This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase 0/1 Biomarker and Pharmacodynamic Study of Roflumilast in Patients With Advanced B-Cell Hematologic Malignancies (CTRC# 13-0013) (NCT01888952), a na early/phase 1 study. The primary outcome is Total Number of Adverse Events..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01888952 |
| Phase | EARLY/Phase 1 |
| Condition | Advanced B-cell Lymphoid Malignancies |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Anand B. Karnad |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced B-cell lymphoid malignancies who had failed at least one prior therapy and for whom no standard curative therapy existed. The conditions listed include CLL, SLL, ALL, MM, WM, mantle cell lymphoma, follicular lymphoma, and DLBCL. The record describes advanced disease as resistant or refractory to standard chemotherapy or biological therapies.
Intervention
Roflumilast was administered orally at 500 mcg daily for 21 consecutive days in a cycle. Prednisone was also used. In Cycle 1, the stated dose was 60 mg/m2, up to a maximum of 100 mg orally daily on Days 8 through 14, at the same time as roflumilast. The Cycle 2 and later prednisone instructions are incomplete in the registry record.
Comparator
There was no separate comparator group. The study is described as non-randomized, open-label, and single-group. It therefore does not provide a randomized comparison of roflumilast and prednisone against another treatment or against either drug alone.
Primary question
The primary outcome measure was the total number of adverse events over an average of 21 days, with adverse events listed by CTCAE Version 4.03 toxicity grade. The registry record does not report a numerical result for that endpoint. Its adverse-event summary separately reports how many participants were affected by serious and other adverse events.
In practical terms, the study was designed to examine biomarker and pharmacodynamic questions alongside safety in a group with advanced disease. Its structure is exploratory: there is no control arm against which to separate treatment-related changes from disease course, prior treatment, or other influences. The listed intervention combines roflumilast with prednisone, so outcomes cannot be attributed to either drug individually using this design. The record identifies the intended population and treatment schedule, but does not report the biomarker results, pharmacodynamic results, or a treatment-effect comparison. The posted safety figures should therefore be read as descriptive observations from this group, not as evidence of comparative benefit or risk.
3. Trial Design
This was a Phase 0/1, open-label, non-randomized, single-group study. The registry lists an enrollment of 10 and marks allocation as not applicable. No masking was used. These features describe a small exploratory study rather than a randomized controlled trial: participants were not assigned between competing treatment groups, and there was no masked assessment specified in the record.
The study population included people with advanced B-cell lymphoid malignancies. The registry lists several disease types, including CLL, SLL, ALL, MM, WM, mantle cell lymphoma, follicular lymphoma, and DLBCL. Participants were described as having failed at least one prior therapy, with no standard curative therapy available. The record also characterizes advanced-stage disease as resistant or refractory to standard chemotherapy or biological therapies. Further eligibility criteria and the detailed recruitment process are not reported in the registry record.
The intervention group is named Roflumilast and Prednisone. Roflumilast was scheduled at 500 mcg orally each day for 21 consecutive days, described as a 21-day cycle. During Cycle 1, prednisone was scheduled at 60 mg/m2, up to a maximum of 100 mg orally daily, on Days 8 through 14 alongside roflumilast. The description for Cycle 2 and subsequent cycles ends before the complete prednisone instructions are given; the remaining schedule is not reported in the registry record.
The study start is listed as 2013-07, primary completion as 2015-01, and status as completed. These administrative milestones do not establish when each participant began or finished treatment. The number of treatment cycles received, treatment duration by participant, and handling of dose changes or discontinuations are not reported in the registry record. Nor does the design information specify a sample-size justification, an interim-analysis plan, or a detailed statistical analysis plan.
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
| Stage | Roflumilast and Prednisone |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Roflumilast and Prednisone |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 |
| Age, Categorical: >=65 years | Participants | 5 |
| Gender: Female | Participants | 6 |
| Gender: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Total Number of Adverse Events., measured over Average of 21 days..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse events |
| Endpoint classification | not reduced to a single comparison |
The registered primary outcome was the total number of adverse events, with an average timeframe of 21 days. The registry states that adverse events were listed using CTCAE Version 4.03 toxicity grade. This endpoint concerns adverse-event counts, which are conceptually different from a count of participants who experienced at least one event. A participant can experience more than one event, so an event total and the number of affected participants are not interchangeable.
