Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction (NCT00790842), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy.

2. Clinical Question

The study concerns a population with previously treated multiple myeloma and impaired kidney function. Its stated rationale is that lenalidomide and dexamethasone may have different effects in patients with changes in kidney function. The registry describes a sequence in which Phase I would study side effects and determine a lenalidomide dose, followed by Phase II after a maximum safe and tolerated dose was found.

The primary endpoint is specifically a Phase I safety and dose-finding measure, rather than a direct measure of tumor response or survival. The registry lists overall survival, duration of response, renal function over time, pharmacokinetics, and progression-free survival among secondary outcomes. It does not report outcome estimates for these measures in the information recorded for this trial.

3. Trial Design

This is a Phase I/II study with non-randomized allocation, no masking, and a parallel-group model. The registry records enrollment of 63 and a status of terminated. The study start is recorded as 2009-01-21, and primary completion as 2017-09-30. The reason for termination is not reported in the registry record.

The stated design has a dose-finding Phase I component and a planned Phase II component. Phase I was intended to study side effects and identify a lenalidomide dose when given with low-dose dexamethasone. The registry describes Phase II as studying how well treatment works after a maximum safe and tolerated dose was found. Whether that transition occurred, or how much Phase II evaluation was completed, is not reported in the registry record.

Group descriptions distinguish participants with creatinine clearance 30 - 60 mL/min, participants with creatinine clearance < 30 mL/min who were not on dialysis, and participants with creatinine clearance < 30 mL/min who were on dialysis. Each group description includes lenalidomide at a dose determined in Phase I, dexamethasone 40 mg orally on days 1, 8, 15 and 22 of a 28-day cycle, and anticoagulants. The adverse-event record further separates groups by lenalidomide dose and expansion cohort.

Because allocation was not randomized, group differences may reflect kidney function, dialysis status, dose, cohort, or other differences rather than treatment effects. The registry record does not describe a concurrent control group suitable for a randomized treatment comparison. It also does not report a detailed statistical analysis plan, the criteria used to select the Phase II dose, or the number of participants enrolled in each phase.

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.

Only the first 6 of 11 groups are shown.

Dose Level 1

Reasons for not completing this period:

Dose Level 2

Reasons for not completing this period:

Dose Level 3

Reasons for not completing this period:

Dose Level 4

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients treated during the dose finding phase of the 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.

Population: Eligible, treated patients

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy, measured over First cycle of therapy (28 days).

The primary endpoint counts participants in the Phase I component who experienced a dose-limiting toxicity during the first cycle of therapy, defined as 28 days. The registry definition requires the investigator to judge the event as possibly, probably, or definitely related to lenalidomide. The event qualifies whether or not it resolves.

The specified events include grade 3 or higher neutropenia with fever of at least 38.5 degrees C; grade 4 neutropenia lasting at least 7 days; grade 4 or higher thrombocytopenia; and another grade 4 or higher non-hematologic adverse event that was not present before treatment or was not due to an underlying cause.

This endpoint is used in dose finding because the occurrence of serious treatment-related toxicities can inform whether a dose is tolerable. It is a participant count, not a measure of the severity or duration of every adverse event, and it does not by itself measure antimyeloma activity. The registry record gives the endpoint definition and timeframe but does not report the number of Phase I participants who had a dose-limiting toxicity. Therefore, the observed primary endpoint result cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The most direct statistical description of the primary endpoint is a count of participants who met the dose-limiting toxicity definition during the first cycle. The endpoint is binary at the participant level: a participant either meets the definition during the specified timeframe or does not. The registry labels the outcome as a count of participants, not as a rate per person-time or a time-to-event measure. However, neither the count nor the analyzed Phase I denominator is reported in the registry record.

Why the endpoint is a count

General: for a binary outcome, the observed count can be interpreted alongside the number of participants assessed. Together, those quantities describe how common the outcome was in the analyzed group. A count alone does not describe frequency unless its denominator is clear. Here, the registry supplies the endpoint definition and timeframe but not the observed count or denominator, so a frequency cannot be reconstructed. No recalculated estimate is reported.

The toxicity definition combines several kinds of events, including blood-count abnormalities and other serious non-hematologic events, and requires investigator attribution to lenalidomide at a specified level of suspicion. Combining event types into one endpoint can support dose-finding decisions, but the composite count does not show which qualifying event occurred in each participant. The record does not report a breakdown of primary endpoint events by event type.

What the group structure permits

The trial is described as non-randomized, without masking, and with a parallel-group model. The listed groups reflect kidney function and dialysis status, while the adverse-event entries also distinguish lenalidomide doses and expansion cohorts. These groupings are not randomized treatment arms. General: randomization helps balance measured and unmeasured prognostic characteristics across treatment groups on average. Without it, differences between groups can be due to the characteristics that led to a participant’s group or dose, as well as to treatment itself. The registry record does not report an adjustment strategy that addresses such differences.

