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 Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma (NCT00294632), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00294632 |
| Phase | Phase 1, Phase 2 |
| Condition | Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 54 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
The study addressed dose finding and treatment activity in people with relapsed lymphoma. Its primary question was what maximum tolerated dose of lenalidomide could be given in combination with rituximab, using dose-limiting toxicity during the first cycle to define the limit. The study also aimed to assess safety and effectiveness across mantle cell lymphoma and diffuse large B-cell non-Hodgkin's lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma.
The record describes a Phase I group receiving lenalidomide with rituximab and a Phase II group labelled lenalidomide. It also lists response outcomes for participants treated at lenalidomide 20 mg. However, it does not report response results or the primary maximum tolerated dose result. The treatment question therefore cannot be answered from the posted outcome information alone.
Population
People with relapsed mantle cell lymphoma or the other lymphoma types named in the study summary. The registry condition is listed as lymphoma; further eligibility details are not reported in the registry record.
Intervention
Lenalidomide with rituximab in the Phase I group. The starting regimen is lenalidomide 10 mg orally daily on Days 1-21 and rituximab 375 mg/m^2 intravenously weekly for 4 weeks. The Phase II group is labelled lenalidomide.
Comparator
There was no randomized comparator. Allocation is listed as NA and the model as single group. The Phase I and Phase II groups are not a like-for-like control comparison.
Primary question
What is the highest lenalidomide dose level, in combination with rituximab, at which no more than 1 participant among 6 experiences dose-limiting toxicity in the first 28 days?
3. Trial Design
The registry classifies the study as Phase I and Phase II, with a single-group model, no masking, and allocation listed as NA. It is marked completed. The study dates in the record are 2006-02 for the start and 2016-02 for primary completion. The recorded enrollment is 54.
The stated aim combines a dose-finding question with safety and effectiveness evaluation. The Phase I group is named Lenalidomide + Rituximab. The regimen description gives a lenalidomide starting dose of 10 mg orally each day on Days 1-21, together with rituximab 375 mg/m^2 intravenously weekly for 4 weeks. The Phase II group is named Lenalidomide. The record also lists response outcomes for participants treated at lenalidomide 20 mg.
These groups do not form a randomized treatment comparison. Their phase labels and treatment descriptions differ, and there is no assigned control arm in the registry design. Any contrast between their reported safety counts would therefore be descriptive rather than a controlled estimate of treatment effect. Differences could reflect which participants entered each phase, treatment exposure, follow-up, or other factors; those details are not reported in the registry record.
The record names lymphoma as the condition and describes relapsed mantle cell lymphoma and several other lymphoma categories in the study summary. It does not provide enough information to establish how participants were distributed across these diagnoses, dose levels, or phases. Nor does it state the criteria used to assign treatment or determine entry into each phase. Such details should not be inferred from the listed arm names.
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: There were 112 participants recruited for registration, 58 were screen failures prior to study inclusion
Phase I Dose Escalation Period
| Stage | Phase I: Lenalidomide + Rituximab | Phase II: Lenalidomide 20 mg + Rituximab |
|---|---|---|
| STARTED | 14 | 0 |
| Cohort 1: 10 mg | 3 | 0 |
| Cohort 2: 15 mg | 3 | 0 |
| Cohort 3: 20 mg | 6 | 0 |
| Cohort 4: 25 mg | 2 | 0 |
| COMPLETED | 14 | 0 |
| NOT COMPLETED | 0 | 0 |
Phase II: 20 mg Lenalidomide
| Stage | Phase I: Lenalidomide + Rituximab | Phase II: Lenalidomide 20 mg + Rituximab |
|---|---|---|
| STARTED | 6 | 38 |
| COMPLETED | 6 | 38 |
| NOT COMPLETED | 0 | 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 | Phase 1: Lenalidomide + Rituximab | Phase II: Lenalidomide 20 mg + Rituximab | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 38 | 52 | |
| Age, Continuous | years | 72 (56 to 84) | 64 (46 to 85) | 66 (46 to 85) |
| Sex: Female, Male: Female | Participants | 2 | 3 | 5 |
| Sex: Female, Male: Male | Participants | 12 | 35 | 47 |
| Region of Enrollment: United States | participants | 14 | 38 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab, measured over 28 days of cycle 1.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of lenalidomide in combination with rituximab, measured in mg. The registry defines this as the highest dose level at which no more than 1 participant among 6 treated experiences a dose-limiting toxicity. A dose-limiting toxicity is defined as any grade III or IV toxicity during the first 28 days, corresponding to the first cycle.
