Thalidomide to Overcome Lenalidomide Resistance After Autologous Hematopoietic Stem Cell Transplantation (HCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Thalidomide to Overcome Lenalidomide Resistance After Autologous Hematopoietic Stem Cell Transplantation (HCT) (NCT01927718), a na na study. The primary outcome is Number of Participants With Response.

2. Clinical Question

3. Trial Design

This was a pilot study of thalidomide added to lenalidomide maintenance for multiple myeloma after biochemical progression following autologous hematopoietic stem cell transplantation. The record identifies M.D. Anderson Cancer Center as the sponsor and lists 10 participants enrolled. The study is classified as single-group, with allocation recorded as NA and masking recorded as NONE. No randomized comparison is described.

The intervention group is named Thalidomide + Lenalidomide. Thalidomide was listed at 100 mg by mouth daily for 28 days in a 28-day cycle, beginning after clinical documentation of biochemical progression. Lenalidomide was to continue by mouth at the previous dose. The description lists several dose and schedule options, but its final text is incomplete in the registry record, so the full dosing description is not reported there. Questionnaires were also listed among the interventions, consistent with the stated interest in quality of life.

The study start is recorded as 2014-01 and primary completion as 2016-11. Its status is TERMINATED. The reason for termination is not reported in the registry record. The phase is listed as NA. The record does not report a control group, randomization procedure, masking beyond NONE, or a rationale for the enrollment target. These absences limit what can be said about the study's intended design beyond the single-group pilot structure and listed interventions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Response, measured over 3 months.

The primary endpoint is titled Number of Participants With Response, with a timeframe of 3 months after starting the combination. The description defines response rate as the proportion of participants whose disease stabilizes or returns to at least its response level before progression. The listed response categories include stringent complete remission, complete remission, very good partial response, partial response, and stable disease. The detailed definition in the registry record is truncated, so the full operational criteria are not reported there.

A response endpoint can make a clinical question concrete by applying stated disease-status criteria at a specified assessment time. In general, a proportion expresses how many participants in a group meet a defined condition. In this study, the question is whether participants receiving the combination met the registry's response definition at the specified assessment. The measure is not a time-to-event endpoint, and the record does not specify a duration of response measure.

The registry lists one outcome measure but does not report an observed response count or proportion. Therefore, the endpoint's planned definition and timing can be described, but the posted record does not support a numerical estimate of response or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary measure as a binary count of participants with an event, where the event is meeting the response definition. For a binary outcome, each participant is categorized according to whether the specified condition occurred. A count gives the number meeting the condition; a response rate expresses that count in relation to the number assessed. The registry record identifies the endpoint but does not report the observed count, rate, or number assessed.

What does a confidence interval describe?

In general, a confidence interval describes the uncertainty around an estimate under a statistical procedure and its assumptions. For a response proportion, it would indicate a range of values compatible with the observed data and method. It does not guarantee that the true value lies in that particular interval, and it does not resolve limitations in the design or the data. The registry record does not report a response estimate or interval for this endpoint, nor does it identify an interval-estimation method.

What can a single-group design estimate?

A single-group study can describe outcomes among the participants receiving the intervention. Without a separate comparator, it cannot directly estimate a treatment contrast. A contrast requires outcomes under more than one study condition or an explicitly described alternative analysis. The record classifies this study as single-group and does not report a comparator arm. Therefore, the main endpoint, if reported, would be a description of response in the treated group rather than a randomized estimate of the added effect of thalidomide.

The record lists allocation as NA and masking as NONE. It does not report a randomization scheme, a blinded outcome assessment, or an analysis adjusting for other factors. It would be inappropriate to infer such procedures from the pilot label or the endpoint definition. Whether the response assessment was independently reviewed is not reported in the registry record.

How should planning calculations be read?

In general, sample-size planning calculations describe the group sizes that could be needed under specified assumptions about an effect, variability, significance level, allocation, and statistical method. They are planning illustrations, not observed findings and not a measure of the probability that a completed study has detected an effect. The stated planning framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. It also specifies that non-time-to-event illustrations are expressed as participants per arm.

