Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma (NCT02086552), a na phase 2 study. The primary outcome is Complete Response, Assessed Using the International Myeloma Working Group (IMWG) Uniform Response Criteria.

2. Clinical Question

The central statistical question is how the response proportion was defined and how much uncertainty surrounds it. The registry record describes an exact binomial 95% confidence interval as the planned way to express uncertainty, but does not report the observed proportion or interval. Without those results, the response frequency and its precision cannot be assessed from this record.

3. Trial Design

This was a phase 2, single-group trial sponsored by Mayo Clinic. It is listed as completed, with a start date of 2014-01-17 and a primary completion date of 2018-01-15. Enrollment was 28. The study was not masked, and allocation is listed as not applicable. No randomized control group is described.

The treatment combined sonidegib with lenalidomide after autologous stem cell transplant. Sonidegib was administered orally once daily on days 1–28 of each course, while lenalidomide was administered orally once daily on days 1–21. Courses repeated every 28 days for up to 18 courses, unless progression or unacceptable toxicity occurred. The treatment description says that patients achieving the listed response or disease-status categories continued treatment.

The registry describes recurrent and refractory plasma cell myeloma as the conditions under study. The primary outcome was complete response or higher, assessed by IMWG uniform response criteria, with a timeframe of up to 2 years. Secondary outcomes listed were overall survival, progression-free survival at 1 year, and progression-free survival. The registry lists 5 outcome measures, but numerical results for these outcomes are not reported in the registry record.

Of the 28 registered patients, one cancelled before treatment and 1 was ineligible because of a protocol violation. The primary analysis population is described as 26 patients. The record does not provide additional detail about the flow of participants through treatment or follow-up. It also does not report a comparator group, a randomization procedure, or masking.

The registry record does not report the rationale for the planned enrollment, a formal sample-size justification, or a detailed statistical analysis plan. The single-group design means the recorded outcomes can describe the treated cohort, but cannot by themselves separate treatment effects from other factors that may influence response or follow-up.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the 28 patients registered, one cancelled prior to treatment and 1 was ineligible due to protocol violation. Therefore 26 patients were used in this analysis.

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: All patients registered to treatment were used to evaluate baseline characteristics.

6. Primary Endpoint

The registry lists the primary outcome as Complete Response, Assessed Using the International Myeloma Working Group (IMWG) Uniform Response Criteria, measured over Up to 2 years.

The primary endpoint measured the proportion of evaluable patients who achieved a complete response or a deeper response, using International Myeloma Working Group uniform response criteria. The registry record defines a confirmed complete response as a complete response recorded at two consecutive evaluations. The criteria listed include negative serum and urine immunofixation, disappearance of any soft tissue plasmacytoma, and fewer than 5% plasma cells in bone marrow. If serum free light chain was the only measurable disease, a normal free light chain ratio was also required.

The denominator was the total number of evaluable patients. The registry record says 26 patients were used in this analysis after one registered patient cancelled before treatment and 1 was deemed ineligible because of a protocol violation. The endpoint timeframe was up to 2 years.

A response proportion is useful because it expresses how frequently the defined outcome occurred in the analysis population. A confidence interval adds information about statistical uncertainty: it gives a range of values compatible with the observed data under the stated method. The record specifies exact binomial 95% confidence intervals for the true success proportion. However, neither the observed response count or proportion nor the interval is reported in the registry record, so the endpoint’s result and precision cannot be interpreted from the available information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary endpoint: each evaluable patient either met the definition of complete response or higher within the specified timeframe, or did not. A proportion summarizes the frequency of that outcome in the analysis population. The registry record states that the denominator was the total number of evaluable patients and identifies 26 patients for this analysis. It does not report the number meeting the endpoint or the resulting proportion.

What does an exact binomial confidence interval describe?

The registry record specifies exact binomial 95% confidence intervals for the true success proportion. In general, a confidence interval describes statistical uncertainty around an estimate. For a binary outcome, the estimate is based on the number of patients meeting the endpoint relative to the analysis population. An exact binomial method uses the binomial model directly rather than relying on a normal approximation to the proportion. The interval’s width depends on the observed outcome count and the number of observations. Because the response count and interval are not reported in the registry record, neither the estimate nor its precision can be assessed.

A confidence interval is not a guarantee that the true value lies within the interval, nor does it address every source of uncertainty. It does not correct for the absence of a control group, differences in patient characteristics, outcome assessment issues, or missing follow-up. It describes uncertainty under the statistical model and analysis assumptions used.

How does the endpoint definition affect interpretation?