This endpoint is used in dose-finding because it links dose selection to serious toxicity observed during a specified early treatment period. It is not itself a measure of tumor response, long-term safety, or comparative effectiveness. The definition depends on how toxicities are graded, which participants are counted at each dose, and the observed dose-level results. The toxicity grading system and dose-level results are not reported in the registry record.
The registry gives the endpoint definition and timeframe but does not report the selected maximum tolerated dose or the underlying dose-limiting-toxicity counts. The primary endpoint result is therefore unavailable in the posted record. The starting regimen description should not be mistaken for the final maximum tolerated dose: it identifies a starting dose, not an endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry record defines the primary endpoint but does not report its result. It states how maximum tolerated dose was to be identified, and describes dose-limiting toxicity during the first 28 days, but gives no selected dose level or toxicity counts by dose. The record therefore does not establish which dose met the endpoint definition.
The posted safety information gives group-level counts. In the Phase I lenalidomide plus rituximab group, 9 of 14 were recorded as affected by a serious adverse event, and 14 of 14 were recorded for other adverse events. One death is listed. In the Phase II lenalidomide group, 24 of 44 were recorded as affected by a serious adverse event, and 44 of 44 for other adverse events; no deaths are listed. These figures describe what the registry reports for those groups. They do not identify whether events were related to treatment, how many events each participant experienced, or when events occurred.
The record lists neutropenia at 35.7% among the top serious adverse event terms. Lymphopenia and thrombocytopenia are each listed at 9.1%; non-neutropenic infections, hyperuricemia, and hypercalcaemia are each listed at 7.1%. The record does not make clear in the listed terms which group each percentage refers to, so those figures should not be attributed to a particular phase or used to compare groups.
The study is not a randomized comparison. The Phase I and Phase II group labels, differing treatment descriptions, and lack of an assigned control mean that their counts cannot establish that one regimen caused more or fewer events than another. The groups may differ in ways not described in the registry record. Even where a count is large or a percentage appears precise, it remains a descriptive safety report rather than an estimate from a controlled comparison.
Response outcomes are listed, including overall response among participants treated with lenalidomide 20 mg, but no response values are reported in the record. There are no posted analyses listed. Consequently, the available information supports an account of the stated design, endpoint definition, and reported safety counts, but not conclusions about tumor response or the primary dose-finding result.
9. Statistical Methods Explained
What does the dose-finding endpoint mean?
The endpoint uses a threshold rule: among 6 participants treated at a dose level, no more than 1 may experience a dose-limiting toxicity for that level to qualify under the definition. The maximum tolerated dose is the highest dose level that meets that rule. The toxicity window is the first 28 days of treatment, and the registry defines a dose-limiting toxicity as any grade III or IV toxicity in that period.
This rule turns observed early toxicities into a dose-selection criterion. It is not a guarantee that the selected dose will be free of toxicity, nor does it summarize all later adverse events. A dose-finding result also depends on the sequence of dose levels and the number of participants assessed at each level. Those details, along with the observed dose-level results, are not reported in the registry record. The stated starting regimen is not enough to reconstruct the dose-finding analysis.
Why is this not a treatment-effect comparison?
A randomized comparison assigns participants to treatment groups so that a between-group contrast can be interpreted under the study's randomization scheme. This record lists allocation as NA and the design as single group. It therefore does not supply a randomized control comparison. The Phase I combination group and Phase II lenalidomide group have different phase labels and treatment descriptions, so their outcomes should not be treated as though they came from interchangeable arms.