In general, collecting adverse events by toxicity grade helps describe the types and severity of unwanted events observed during a study. Counting events can also describe the overall burden recorded during a specified observation period. Those summaries require clear definitions of what qualifies as an event, how events are graded, and what observation time is included. The record identifies the grading system and average timeframe but does not report further counting rules or the numerical primary-endpoint result.
The adverse-event summary includes separate participant counts for serious and other adverse events. Those figures should not be treated as the result for the primary endpoint: they describe affected participants, not the total number of events. The record also does not report biomarker or pharmacodynamic outcome values, despite those topics being part of the study description.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes 10 participants in a single group receiving roflumilast and prednisone. For serious adverse events, the summary lists 10 participants at risk and 0 affected. For other adverse events, it lists 10 at risk and 2 affected. These are descriptive participant counts. They do not state how many individual adverse events occurred, and they do not provide a comparison with an untreated or alternative-treatment group.
The registered primary endpoint is the total number of adverse events over an average of 21 days, with events listed by CTCAE Version 4.03 toxicity grade. A numerical result for this endpoint is not reported in the registry record. The serious and other event summaries cannot fill that gap because the number of participants affected is not the same measure as the total number of events. The record lists no top serious-event terms, so it does not identify specific serious-event types in that summary.
The absence of a serious event among the 10 participants in the posted summary is a description of these observations, not proof that serious events cannot occur. Likewise, the other-event count describes what was recorded in this group; it does not establish a comparative rate or identify which drug, disease, or other factor was responsible. The open-label, single-group design cannot isolate treatment effects from other influences, and the record does not report an analysis that adjusts for them.
No analysis results are reported in the registry record. In particular, it does not provide a confidence interval, hypothesis test, model-based estimate, or numerical biomarker or pharmacodynamic result. Without an interval or other uncertainty estimate, the precision of the participant counts cannot be quantified from the posted results. In general, confidence intervals communicate the range of values compatible with a statistical estimate under the method used; they do not resolve limitations caused by the study design or missing outcome information.
Overall, the posted safety summary supports only a narrow descriptive reading: no participants are listed as affected by serious adverse events, and 2 participants are listed as affected by other adverse events. The primary event-count result, event-level details, and comparative evidence are not reported. These limitations mean that the record cannot answer whether the regimen changes risk relative to another treatment, nor can it establish a treatment effect on the malignancies.
9. Statistical Methods Explained
The registry identifies this as a single-group study, with allocation marked not applicable and no masking. Those design details determine what kinds of statistical conclusions are available. A randomized comparison can estimate differences between assigned groups under its design assumptions. A single-group study instead describes outcomes observed in participants who received the listed regimen; it does not directly estimate how those outcomes would compare with a different treatment or with no treatment.
What does the primary outcome count?
The primary outcome is described as the total number of adverse events over an average of 21 days, with toxicity grade recorded using CTCAE Version 4.03. In general, count outcomes record how many events occur, while participant-level outcomes record whether a person experienced an event. Those measures answer different questions. If one participant has multiple events, an event count may include each event, whereas an affected-participant count records that participant as affected. The registry's safety summary reports affected participants for serious and other adverse events, but does not report the numerical total for the primary event-count endpoint.
Count data may vary more than a simple statistical model expects, particularly when events cluster in some participants or when participants have different observation times. In general, over-dispersion means that the observed variability is greater than assumed by a basic count model. A model that ignores this can give uncertainty estimates that are too narrow. The record does not report a count model, a method for assessing over-dispersion, or a model-based endpoint analysis, so no such method should be attributed to this study.
What do the safety counts mean?
The serious-event summary lists 10 participants at risk and 0 affected; the other-event summary lists 10 at risk and 2 affected. These figures are participant counts, not event totals. They do not identify whether one affected participant had multiple events, provide event-level timing, or show how long each participant was observed. The primary endpoint's average 21-day timeframe does not, by itself, establish equal follow-up for every participant. Details about individual observation periods are not reported in the registry record.