Those planning assumptions do not describe the actual trial design: this registry record lists a single group and no like-for-like control arm. A planning illustration based on an observed effect is not a substitute for a reported endpoint estimate, and it should not be called observed power. The registry does not report the trial's own sample-size justification, nor does it say that the study was designed with the stated planning assumptions. The numerical planning outputs and the effect estimate used for them are not reported in the registry information.

Why does the response definition matter?

Statistical interpretation depends on a reproducible outcome definition. The registry description names response categories and gives some criteria, but the text ends partway through the listing. That truncation leaves the complete endpoint rules unavailable in the registry record. In general, differences in assessment rules, timing, or handling of borderline cases can affect which participants are classified as responders. The record does not specify how such cases were resolved, whether assessments were centralized, or how missing assessments were treated.

Because only the endpoint title and definition are available, and no analysis count is reported, no test statistic, p-value, adjusted estimate, or model result can be described. The registry lists zero analyses. The precise statistical method intended for the primary endpoint is not reported in the registry record. These distinctions matter: an endpoint description indicates what the investigators aimed to measure, while an analysis result would show what the enrolled participants' data yielded under a specified method.

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("Thalidomide + Lenalidomide")
n      <- c(10)
events <- c(2)
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  Thalidomide + Lenalidomide  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, identified as the primary response count, and zero analyses. It does not report a multiplicity strategy, such as how testing across outcomes or time points would be controlled. The record also does not identify additional primary or secondary statistical hypotheses. The stated interest in quality of life is part of the study summary, and questionnaires are listed as an intervention, but a quality-of-life outcome measure or analysis is not described in the record presented.

Missing-data handling is not reported in the registry record. In particular, the record does not say how participants without a 3-month assessment would be classified, whether an assessment window was allowed, or whether any imputation method was planned. The number enrolled does not establish how many had an evaluable endpoint. Without those details, the denominator for any response proportion cannot be determined from enrollment alone.

The analysis population is not reported. The record does not specify whether the primary analysis would include all enrolled participants, only participants who began the combination, or only those with an observed 3-month assessment. The statistical analysis plan, analysis populations, and rules for protocol deviations are not reported. Consequently, the registry description is insufficient to determine how incomplete follow-up or departures from the intended regimen would have affected the primary analysis.

These omissions do not establish that such methods were absent from study conduct; they mean that they are not reported in the registry record. They constrain interpretation because the response estimate, if reported elsewhere, would need to be understood alongside the denominator, missing-data rules, analysis population, and any multiplicity approach.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event listing identifies the Thalidomide + Lenalidomide group. For serious adverse events, 10 participants are listed as at risk and 0 as affected. For the other adverse-event category, 10 are listed as at risk and 10 as affected. These are counts for the study group, not comparative estimates, because the record describes no separate control group.

The registry does not list serious adverse-event terms. That empty term listing should be read together with the recorded count of 0 affected participants for serious adverse events, rather than as a description of particular event types. For other adverse events, the count indicates that all 10 participants at risk were listed as affected, but the event types and the number or severity of events per participant are not reported in the information available.

Deaths are recorded as null. Null does not report a zero count, so it should not be interpreted as confirmation that no deaths occurred. The record also does not report follow-up duration for safety, event timing, attribution, or detailed event definitions. These counts therefore summarize what the registry lists; they do not establish comparative safety or describe the full clinical context of each event.

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

The registry describes a pilot investigation of adding thalidomide to continued lenalidomide maintenance after biochemical progression in multiple myeloma following autologous transplantation. It specifies a response endpoint at 3 months and lists 10 participants enrolled. Those details establish the study's stated question and scale, but the registry record does not report the observed response count or rate. The central efficacy result therefore cannot be quantified from the available record.

Even if a response result were available, the single-group structure would restrict what it could establish. The result would describe the participants receiving the combination, not a difference against a concurrent control group. Without a comparator, changes in disease status cannot be separated from other influences using a randomized comparison. This limitation is especially important when interpreting a study framed around overcoming resistance: the title and rationale do not themselves demonstrate that the intervention changed outcomes.