As a general statistical principle, comparisons between non-randomized groups can reflect differences in participant characteristics, treatment exposure, or follow-up as well as treatment. The registry record does not give enough information to assess such differences. Descriptive counts can still report what was recorded in each group, but they cannot by themselves isolate a causal treatment effect.
How should event counts and percentages be read?
A count identifies how many participants were recorded in a category, while a percentage expresses a proportion using some denominator. Interpretation requires knowing the event definition, the population counted, the observation period, and whether each participant is counted once or whether repeated events contribute. The registry lists serious and other adverse-event counts by group and lists selected serious adverse event terms as percentages. It does not provide all the details needed to reconstruct the calculation or determine how repeated events were handled.
General statistical caution applies when interpreting percentages from groups of different sizes: the apparent precision of a percentage does not remove uncertainty about the underlying event frequency. A percentage is also not a measure of severity or causality. The listed safety summaries do not establish that a reported event was caused by treatment.
What would a confidence interval add?
In general, a confidence interval describes the uncertainty around an estimate under a specified statistical method. A narrow interval indicates greater precision under that method, while a wide interval indicates less precision. Intervals can help distinguish a stable estimate from one that is highly uncertain, but they do not correct a biased design or make non-randomized groups comparable.
The registry record lists no analyses and does not report confidence intervals for the outcomes described. Thus, the posted counts and percentages should not be read as though uncertainty has been quantified. In particular, no interval for the primary maximum tolerated dose or response outcome is available in the record.
What does over-dispersion mean in general?
For count outcomes, a simple statistical model may assume that variation follows a particular distribution. Over-dispersion means the observed variation is greater than that model assumes. If ignored, standard errors may be too small and confidence intervals or tests may overstate precision. Whether over-dispersion is relevant depends on the outcome and analysis model. The registry record does not report a model for count outcomes, so it is not possible to say whether this issue was assessed in the study analysis.
How should planning illustrations be interpreted?
The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it varies the effect to detect as a fraction of the observed effect. For time-to-event outcomes, it describes total events; for other outcomes, it describes participants per arm. These are planning assumptions, not evidence that the trial used that design or achieved a particular probability of detecting an effect.
More generally, sample-size planning illustrations are conditional on their assumptions and the chosen effect size. They are not observed power and do not establish whether a trial's actual result is reliable. The registry record does not report the trial's own statistical plan or sample-size justification, so the planning assumptions should not be attributed to the original study design.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 3 outcome measures and identifies a primary maximum tolerated dose endpoint, as well as secondary response outcomes for participants treated at lenalidomide 20 mg. It does not report outcome analyses. The number of analyses listed is 0. No multiplicity procedure, hierarchy among secondary outcomes, or prespecified approach to interpreting multiple tests is reported in the registry record.
Multiplicity is a general concern when several outcomes or comparisons are tested. Repeated testing can increase the chance of finding an apparently notable result by chance, so an analysis plan may specify which outcomes are primary, how secondary outcomes are interpreted, and whether any adjustment is used. No such statistical plan is reported, so it is not possible to determine how the study handled this issue. This does not establish that no plan existed; it means the plan is not reported in the registry record.
Missing-data methods and analysis populations are also not reported in the registry record. The record does not describe how participants who stopped treatment, missed assessments, or lacked outcome measurements were handled. It does not state whether analyses used all enrolled participants, only those who received treatment, or a different population. Without these details, the reported group counts cannot be assumed to represent a particular analysis population or follow-up rule.
These omissions matter for interpreting both safety and response. The denominator and observation period determine what an event frequency means, while the handling of missing outcome measurements can affect response estimates. The posted information does not permit reconstruction of those decisions.
