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 CC-5013 (Lenalidomide) and Rituximab in Waldenstrom's Macroglobulinemia (NCT00142168), a na phase 2 study. The primary outcome is Time to Progression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00142168 |
| Phase | Phase 2 |
| Condition | Waldenstrom's Macroglobulinemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dana-Farber Cancer Institute |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with Waldenstrom's macroglobulinemia. The primary outcome population is described as all enrolled patients, and the registry record reports an enrollment of 16. Eligibility criteria and further characteristics of enrolled participants are not reported in the registry record.
Intervention
The intended regimen combined CC-5103 (lenalidomide) with rituximab. The record describes 48 weeks of intended therapy, with lenalidomide given for 3 weeks followed by 1 week off, and rituximab scheduled in two periods. The registry title uses CC-5013, while the official title and intervention description use CC-5103; the record does not explain this difference in naming.
Comparator
There was no separate comparator group. The study is classified as single-group, with allocation listed as not applicable and masking listed as none. Consequently, the record does not present a randomized comparison against another treatment or a control condition. Comparisons with other studies or with an assumed untreated course are not part of the reported design.
Primary question
The primary question was how long it took from starting therapy until progression, defined in the record as a 25% increase in serum IgM from nadir. The stated endpoint is time to progression, and its reporting timeframe is listed as 34.3 months. Although the endpoint is described as a median with a full range, the numeric median and range are not reported in the registry record. The record therefore states the intended clinical question and its endpoint definition, but not a quantitative answer to that question.
3. Trial Design
This was a Phase II, single-group study sponsored by Dana-Farber Cancer Institute. The registry record reports 16 enrolled participants and identifies Waldenstrom's macroglobulinemia as the condition under study. Allocation is listed as not applicable, masking as none, and the study model as single group. These classifications describe a design without a randomized control arm and without masking.
The intended treatment combined CC-5103 (lenalidomide) and rituximab. The regimen description specifies 48 weeks of intended therapy: lenalidomide at 25 mg/d for 3 weeks followed by 1 week off, and rituximab at 375 mg/m(2)/wk during weeks 2 to 5 and 13 to 16. These are regimen details, not evidence that every enrolled participant received every planned dose or completed the intended course. Treatment exposure, adherence, dose changes, and reasons for discontinuation are not reported in the registry record.
The registry title names CC-5013 (lenalidomide), whereas the official title and intervention descriptions use CC-5103. The record does not explain the difference, so it cannot establish whether this is a naming convention or a discrepancy in the record. The listed study status is terminated. The reason for termination is not reported in the registry record, and that status alone does not establish why enrollment or follow-up ended.
The record lists a study start of 2004-09 and primary completion of 2006-05. Its stated primary endpoint is time to progression among all enrolled patients. Although major and minor response rates are listed as secondary outcomes, their numeric results are not reported in the registry record. A detailed protocol, eligibility criteria, planned enrollment rationale, and full statistical analysis plan are not reported in the registry record.
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.
Before assignment: Symptomatic WM patients requiring therapy
Overall Study
| Stage | Lenalidomide and Rituximab |
|---|---|
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled patients
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 | Lenalidomide and Rituximab |
|---|---|---|
| Participants analysed | 16 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 |
| Age, Categorical: >=65 years | Participants | 6 |
| Age, Continuous | years | 59 (SD 9) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 12 |
| Region of Enrollment: United States | participants | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Progression, measured over 34.3 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Time to progression measures the duration from starting therapy until a defined progression event. In this study, progression was defined as a 25% increase in serum IgM from nadir. The endpoint is expressed in months and is described as a median with a full range. The listed timeframe is 34.3 months, but the registry record does not explain further what observation window that timeframe represents.
Time-to-event endpoints are used when the timing of an event matters and participants may have different lengths of observation. A median can describe the time by which half of the observed population has experienced the event, provided the data support estimating it. A full range describes the span of observed values; it is not the same as a confidence interval and does not, by itself, quantify uncertainty around the median.
For this endpoint, the registry record gives the measurement definition and the form of the summary, but not the numeric median or full range. It also does not report a confidence interval, event count, censoring details, or a hazard ratio. Without those results, the duration until progression and the precision of its estimate cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable question: time from treatment initiation to progression defined by a specified serum IgM change. It also identifies the endpoint population as all enrolled patients. However, it does not report the numeric primary outcome. The record specifies a median and full range as the intended summary, but neither value is available in the reported result. The timeframe is listed as 34.3 months, which should not be mistaken for the median time to progression or treated as a follow-up estimate without further explanation.