The recorded adverse-event counts describe events in the treated group, but they do not provide a comparative safety estimate. The serious adverse-event count is listed as 0 affected among 10 at risk; the other-event count is listed as 10 affected among 10 at risk. The types and clinical detail for other events are not reported in the registry information, and the deaths field is null rather than a reported zero.

The terminated status and the absence of a reported reason add uncertainty about study completion and reporting. The record does not establish whether all intended assessments were completed or why the study ended. It also does not report missing-data rules or the analysis population. Consequently, the most defensible reading is descriptive: the record documents a small single-group study and its planned endpoint, but does not provide the response analysis needed to judge the observed outcome. It supports neither a conclusion of benefit nor a conclusion of no benefit.

14. Why This Trial Matters Statistically

This study raises a statistically important question about how to interpret an intervention evaluated in a small, single-group pilot. The registry identifies a clinical setting, a treatment combination, and a response assessment at 3 months. But an endpoint definition is not an endpoint result: without the observed count and denominator, the response proportion and its precision cannot be assessed from the registry record.

The design also illustrates the distinction between describing an outcome and estimating a treatment effect. A single-group response result could characterize what happened among participants receiving the combination. It would not supply the randomized comparison needed to estimate the difference between combination therapy and a control condition. Statistical language should reflect that distinction, even when the study's title or rationale emphasizes overcoming resistance.

The small enrollment makes transparent reporting particularly important. Counts, denominators, assessment completeness, and uncertainty would all be needed to understand the response outcome. The registry record lists 10 enrolled but does not report how many had an evaluable response assessment. It also does not report an analysis population or missing-data approach. Those omissions prevent readers from reconstructing the endpoint analysis.

The record further distinguishes planning assumptions from study design. A planning illustration based on an observed effect does not establish that the trial had adequate power, and the stated two-arm planning assumptions do not match the registry's single-group classification. This is a useful reminder that planning calculations must be interpreted in the context of the design they assume. In this case, the registry supports a cautious description of what was intended and recorded, not an inference about comparative treatment effects.

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 registry record has limitations specific to interpreting this study. It reports a single-group design with no separate control arm, so it cannot support a direct comparison of the combination against another regimen. Allocation is listed as NA and masking as NONE. No randomization or blinded assessment procedure is reported.

The primary endpoint is defined for assessment at 3 months, but its observed response count and rate are not reported. The endpoint description is truncated, so the full response criteria are not available in the registry record. The number enrolled does not establish the number assessed at the endpoint, and the record does not give the analysis denominator, analysis population, or missing-data method.

The registry status is TERMINATED, but the reason is not reported. The record does not establish whether termination affected recruitment, follow-up, endpoint assessment, or analysis. It also does not report a statistical analysis plan, an endpoint analysis, or a sample-size justification. The stated planning assumptions describe an illustration, not the study's reported design rationale.

The treatment description is also incomplete: the listed lenalidomide schedule ends before the full dosing description is given. Although questionnaires are listed and quality of life appears in the study summary, no quality-of-life outcome result is reported. For safety, the record lists counts but provides limited event detail; deaths are null rather than reported as zero. These gaps constrain interpretation of both the primary outcome and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Thalidomide to Overcome Lenalidomide Resistance After Autologous Hematopoietic Stem Cell Transplantation (HCT) — NCT01927718.
• Registry record last updated 2019-04-29; status last verified 2019-04.
• Results first posted 2019-04-29.
• 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

NCT01927718 is a terminated, single-group pilot study sponsored by M.D. Anderson Cancer Center. It enrolled 10 participants with myeloma and examined thalidomide added to continued lenalidomide maintenance after biochemical progression following autologous hematopoietic stem cell transplantation. The recorded start is 2014-01, and primary completion is 2016-11.

The primary endpoint was the number of participants with response at 3 months, using a definition that included stable disease or return to at least the previous response level. The observed response result is not reported in the registry record. Serious adverse events are listed as affecting 0 of 10 participants at risk; other adverse events are listed as affecting 10 of 10 at risk. Deaths are recorded as null. No comparator group, primary analysis result, reason for termination, or complete statistical analysis plan is reported.