In general, an estimate accompanied by a confidence interval communicates both its size and its statistical uncertainty. A hypothesis test addresses compatibility with a specified null model, while a confidence interval gives a range of estimates under the chosen method. Neither can be reconstructed from the posted participant counts without further assumptions and outcome information. No confidence intervals or hypothesis-test results are reported, and an unadjusted re-calculation is not available from the posted summary because the primary event-count result is absent.
How should planning calculations be read?
The planning illustrations are explicitly based on assumptions rather than the study's own design. Their stated framework uses a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations refer to participants per arm; time-to-event illustrations refer to the total number of events. These assumptions are not evidence that this study randomized participants between two arms, and they are not observed power.
In general, sample-size planning asks how much information a future design might need to detect a chosen effect under specified assumptions. The result depends on the assumed effect, variability, allocation, and analysis method. A planning illustration cannot establish the probability that a completed study detected an effect, and it cannot replace a design-specific justification. Here, the record does not report the trial's own sample-size justification, and the study itself is single-group. The hypothetical two-arm framework therefore should not be read as a feature of the actual trial.
The registry lists one outcome measure and no analysis results. It does not report a detailed statistical plan, a method for handling repeated events, a missing-data approach, or a defined analysis population. Those omissions matter because statistical results depend not only on the outcome definition but also on how observations are counted, how incomplete follow-up is handled, and which participants are included. General statistical explanations clarify these issues but cannot supply the methods or results absent from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure, the total number of adverse events, but does not report a multiplicity plan. In general, multiplicity arises when several outcomes, comparisons, subgroups, or repeated tests are assessed; without an appropriate plan, the chance of a chance-positive result can increase. The record does not describe whether biomarker or pharmacodynamic measures were analyzed as additional outcomes, how any such analyses were prioritized, or whether adjustments for multiple testing were used. Their numerical results are not reported in the registry record.
Missing-data methods are not reported. The record does not state how incomplete adverse-event observations, missed visits, early treatment discontinuations, or participants with limited follow-up were handled. It also does not report whether every enrolled participant contributed to every analysis. The population field for the primary outcome is blank, so the outcome-specific analysis population is not specified. These details are important because incomplete observation can affect both event counts and the interpretation of participant-level safety summaries.
No detailed analysis plan, interim-analysis plan, or inferential analysis is reported. It is therefore not possible to determine whether there were prespecified subgroup analyses, repeated assessments, or rules for selecting among analyses. The absence of these details should not be filled in by assumption. In general, prespecification helps readers distinguish planned analyses from exploratory ones, while transparent missing-data reporting clarifies who contributed information and for what period. Neither can be evaluated from the registry information available.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Roflumilast and Prednisone | 0 | 10 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Roflumilast and Prednisone | 2 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Roflumilast and Prednisone |
|---|---|---|
| Fatigue | General disorders | 2 of 10 |
The registry lists 10 participants at risk for serious adverse events, with 0 affected. For other adverse events, it lists 10 at risk and 2 affected. Read these as numbers of participants recorded as affected in each category, not as counts of individual events. The primary outcome, by contrast, is defined as a total number of adverse events, and its numerical result is not reported in the registry record.
The serious-event summary gives no top serious-event terms. That means the posted summary does not identify specific serious-event types; it should not be read as a detailed event listing. The record also does not report event timing, duration, severity distributions, attribution to a particular drug, or individual participant follow-up. The figures cannot establish whether an event was caused by roflumilast, prednisone, the underlying malignancy, or another factor.
In general, safety counts describe observations in the population and timeframe captured; they do not establish what would happen in a larger or different population. Here, the single-group design offers no treatment comparison, and the limited event summary does not include uncertainty estimates. The numbers should therefore be interpreted descriptively, without treating them as comparative risk estimates or a complete account of all adverse-event details.
12. What the Result Does, and Does Not, Mean
The posted results describe a small, single-group experience with roflumilast and prednisone in people with advanced B-cell malignancies. The safety summary records no participants affected by serious adverse events and 2 participants affected by other adverse events among 10 participants at risk in each category. These are useful descriptive details about the registry summary, but they do not provide the primary outcome's total adverse-event count.
The study's title and summary identify biomarker and pharmacodynamic aims, but the registry record does not report numerical findings for those aims. It also does not report a numerical primary-endpoint result, confidence intervals, or inferential tests. Consequently, the posted information does not establish a biomarker change, a pharmacodynamic effect, or a comparative treatment effect. It does not establish whether the regimen is more or less effective or safe than another option.
