is not possible to assess whether the analysis followed a stated plan or how sensitive results might be to alternative choices.

The record lists 3 outcome measures and 0 analyses. It also names progression-free survival and overall survival as secondary outcomes, without reporting estimates or methods. Time-to-event analyses generally need a definition of the event, a way to handle participants who have not had the event by the end of follow-up, and information about follow-up. Those details are not reported in the registry record. The survival outcomes therefore cannot be reconstructed from their names alone.

What is the role of planning calculations?

In general, sample-size planning asks how much information a future study might need to detect a chosen effect under stated assumptions. A planning illustration is not an observed result, and it is not observed power. Its interpretation depends on the assumed effect, significance level, allocation, statistical approximation, and endpoint type. The registry record does not report the study's own sample-size justification or statistical plan. The trial itself is single group; any two-arm planning assumptions would describe a hypothetical design calculation, not the design used in this study.

Planning calculations based on an observed effect also inherit the uncertainty of that effect. They should not be treated as proof that a future study will have a specified result, nor as evidence that the current study was adequately powered. Since the registry does not report the primary outcome estimate, there is no reported response effect to interpret as the basis for planning. No design conclusion about adequacy can be drawn from the enrollment alone.

These general principles underline the main statistical constraint: a study question and outcome definition are not themselves results. The record gives enough detail to identify the intended response measure and its timing, but it does not provide the data summary or analysis needed to estimate that response.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, subgroups, or hypotheses. In general, making more statistical comparisons can increase the chance of a seemingly notable result arising by chance if each is judged separately. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory outcomes can help readers interpret multiple results. This is general statistical context, not a description of methods used in this study.

The registry identifies overall objective response as the primary outcome and lists median progression-free survival and median overall survival as secondary outcomes. It lists 3 outcome measures and 0 analyses. The record does not report whether additional endpoints or subgroup analyses were planned, whether multiplicity was addressed, or which outcomes would have been considered confirmatory. These details are not reported in the registry record.

Missing-data handling is also not described. The record does not state how participants with an unevaluable response, incomplete follow-up, or missing survival information were treated. It does not report the number contributing to each analysis or describe an analysis population. The enrolled group size alone cannot identify the endpoint denominator, because the record does not say whether all enrolled participants were assessed for the primary outcome.

In general, missing outcome data can affect both the estimate and its interpretation, especially when the reasons for missingness are related to prognosis or response. A complete-case result, an all-enrolled result, and a result using an imputation method may answer different questions. No such approach can be attributed to this trial from the registry record. The outcome values and missing-data procedures are not reported in the registry record, so neither the extent nor the likely direction of any missing-data influence can be evaluated.

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: thrombocytopenia (22.2%), neutropenia (11.1%), dysphagia (11.1%), glucose, serum-high (11.1%), infection (11.1%).

The registry safety fields list 9 participants at risk for serious adverse events and 6 affected. For other adverse events, it lists 9 at risk and 9 affected. These are participant-level counts in the registry fields; they do not indicate how many separate event episodes occurred. The record also lists serious adverse-event terms with percentages: thrombocytopenia, 22.2%; neutropenia, 11.1%; dysphagia, 11.1%; glucose, serum-high, 11.1%; infection, 11.1%; and diplopia, 11.1%.

These entries should be read as safety reporting, not as proof of causation. The registry does not state in these fields that each event was caused by treatment, and the percentages do not establish comparative risk because no control group is described. The record does not explain the event-collection window, severity grading beyond the serious-event classification, or whether participants could have more than one listed event. Deaths are not reported in the registry field; that should not be interpreted as a count of zero.

Serious adverse events and other adverse events are separate reporting categories. Their counts should not be added, since the record does not clarify overlap between the categories. The safety entries provide a limited description of events recorded in this group, rather than a complete comparative assessment of harms.

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

The record establishes that a phase II, single-group study was conducted for FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma. It identifies the intervention schedule and defines an intended primary response assessment after 6 courses. It also records some adverse-event information and names progression-free survival and overall survival as secondary outcomes.

It does not establish the primary response result. The response count, response rate, and uncertainty around any estimate are not reported in the registry record. The secondary survival results are also not reported. Without those outcome data, readers cannot determine the response observed in the study, the duration of disease control, or survival outcomes from this record.