As a result, the registry record does not establish how long participants remained progression-free, how much that duration varied, or how precisely the median was estimated. It gives no confidence interval, event count, or sponsor-reported hazard ratio for the primary endpoint. The number of analyses reported is zero. No p-value or model-based comparison is reported. This is not evidence that the outcome had a particular value or that a statistical test found a particular result; the primary result is simply not reported in the registry record.
The design also constrains what can be concluded. Because this was a single-group study with no separate comparator, any observed outcome would describe the enrolled participants under the study regimen, not a comparative treatment effect against a randomized control group. A before-and-after or historical comparison would require additional assumptions and information that are not reported in the registry record. The single-group design does not by itself show what would have happened to the same participants under another treatment or no treatment.
The planned regimen is described in detail, but intended dosing should not be equated with treatment received. The record does not report completion, adherence, dose modifications, or reasons for stopping treatment. Those details matter when interpreting outcomes because the treatment actually received may differ among participants from the intended schedule.
The record lists 16 enrolled participants. A study of this size can have limited precision for outcome estimates, especially for time-to-event summaries, but no precision measure is reported for the primary endpoint. The size alone is not a substitute for a confidence interval or a reported event count. No sample-size justification is reported in the registry record, and the termination status has no stated reason.
The registry record lists major and minor response rates as secondary outcomes, but provides no numeric values for them. It also lists serious adverse-event information, which describes observed harms in the recorded group rather than providing a randomized safety comparison. These results should be interpreted as descriptive registry entries, with the missing outcome detail and absence of a control group kept in view. The available information supports describing the study design and endpoint, but not estimating the size, direction, or precision of the primary outcome.
9. Statistical Methods Explained
Time to progression is a time-to-event outcome: the measured quantity is the time until a defined event occurs. Here, the event definition is a 25% increase in serum IgM from nadir, and the clock begins at starting therapy. The stated unit is months. This definition is important because a time-to-event result depends on both the recorded time origin and the rule for deciding that the event has occurred.
What does a median time-to-event result describe?
In general, a median time-to-event estimate is the point at which the estimated event-free proportion reaches one half. It summarizes the timing of events without requiring the distribution of times to be symmetric. It is different from an arithmetic mean and is not a claim that every participant experienced the event at that time. Estimating a median may require methods that account for participants whose event status is not observed during their available follow-up.
The registry record says the primary outcome is reported as a median with a full range, but it does not provide the actual median or range. The listed timeframe is 34.3 months; this is not enough to recover either statistic. A range is a description of the span of observations, whereas a confidence interval describes uncertainty in an estimate. They answer different questions. Neither a confidence interval nor the details needed to assess the median's precision are reported in the registry record.
Why do censoring and follow-up matter?
In general, a participant may leave observation or reach the end of follow-up before a progression event is recorded. Such an observation is commonly treated as censored: the event time is known only to exceed the participant's observed time. Time-to-event methods can use this partial information, but their interpretation depends on how censoring is handled and on assumptions about the observation process. The registry record does not report censoring counts, follow-up distributions, or the method used to estimate the endpoint. It is therefore not possible to evaluate those aspects of the analysis from the posted outcome information.
The endpoint definition also makes event ascertainment central. The record defines progression using serum IgM relative to nadir but does not report measurement schedules, confirmation rules, or how missing measurements were handled. These details affect whether and when a progression event can be identified. They are not reported in the registry record and should not be inferred from the general endpoint description.
What can a hazard ratio add?
In general, a hazard ratio compares event rates over time between groups under a specified model. It is a relative measure, not a direct statement of the difference in median times, and its interpretation depends on the comparison and modeling assumptions. This study is classified as single-group, so the record does not identify a randomized comparator for such a contrast. No sponsor-reported hazard ratio or primary-endpoint analysis is reported in the registry record. A hazard ratio should not be imputed from the endpoint label or the study design.
Confidence intervals are generally used to show the range of estimates compatible with the data under a statistical procedure and its assumptions. Their width conveys precision; they do not guarantee that a true value lies in the interval. Because no interval is reported for the primary result, the precision of a median time-to-progression estimate cannot be evaluated. A full range, even if it were available, would not replace that uncertainty measure.
How should planning illustrations be understood?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, the analysis, and the desired error rates or power. It is not a result observed in the study and is not evidence that the study had a particular probability of finding a result. The registry record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the stated convention is to express the planning quantity as a total number of events using the Schoenfeld method; other outcomes are expressed as participants per arm. These are planning assumptions, not the design actually listed for this single-group study.