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 |
|---|---|---|---|
| Phase I: Lenalidomide + Rituximab | 9 | 14 | 64.3% |
| Phase II: Lenalidomide | 24 | 44 | 54.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase I: Lenalidomide + Rituximab | 1 of 14 |
| Phase II: Lenalidomide | 0 of 44 |
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 |
|---|---|
| Phase I: Lenalidomide + Rituximab | 14 of 14 |
| Phase II: Lenalidomide | 44 of 44 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I: Lenalidomide + Rituximab | Phase II: Lenalidomide |
|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 5 of 14 | 13 of 44 |
| Thrombocytopenia | Vascular disorders | 1 of 14 | 4 of 44 |
| Lymphopenia | Blood and lymphatic system disorders | 0 of 14 | 4 of 44 |
| Leucopenia/leukocytopenia | Investigations | 1 of 14 | 3 of 44 |
| Hypercalcaemia | Metabolism and nutrition disorders | 1 of 14 | 2 of 44 |
| Hyperuricemia | Metabolism and nutrition disorders | 1 of 14 | 1 of 44 |
| Deep Vein Thrombosis | Vascular disorders | 0 of 14 | 2 of 44 |
| Muscle weakness | Musculoskeletal and connective tissue disorders | 0 of 14 | 2 of 44 |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | 0 of 14 | 2 of 44 |
| Chest Pain | Cardiac disorders | 0 of 14 | 2 of 44 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I: Lenalidomide + Rituximab | Phase II: Lenalidomide |
|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 14 of 14 | 44 of 44 |
| Lymphopenia | Blood and lymphatic system disorders | 14 of 14 | 44 of 44 |
| Leucopenia | Blood and lymphatic system disorders | 13 of 14 | 44 of 44 |
| Thrombocytopenia | Blood and lymphatic system disorders | 14 of 14 | 42 of 44 |
| Hyperglycaemia | Metabolism and nutrition disorders | 14 of 14 | 41 of 44 |
| Anaemia | Blood and lymphatic system disorders | 14 of 14 | 38 of 44 |
| Fatigue | General disorders | 14 of 14 | 38 of 44 |
| Non-neutropenic infections | General disorders | 14 of 14 | 28 of 44 |
| Myalgia | Musculoskeletal and connective tissue disorders | 6 of 14 | 30 of 44 |
| Pruritus | Skin and subcutaneous tissue disorders | 13 of 14 | 22 of 44 |
Serious events with the highest arm-level rate: neutropenia (35.7%), lymphopenia (9.1%), thrombocytopenia (9.1%), non-neutropenic infections (7.1%), hyperuricemia (7.1%).
The safety record reports serious adverse events and other adverse events separately for two named groups. For Phase I: Lenalidomide + Rituximab, the record lists 9 affected among 14 at risk for serious adverse events, 14 affected among 14 at risk for other adverse events, and 1 death. For Phase II: Lenalidomide, it lists 24 affected among 44 at risk for serious adverse events, 44 affected among 44 at risk for other adverse events, and 0 deaths.
These are registry counts, not a randomized comparison. The groups are not like-for-like controls, and the figures do not show whether any event was judged related to treatment. A participant-level count also does not tell how many separate events occurred, how severe each event was, or when it occurred. The observation windows and event-collection details are not reported in the registry record.
The listed serious adverse event terms include neutropenia at 35.7%, lymphopenia and thrombocytopenia at 9.1% each, and non-neutropenic infections, hyperuricemia, and hypercalcaemia at 7.1% each. The record does not identify the group attribution for these percentages in the listed terms. They should therefore be read as reported event-term figures, not as a basis for comparing phases or inferring causation.
12. What the Result Does, and Does Not, Mean
The record documents a completed Phase I and Phase II study with a dose-finding aim, a defined early toxicity rule, and posted group-level safety counts. It also records response outcomes as planned measures. Those details help identify the questions the study was intended to address and describe some of the safety information entered in the registry.
However, the primary maximum tolerated dose result is not reported in the registry record. Neither are response results, despite the listing of outcomes for participants treated at lenalidomide 20 mg. The posted information therefore does not establish the dose selected by the study or the degree of tumor response. It also does not support a conclusion that the combination or lenalidomide alone is effective or ineffective.