Even a reported response result from a single-group study would describe outcomes among treated participants, not a randomized contrast against another treatment. The lack of allocation and a control group limits causal interpretation. In addition, the registry does not describe the response analysis population, missing-data rules, or outcome-assessment safeguards. Those omissions make it harder to assess who contributed to the results and how robust an estimate would be.

The safety counts and listed event terms indicate that adverse events were recorded, but they do not establish that the intervention caused those events or how risk compares with another treatment. The safety information is also limited by the absence of further reporting details in the record.

Accordingly, the defensible conclusion is about the registry record's scope, not treatment benefit: it documents a study question and some design and safety information, while leaving efficacy and survival outcomes unavailable. The absence of a reported result is not a negative result, and it is not evidence of no response or no survival events.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a clearly described clinical question and a result that can be interpreted. The registry specifies a phase II, single-group design, an intervention schedule, a primary response endpoint, and an assessment timeframe. Those details tell readers what investigators intended to measure. They do not, by themselves, show what happened to participants.

The distinction is especially important for a binary endpoint. A response count and its denominator are needed to calculate and interpret a rate; a measure of uncertainty is needed to understand its precision. The record gives an enrollment of 9 but does not report the primary response count, rate, analysis denominator, or confidence interval. The intended endpoint is therefore identifiable, but its statistical result is not.

The design also makes comparison a central issue. A single group can provide descriptive information, but without a control group it cannot provide a randomized estimate of the difference between treatments. This limits the type of claim that the design could support, even if the outcome results were reported. The absence of masking is another design feature relevant to assessment, though the record does not describe how response evaluations were conducted.

Finally, the listed secondary outcomes and safety entries show why complete reporting matters across different domains. Survival outcomes require their own estimates and follow-up information; adverse-event counts require context about definitions and collection. Here, the registry names survival outcomes but gives no results, and records safety counts without a comparative group. The study is a useful example of why transparent outcome reporting, analysis details, and design context are all needed before statistical findings can be weighed.

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 is that the registry record does not report the primary response result. No count, rate, or uncertainty interval is available, so the central efficacy endpoint cannot be summarized quantitatively. The named secondary outcomes, median progression-free survival and median overall survival, also have no reported estimates. The record lists 0 analyses, leaving no statistical results to evaluate.

The study is described as single group, with no allocation and no masking. It has no like-for-like control comparison in the registry record, which limits causal conclusions and comparison with other treatments. The reason for termination is not reported in the registry record, and no conclusion should be drawn about why the study ended.

The record does not report the primary endpoint analysis denominator, analysis population, or how missing or unevaluable response assessments were handled. It also does not describe response-review procedures, follow-up completeness, or the statistical plan. These missing details prevent assessment of potential bias, the handling of incomplete data, and the robustness of any estimate.

Safety information is limited to the reported participant counts and listed serious-event terms. The record does not provide the event-collection window or enough detail to establish attribution, overlap between safety categories, or comparative risk. Deaths are not reported in the relevant field, which cannot be treated as a zero count. The enrollment of 9 further means that any estimate, if reported, would need careful attention to uncertainty; the record does not provide the estimate needed to quantify that uncertainty.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma — NCT00383565.
• Registry record last updated 2014-05-20; status last verified 2013-04.
• Results first posted 2012-08-22.
• 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 describes a phase II, terminated, single-group study sponsored by the National Cancer Institute (NCI), with an enrollment of 9. It concerns FR901228, also named romidepsin, in relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma. The listed regimen was intravenous treatment over 4 hours on days 1, 8, and 15.

The primary outcome was overall objective response, defined as complete or partial response after 6 courses, with an assessment timeframe of 24 weeks. Median progression-free survival and median overall survival were listed as secondary outcomes. The registry record does not report results for these outcomes and lists 0 analyses.

Safety entries list 6 participants affected by serious adverse events among 9 at risk and 9 affected by other adverse events among 9 at risk, alongside serious-event terms and percentages. The record does not report the primary efficacy result, survival estimates, analysis populations, missing-data methods, or reason for termination. It supports a description of the study design and recorded safety fields, but not an efficacy or survival conclusion.