The record does not provide the numerical planning illustrations or the effect estimate needed to interpret such calculations. Any illustration based on an observed effect would be conditional on that effect and would not be the original trial's design justification. The registry record does not report a sample-size justification, a target effect used in the original design, or an interim-analysis plan. Those elements must not be reconstructed from the enrollment count or from a post hoc planning calculation.
More broadly, a statistical method should be interpreted together with its data, assumptions, and analysis population. Here, the primary population is identified as all enrolled patients, but the analysis method, event count, missing-data approach, and numeric result are not reported in the registry record. Thus the endpoint definition can be explained, but the analysis cannot be independently evaluated or reproduced from the reported information.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists major response rate and minor response rate as secondary outcomes, in addition to the primary time-to-progression endpoint. It does not provide their numerical results or describe how the outcomes were analyzed. The record reports zero analyses. It does not state whether the secondary outcomes were tested formally, whether any tests were prespecified, or how multiple outcomes or repeated tests were handled. A multiplicity adjustment or hierarchy should not be assumed.
Multiplicity matters in general when several outcomes or comparisons are examined: the chance of at least one apparently notable result can increase if each is assessed without an agreed strategy. How that issue applies depends on the analysis plan and the inferential claims. No such plan or adjustment method is reported in the registry record. Because the primary outcome result is also absent, there is no basis for evaluating how primary and secondary findings were interpreted together.
The primary analysis population is described as all enrolled patients. That identifies the intended population label, but does not explain how participants with incomplete observations, early discontinuation, or missing endpoint measurements were handled. The registry record does not report missing-data methods, censoring rules, exclusions from analysis, or the number of participants contributing to each outcome. It also does not report whether analyses followed an intention-to-treat principle or used another population definition. Those distinctions matter because the analyzed group and the handling of unavailable observations can affect estimates.
Interim analyses, stopping rules, and adjustments connected with them are not reported in the registry record. The study status is terminated, but no reason is given; termination alone does not establish that a statistical stopping rule was used. The posted information therefore does not support conclusions about multiplicity control, missing-data assumptions, or the conduct of interim monitoring.
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 |
|---|---|---|---|
| Lenalidomide and Rituximab | 11 | 16 | 68.8% |
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 |
|---|---|
| Lenalidomide and Rituximab | 8 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | Lenalidomide and Rituximab |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 5 of 16 |
| Anemia | Blood and lymphatic system disorders | 1 of 16 |
| arrythmia | Cardiac disorders | 1 of 16 |
| chest pain | Cardiac disorders | 1 of 16 |
| pulmonitis | Respiratory, thoracic and mediastinal disorders | 1 of 16 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 16 |
| pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lenalidomide and Rituximab |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 8 of 16 |
Serious events with the highest arm-level rate: neutropenia (31.2%), anemia (6.2%), arrythmia (6.2%), chest pain (6.2%), pulmonitis (6.2%).
The registry record lists a Lenalidomide and Rituximab group with 16 participants at risk for serious adverse events and 11 affected. It separately lists 16 at risk for other adverse events and 8 affected. These are group-level counts as recorded; they do not describe severity, timing, duration, or whether an affected participant experienced one or multiple events. The record does not provide further definitions or participant-level detail.
The listed serious adverse-event terms include Neutropenia at 31.2%, and Anemia, arrythmia, chest pain, pulmonitis, and Thrombocytopenia at 6.2% each. These percentages are reproduced as registry entries. The record does not report the event counts for each term, clarify whether a participant could appear under multiple terms, or provide a full account of all events. The term is spelled “arrythmia” in the registry record.
These safety figures are descriptive observations in a single-group study. They do not establish that the regimen caused an event, and they do not allow a comparison of risk against a control group. Differences in observation time, reporting, or event definitions cannot be evaluated from the registry record. The count of affected participants should also not be confused with the number of individual events.
12. What the Result Does, and Does Not, Mean
The registry record documents a Phase II, single-group study of intended lenalidomide and rituximab therapy in Waldenstrom's macroglobulinemia, with 16 participants enrolled. It defines time to progression using a serum IgM threshold and identifies all enrolled patients as the primary outcome population. This provides useful information about the question the study set out to address and the planned treatment regimen.
It does not provide a numeric primary endpoint result. Although the result is described as a median with a full range, those values are absent from the registry record. The listed timeframe of 34.3 months does not substitute for the median, range, event count, or follow-up distribution. Without those quantities or a confidence interval, neither the magnitude nor the precision of the primary outcome can be assessed.