Response criteria determine which observations count as successes. Here, the registry describes a confirmed complete response as one noted at two consecutive evaluations, and it lists additional laboratory and disease-assessment conditions. Requiring confirmation can distinguish a persistent recorded response from a response noted at only one evaluation. The use of a formal response definition makes the endpoint more reproducible than an undefined judgment, although the record does not provide further information about assessment procedures or adjudication.

The primary outcome is expressed as a proportion rather than as time until an event. This is different from overall survival or progression-free survival, which are time-to-event outcomes. The record lists those outcomes as secondary measures, but does not report their numerical results or further analysis details. No time-to-event estimate or interpretation can therefore be made from this information.

What can a single-group design estimate?

A single-group trial can describe the observed outcome frequency among its participants. It does not, on its own, estimate a contrast between the treatment and a control condition. Without random allocation to a comparator, changes or outcomes cannot be attributed uniquely to the study treatment. General factors, patient selection, prior treatment, and other aspects of care may also be relevant; the record does not provide information to quantify their influence.

The registry lists allocation as not applicable, masking as none, and the model as single group. These features matter when interpreting the endpoint: the response proportion, if reported, would be a cohort description rather than a randomized treatment-effect estimate. No adjustment or comparative analysis is described in the record.

What is known about the analysis population?

The record says 28 patients were registered, one cancelled before treatment, and 1 was ineligible because of a protocol violation; 26 patients were used in the primary analysis. These exclusions explain the difference between enrollment and the stated analysis population. The record does not explain how missing endpoint assessments were handled, whether every patient in the analysis had complete follow-up, or whether additional analysis populations were used. It also does not report sensitivity analyses addressing missing or uncertain outcome information.

For safety, the registry reports 27 participants at risk in the treatment group, distinct from the 26-patient primary analysis population. These are different reported denominators for different purposes. The record does not explain the discrepancy in population counts or specify the detailed safety observation period. They should therefore be read as the denominators stated for the respective safety summaries, not assumed to be interchangeable.

What does the record say about analysis planning?

The registry record states that exact binomial 95% confidence intervals were to be calculated for the true success proportion. It does not report a formal sample-size justification, the assumptions used to choose enrollment, or a detailed statistical analysis plan. It also lists no analyses in the record. Interim analyses, methods for adjusting for multiple outcomes, and other analytical decisions are not reported in the registry record.

In general, sample-size planning concerns the amount of information needed to estimate an outcome or detect a prespecified effect under stated assumptions. A planning illustration based on an observed effect is not the same as a prospective design justification and is not observed power. The registry record does not document its own sample-size rationale, so the adequacy of planned enrollment for the primary endpoint cannot be evaluated from this information.

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("Treatment (Sonidegib, Lenalidomide)")
n      <- c(26)
events <- c(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  Treatment (Sonidegib, Lenalidomide)  26  0  0.0  0.0  13.2  0.0  12.9  0.1  12.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, including overall survival, progression-free survival at 1 year, and progression-free survival. It also lists 5 outcome measures. When multiple outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately without accounting for multiplicity. Methods such as prespecifying a primary endpoint or adjusting inference can address particular multiplicity concerns, but the record does not report whether any such approach was planned.

The record describes an exact binomial 95% confidence interval for the primary success proportion. It does not report a multiplicity adjustment, a hierarchy for secondary outcomes, or a detailed statistical analysis plan. The number of analyses listed is 0. Interim analyses and stopping rules are not reported in the registry record.

The primary analysis population is described as 26 evaluable patients. The record explains that one of the 28 registered patients cancelled before treatment and 1 was ineligible because of a protocol violation. It does not report how other missing or unassessable outcome data were handled, whether patients with incomplete follow-up were present, or whether an alternative population was analyzed. These details matter because exclusion or missingness can affect which participants contribute to an outcome estimate.

Accordingly, the stated analysis denominator and the reasons for two exclusions are known, but the broader missing-data procedures and multiplicity strategy are not reported in the registry record. The available information is insufficient to judge how those issues were addressed in the analysis.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (3.7%), nausea (3.7%), lung infection (3.7%), syncope (3.7%), acute kidney injury (3.7%).

The safety summary reports 27 participants at risk for serious adverse events, with 5 affected. For other adverse events, it reports 27 at risk and 27 affected. The reported death count is 0. These figures describe the treatment group; without a comparator group, they do not estimate how risks differ from another treatment or from no treatment.

The serious adverse event terms listed are febrile neutropenia, nausea, lung infection, syncope, acute kidney injury, and hematuria. Each is reported at 3.7%. The listing does not establish that these events were mutually exclusive, so the percentages should not be added together. It also does not provide event severity grades, timing, duration, relatedness assessments, or the number of recurrent events for each term.