For that reason, group-level event counts can describe what was recorded within each group, but they do not establish a causal dose comparison. Small group counts can also be sensitive to individual outcomes. The registry record does not report formal hypothesis tests, adjusted comparisons, or uncertainty intervals for the adverse-event groups.

What can be said about planning

The registry includes a general sample-size planning approach based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning illustrations for specified fractions of an observed effect. These are planning assumptions, not evidence that the study was randomized or that its groups were comparable. The stated approach also says that time-to-event planning uses a total number of events, while other planning quantities are participants per arm.

No numerical planning estimates or observed effect value are reported in the record described. The planning approach therefore cannot be used to infer the trial’s actual sample-size justification, its achieved power, or a treatment effect. General: planning illustrations depend on assumptions about the effect to detect and the analysis model. They are not observed power, and they do not indicate how precisely a completed study estimated its outcome.

Uncertainty and distributional assumptions

General: uncertainty intervals around a binary outcome depend on the observed count, denominator, and chosen method. When counts are sparse, methods designed for small samples may behave differently from large-sample approximations. No interval method or interval estimate for the primary endpoint is reported in the registry record. Over-dispersion is a concern in some count models when variability exceeds what the model assumes; the primary endpoint is specified as a participant count, and the registry does not report a model-based analysis or any assessment of over-dispersion.

The study also lists time-to-event outcomes, including overall survival and progression-free survival. General: time-to-event analysis accounts for how long participants are observed and can accommodate incomplete follow-up through censoring, subject to assumptions about the censoring process. The registry record does not report event counts, follow-up summaries, censoring details, or fitted time-to-event estimates for these outcomes. No conclusions about their statistical precision can be drawn from the listed outcome names alone.

Analysis details not reported

The registry record does not report the statistical analysis plan, missing-data methods, analysis populations, interim analyses, multiplicity procedures, or a sample-size justification for the primary endpoint. It also does not report whether endpoint assessments were independently reviewed or how investigator attribution was handled. These omissions limit interpretation of both the intended analyses and the results that might have been collected. The available statistical description supports an account of the endpoint and design, but not a reconstruction of the primary analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group A Lenalidomide 10 mg/Day", "Group A Lenalidomide 15 mg/Day", "Group A Lenalidomide 25 mg/Day", "Group B Lenalidomide 15 mg/2 Days", "Group B Lenalidomide 25 mg/2 Days", "Group B Lenalidomide 15 mg/Day")
n      <- c(6, 3, 6, 3, 3, 3)
events <- c(0, 0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group A Lenalidomide 10 mg/Day  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Group A Lenalidomide 15 mg/Day  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Group A Lenalidomide 25 mg/Day  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Group B Lenalidomide 15 mg/2 Days  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Group B Lenalidomide 25 mg/2 Days  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Group B Lenalidomide 15 mg/Day  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and three analyses, but does not report the corresponding analysis details or the relationship between those analyses and the outcome measures. It does not describe whether any outcomes were designated for formal hypothesis testing, how multiple comparisons were handled, or whether an outcome hierarchy was prespecified. Multiplicity procedures are therefore not reported in the registry record.

General: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis accounts for the number and structure of tests. This does not mean that every multi-outcome study must use the same correction; the appropriate approach depends on the objectives and planned interpretation. Without a stated plan, the status of any formal comparisons cannot be evaluated.

The primary endpoint is defined for Phase I, but its count and denominator are not reported. The record does not specify the population included in each analysis, whether all enrolled participants were assessed, or how participants without a complete first cycle were handled. Missing-data methods and reasons for missing endpoint observations are not reported in the registry record. The record also does not say how participants who discontinued treatment or had incomplete follow-up contributed to the secondary outcome analyses.

These gaps matter because an analysis population and missing-data approach can affect which participants contribute to an estimate and how that estimate should be interpreted. The enrollment figure of 63 does not establish the denominator for each endpoint. No assumptions about complete follow-up, imputation, or exclusions should be inferred from the registry information.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: lung infection (66.7%), platelet count decreased (50.0%), white blood cell count decreased (50.0%), lymphocyte count decreased (40.0%), anemia (33.3%).

The safety record separates groups by lenalidomide dose and expansion cohort. For each group it lists participants at risk, those affected by serious events, those affected by other events, and deaths. For example, the Group A Lenalidomide 10 mg/Day entry lists 6 at risk, 5 affected by serious events, 5 affected by other events, and 1 death. These are group-specific registry counts and should be read as such rather than combined into an overall treatment comparison.

The record also lists serious adverse-event terms with percentages: lung infection, 66.7%; platelet count decreased, 50.0%; white blood cell count decreased, 50.0%; lymphocyte count decreased, 40.0%; anemia, 33.3%; and other (pancytopenia), 33.3%. The denominator and method used to calculate these term percentages are not reported in the registry record. The terms and percentages therefore do not establish how many distinct participants experienced each event or whether participants could contribute to more than one term.