The absence of a comparator is also consequential. A single-group study can describe outcomes observed among participants receiving the study regimen, but it does not by itself estimate what would have happened to comparable participants under another treatment. Any comparative interpretation would require additional evidence and assumptions not reported in the registry record. The design should therefore not be read as a randomized test of relative effects.
The registry lists secondary response outcomes and adverse-event information, but it does not report numerical response results or a complete analysis of safety. The serious-event entries can be read as descriptive counts and percentages for the recorded group, not as comparative causal estimates. The registry's terminated status is reported, but the reason is not; it should not be used to infer a favorable or unfavorable outcome.
Overall, the record permits a description of study structure, intended treatment, endpoint definition, and selected safety counts. It does not supply enough outcome or analysis detail to judge the estimated time to progression, its uncertainty, comparative benefit, or the influence of missing data. Those limits are central to interpreting what the record can and cannot establish.
13. Why This Trial Matters Statistically
This trial illustrates why a clear endpoint definition is necessary but not sufficient for statistical interpretation. The registry identifies the time origin, the progression criterion, the unit, and the summary type for time to progression. Those elements help readers understand what the outcome was intended to measure. Yet without the median, full range, event count, or uncertainty interval, the central numerical finding and its precision remain unavailable.
It also highlights the distinction between a treatment study and a comparative treatment study. A single-group design can record outcomes and adverse events in participants receiving an intended regimen. It does not provide a concurrent randomized control group against which differences can be estimated. This distinction is important when readers encounter response or safety figures: observed events are not, by themselves, evidence of a causal effect or a relative risk.
The record further separates planned treatment from received treatment. A regimen schedule can be described precisely, but the schedule does not demonstrate adherence, completion, or exposure for each participant. Statistical interpretation depends on knowing which participants contributed to an outcome and how incomplete follow-up was handled. Those analysis details are not reported in the registry record.
Finally, the entry shows that registry status and statistical results answer different questions. The record identifies the study as terminated, but gives no reason. That label cannot replace outcome data or explain the analysis. Likewise, a planning illustration based on an observed effect is not the same as a prospective design justification or evidence of observed power. Careful reading keeps these distinctions separate and avoids treating missing information as a result.
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 primary limitation for interpretation is that the registry record does not report the numeric time-to-progression result, despite specifying a median and full range. It also does not report a confidence interval, number of progression events, censoring details, or the method used to estimate the endpoint. The timeframe is listed as 34.3 months, but its precise interpretation is not explained in the record.
The study had a single-group design and no stated comparator. Consequently, the record does not offer a randomized basis for estimating comparative effects. The enrollment was 16, and a sample-size justification is not reported in the registry record. No conclusions about the reason for the study's terminated status can be drawn because that reason is not reported.
Several details needed to assess implementation and analysis are absent. The record does not report eligibility criteria, participant characteristics, treatment received, adherence, dose modifications, discontinuation reasons, outcome measurement schedules, or missing-data handling. It identifies all enrolled patients as the primary population, but does not report how incomplete observations or censoring were treated.
The record lists response outcomes but not their numerical results, and lists selected serious adverse-event terms without complete event-level detail. The naming of lenalidomide differs between the registry title and the official title and intervention description; the record does not explain that difference. These gaps limit assessment of treatment exposure, outcome precision, safety completeness, and consistency of the registry entry. None should be filled by assumptions about the protocol or analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: CC-5013 (Lenalidomide) and Rituximab in Waldenstrom's Macroglobulinemia — NCT00142168.
- Registry record last updated 2016-04-21; status last verified 2016-03.
- Results first posted 2015-12-16.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a Phase II, single-group study sponsored by Dana-Farber Cancer Institute, with 16 participants enrolled for Waldenstrom's macroglobulinemia. The intended treatment combined lenalidomide and rituximab. The study is listed as terminated; the reason is not reported in the registry record.
The primary endpoint was time to progression from starting therapy, with progression defined as a 25% increase in serum IgM from nadir. The outcome is described as a median with a full range and has a listed timeframe of 34.3 months, but the numeric median and range are not reported in the registry record. Major and minor response rates are listed as secondary outcomes without numeric results. Serious adverse-event counts and selected event percentages are recorded, but no comparative safety analysis is available.
The record does not report a primary statistical analysis, uncertainty interval, sample-size justification, missing-data method, or reason for termination. Its information supports describing the design and intended endpoint, but not estimating the primary result or a comparative treatment effect.