The safety denominator is 27, while the primary endpoint analysis used 26 patients. The registry record does not explain the difference between these populations. Safety results should therefore be interpreted using the denominator stated for each safety measure. The reported counts and percentages are descriptive summaries, not evidence of comparative safety.

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

The record establishes that a phase 2, single-group trial evaluated sonidegib and lenalidomide maintenance after autologous stem cell transplant in patients with recurrent or refractory plasma cell myeloma. It specifies the treatment schedule, the primary response definition, the analysis population, and selected safety summaries. These details help identify what was studied and how the primary endpoint was intended to be counted.

However, the numerical primary response result is not reported in the registry record. There is no reported response count, proportion, or confidence interval to interpret. As a result, the record does not establish the frequency of complete response or higher in the analysis population or the precision of an estimate.

The single-group design also limits what any response result could establish. Without a randomized comparison, an observed response proportion would describe outcomes in the treated cohort but would not by itself show what would have happened under a different treatment or without the study regimen. No comparative treatment effect can be inferred from this design description.

The safety figures report events in the study group, including serious adverse events and other adverse events. They do not quantify comparative risks, and the registry information does not give detailed event-level context. A zero death count in the reported summary does not resolve questions about other outcomes or comparative safety.

The record lists secondary survival outcomes but does not report their numerical findings. Therefore, it does not support conclusions about survival or progression outcomes. Missing numerical results should not be interpreted as either favorable or unfavorable findings; they indicate that those outcomes cannot be evaluated from the information reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises several statistical issues common to early-phase clinical research. Its primary endpoint is a defined binary response, and the registry specifies an exact binomial confidence interval. Together, these identify both the outcome being counted and the intended way to express uncertainty. In practice, an estimate without its uncertainty can be difficult to interpret, particularly when the analysis population is limited. Here, the numerical response estimate and interval are not reported in the registry record.

The single-group design is also central to interpretation. It can describe the experience of participants receiving the regimen, but it does not create a randomized comparison. The distinction between describing an outcome and estimating a treatment contrast is important: the latter requires a suitable comparison and analysis that addresses differences between groups.

The record also makes the analysis population visible. It reports 28 registered patients, explains that one cancelled before treatment and 1 was ineligible, and identifies 26 patients for the primary analysis. This information helps readers distinguish enrollment from the denominator used for the endpoint. At the same time, unreported details about other missing data and follow-up limit assessment of the analysis.

Finally, the registry lists multiple outcomes, while its record does not describe a multiplicity strategy or detailed analysis plan. These omissions do not establish that a particular analysis was inappropriate; they mean that key features needed to evaluate the statistical interpretation are not available in the record. Clear reporting of estimates, uncertainty, analysis populations, and methods is essential for readers to judge what the observed data can support.

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 main limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. The response count, proportion, and 95% confidence interval are unavailable, so the response frequency and its precision cannot be evaluated. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study used a single group and had no randomized comparator. Even if the response result were available, it would describe outcomes in the treated cohort rather than establish a comparative treatment effect. The record lists no masking, and does not describe procedures for independent response assessment or adjudication.

The stated primary analysis population was 26 patients, following the reported cancellation and ineligibility among 28 registered patients. The record does not describe how other missing outcome data, incomplete follow-up, or sensitivity analyses were handled. Safety summaries use 27 participants at risk, and the reason for the difference from the primary analysis population is not reported in the registry record.

The registry does not report the sample-size rationale, detailed statistical analysis plan, multiplicity approach, interim analyses, or stopping rules. It also does not provide further detail about the observation period or event-level information for the safety summaries. These gaps limit assessment of planned inference and the context of adverse events. They do not establish that a method was or was not used; the relevant information is simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma — NCT02086552.
• Registry record last updated 2021-12-03; status last verified 2021-12.
• Results first posted 2019-05-29.
• 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

This completed phase 2 trial studied sonidegib plus lenalidomide maintenance after autologous stem cell transplant in patients with recurrent or refractory plasma cell myeloma. It was a non-masked, single-group study with enrollment of 28. The primary endpoint was complete response or higher, assessed using IMWG uniform response criteria, with a timeframe of up to 2 years.

The registry identifies 26 patients for the primary analysis after one cancellation and 1 protocol-violation ineligibility. It specifies exact binomial 95% confidence intervals but does not report the numerical primary response result. Secondary outcomes include overall survival and progression-free survival measures; their numerical results are not reported in the registry record.

The safety summary reports 5 serious adverse event-affected participants among 27 at risk, 27 participants with other adverse events among 27 at risk, and 0 deaths. These are descriptive figures without a comparative control group.