The safety counts describe recorded events in the Phase I and Phase II groups. They do not establish treatment causation, and the groups are not randomized comparators. Because details about event timing, follow-up, and analysis populations are absent, the counts should be interpreted as descriptive rather than as a complete comparative safety estimate.
In general, a study can be informative even when a registry record lacks results: it can document the planned endpoint and design. But a stated objective is not an observed finding. A dose-finding definition does not reveal which dose met the rule, and a listed response endpoint does not reveal the response rate. The distinction between protocol description and posted results is especially important for this record.
Accordingly, the strongest defensible reading is limited: the registry records a single-group Phase I and Phase II study, specifies a dose-limiting-toxicity definition for the primary endpoint, and reports safety counts for named groups. The central dose-finding and response results remain unavailable in the registry record.
13. Why This Trial Matters Statistically
This study illustrates a common statistical distinction between a clinical question and the evidence needed to answer it. The registry defines a maximum tolerated dose using early toxicities among participants treated at each dose level. That definition is meaningful as a dose-finding rule, but the rule alone is not the result. Without the selected dose and observed dose-level toxicity counts, readers cannot verify how the endpoint was met.
It also illustrates why design labels matter. A Phase I combination group and a Phase II group labelled lenalidomide do not constitute a randomized comparison. Their safety counts can be described, but treating the groups as controls for one another would require assumptions that the registry record does not support. This distinction prevents descriptive information from being overstated as a causal treatment contrast.
The record further shows why event summaries require context. Counts and percentages are informative only when their denominators, time windows, definitions, and group attribution are clear. The posted safety figures give some counts and selected event-term percentages, but not all of the context needed to make a comparative interpretation.
Finally, the registry lists response outcomes but does not report their results. This makes the difference between planned measurement and reported evidence explicit. For clinical and statistical readers, recognizing that gap is essential: endpoint definitions, study aims, and safety summaries cannot substitute for missing outcome estimates or an analysis plan.
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 main limitation is incomplete outcome reporting in the registry record. Although the primary endpoint is defined, the maximum tolerated dose result and dose-level toxicity counts are not reported. Response results are also absent. The posted information cannot therefore answer the study's dose-finding or response questions.
The registry identifies the design as single group, with allocation listed as NA and no masking. It does not provide a randomized control group. The Phase I combination group and Phase II lenalidomide group should not be treated as directly comparable controls, particularly because the record does not explain participant assignment, phase-specific eligibility, or differences in treatment exposure.
The record does not report important details needed to interpret outcomes: participant characteristics by group, lymphoma subtype distribution, follow-up duration, missing-data handling, analysis populations, toxicity grading procedures, or the statistical analysis plan. It also does not specify the group attribution for the listed serious adverse event percentages. These gaps limit interpretation of both event frequencies and any potential response findings.
The recorded enrollment is 54, while the adverse-event summaries list different group denominators. No explanation for the relationship between the enrollment figure and safety denominators is reported in the registry record. These values should not be combined or reconciled by inference.
Finally, the record gives a starting regimen but not the dose-finding sequence or final dose decision. The starting dose cannot stand in for the primary endpoint result. The posted information is therefore most useful for describing the design and recorded safety summaries, not for estimating comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma — NCT00294632.
- Registry record last updated 2020-02-24; status last verified 2020-02.
- Results first posted 2020-02-24.
- 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
NCT00294632 is a completed Phase I and Phase II, single-group study of lenalidomide and rituximab in relapsed lymphoma. The registry lists enrollment as 54, no masking, and allocation as NA. The Phase I regimen description gives lenalidomide starting at 10 mg orally daily on Days 1-21 with rituximab 375 mg/m^2 intravenously weekly for 4 weeks; the Phase II group is labelled lenalidomide.
The primary endpoint is maximum tolerated dose, defined by dose-limiting toxicity during the first 28 days. The endpoint result is not reported in the registry record. Safety counts are listed for the Phase I and Phase II groups, but the groups are not randomized comparators. Response outcomes are named, but response results are not reported. The record does not provide the analysis plan, missing-data methods, or analysis populations.