In general, a single-group exploratory study can document what was observed under a particular regimen and can contribute descriptive information. Without a comparator, however, changes over time cannot be confidently attributed to treatment rather than disease course, prior therapy, or other influences. Without detailed outcome data and uncertainty estimates, the precision and completeness of the observed safety summary also cannot be assessed.
The posted results do not mean that no adverse events occurred: 2 participants are listed as affected by other adverse events. Nor does a serious-event count of 0 among the participants summarized establish that serious events are impossible. The appropriate interpretation is limited to what the registry records: participant-level safety counts for this group, with the primary event-count result and other study aims not numerically reported.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between a registered endpoint and a posted result. The primary outcome is defined as the total number of adverse events over an average of 21 days, but the record does not give that total. It separately reports participant counts for serious and other adverse events. Because event counts and affected-participant counts answer different questions, those safety figures cannot substitute for the missing primary-endpoint result.
The single-group design is also important. It can describe what was recorded among participants receiving the combined regimen, but it cannot provide a randomized comparison or isolate the contribution of either drug. The study's exploratory biomarker and pharmacodynamic aims make complete reporting particularly relevant: without numerical results and analysis details, readers cannot assess the magnitude or uncertainty of findings for those aims.
The planning illustrations use a hypothetical two-arm framework, even though the actual study is non-randomized and single-group. Keeping design assumptions separate from observed trial structure prevents a planning calculation from being mistaken for observed power or a feature of the trial. More broadly, the record shows why interpretation depends on matching the measure, population, and design to the statistical claim. Here, only a limited descriptive safety summary is available for interpretation.
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 limitations are specific to interpreting this record. The enrollment is 10, and the study has a single group without randomization or masking. The posted adverse-event figures are participant counts, while the primary endpoint is an event count; the primary endpoint's numerical result is not reported. This prevents direct interpretation of the registered primary measure and limits assessment of event frequency or grade.
The registry does not provide event-level listings, event timing, duration, participant-level follow-up, attribution, or a distribution of toxicity grades. It also does not report numerical biomarker or pharmacodynamic findings, even though those topics are part of the study description. No confidence intervals or statistical analyses are reported, so the precision of the observed safety counts and the uncertainty around any outcome estimate cannot be assessed from the record.
The combined regimen prevents separation of outcomes associated with roflumilast from those associated with prednisone. The absence of a comparator also limits interpretation of outcomes relative to another treatment or to the expected course of disease. The Cycle 2 and subsequent prednisone instructions are incomplete in the registry record, and details of actual treatment exposure, discontinuations, and follow-up are not reported.
Finally, eligibility details beyond the broad disease and prior-therapy description, the analysis population, missing-data methods, multiplicity handling, sample-size justification, and interim-analysis plan are not reported. These gaps restrict assessment of selection, completeness, and analytic choices. They do not prove that such procedures were absent; they mean the registry record does not describe them.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 0/1 Biomarker and Pharmacodynamic Study of Roflumilast in Patients With Advanced B-Cell Hematologic Malignancies (CTRC# 13-0013) — NCT01888952.
- Registry record last updated 2017-02-27; status last verified 2017-01.
- Results first posted 2017-02-27.
- 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.
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18. Record Summary
The record describes a completed Phase 0/1, open-label, non-randomized, single-group study of roflumilast and prednisone in advanced B-cell lymphoid malignancies. Enrollment was 10. Roflumilast was scheduled orally at 500 mcg daily for 21 consecutive days; the Cycle 1 prednisone schedule is listed, while later-cycle instructions are incomplete.
The primary outcome was the total number of adverse events over an average of 21 days, listed by CTCAE Version 4.03 toxicity grade. Its numerical result is not reported in the registry record. The safety summary lists 0 of 10 participants affected by serious adverse events and 2 of 10 affected by other adverse events. No top serious-event terms are listed, and no analysis results are reported.
The study is exploratory and has no comparator group. Numerical biomarker and pharmacodynamic results, statistical analysis details, missing-data methods, and the trial's own sample-size justification are not reported in the registry record.