Deaths are listed by group, but their causes and relationship to treatment are not reported. The safety counts alone do not establish that treatment caused an event, nor do they support a like-for-like comparison among the non-randomized groups.

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

The record describes a study intended to examine tolerability and dose finding for lenalidomide with low-dose dexamethasone in previously treated multiple myeloma with kidney dysfunction, followed by a planned Phase II assessment. Its primary endpoint is a clearly specified Phase I count of participants with dose-limiting toxicities during the first cycle. The registry record does not report that count or its denominator, so the endpoint result itself cannot be interpreted.

The safety information records serious and other adverse-event counts across dose and cohort groups, as well as deaths and selected serious-event terms. These are descriptive observations. Because the study was non-randomized and the groups differ in kidney function, dialysis status, dose, or cohort, the counts do not establish that one dose or group had safer outcomes than another. The term percentages lack a reported denominator, which further limits comparisons and interpretation.

The study’s Phase II objective was to assess how well treatment works, and secondary outcomes include response duration, survival, renal function, pharmacokinetics, and progression-free survival. Their names in the registry do not constitute results. Estimates and uncertainty for these outcomes are not reported in the registry record. The status is terminated, but the reason is not reported; termination alone does not identify why the study ended or what was learned.

General: a study’s design, outcome definitions, and results answer different questions. A stated objective explains what investigators intended to examine; an outcome definition specifies what would be measured; and a reported estimate is needed to describe what the data showed. In this case, the design and endpoint are described, but the primary endpoint estimate and Phase II efficacy findings are not reported. The record therefore does not support a conclusion about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

This trial raises a statistical design question that is important in clinical research: how to evaluate dose and tolerability when participants have differing degrees of kidney dysfunction and dialysis status. The registry separates groups on those characteristics and describes a Phase I dose-finding component before a planned Phase II component. That structure makes the distinction between a dose-finding safety endpoint and later outcome assessment especially important.

The primary endpoint is defined in operational terms, including a 28-day timeframe, investigator assessment of relation to lenalidomide, and specified toxicity criteria. Clear definitions help readers understand what would count as an endpoint event. But a definition cannot replace an observed count and denominator. Their absence means that the central Phase I safety result cannot be evaluated statistically from the registry record.

The non-randomized design also matters. Grouped safety counts can be useful descriptions of the experience recorded within each dose or cohort, but they do not provide the balance that random allocation is intended to create. Dose groups may differ in ways linked to kidney function, dialysis, or study stage. Interpreting their counts as causal comparisons would go beyond what this design supports.

Finally, the record illustrates why registry status, outcome definitions, and reported results should be considered separately. It records termination and a Phase II objective, but does not report the reason for termination or the Phase II outcome estimates. Transparent reporting of endpoint denominators, analysis populations, missing-data handling, and uncertainty would be necessary for a fuller statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the main endpoint is that the registry record defines dose-limiting toxicity but does not report the observed number of affected participants or the analyzed denominator. Without both, the event frequency and its precision cannot be assessed. The enrollment of 63 does not identify the Phase I analysis population or establish how many participants completed the first cycle.

The study is non-randomized and has no masking. The listed groups vary by kidney function, dialysis status, dose, and cohort, so their adverse-event counts are not controlled comparisons. The record does not describe adjustment for differences among groups. Serious-event term percentages are reported without their denominator or aggregation method. Death counts are listed, but causes and treatment relationships are not reported.

The registry status is terminated, but the reason is not reported in the registry record. Although Phase II is described as a planned part of the study, the record does not establish whether the phase proceeded as intended or report efficacy estimates. It also does not report the statistical analysis plan, analysis populations, missing-data methods, interim analyses, multiplicity procedures, or a rationale for the planned sample size. These omissions prevent a detailed assessment of how analyses were conducted and how completely the outcomes were observed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction — NCT00790842.
• Registry record last updated 2018-10-24; status last verified 2018-09.
• Results first posted 2018-10-24.
• 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.

19. Record Summary

NCT00790842 is a Phase I/II, non-randomized, unmasked, parallel study of lenalidomide with low-dose dexamethasone in previously treated multiple myeloma with kidney dysfunction. The record lists enrollment of 63, status as terminated, study start on 2009-01-21, and primary completion on 2017-09-30.

The Phase I primary endpoint counts participants with dose-limiting toxicities during the first 28-day cycle. The endpoint definition is reported, but its observed count and denominator are not reported in the registry record. Group-specific adverse-event counts, deaths, and selected serious-event terms are listed; they are descriptive and do not constitute randomized comparisons. The reason for termination, detailed analysis methods, and Phase II outcome results are not reported in the registry record.