Melphalan, Lenalidomide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Melphalan, Lenalidomide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis (NCT00679367), a na phase 2 study. The primary outcome is Number of Participants With Hematologic Response.

2. Clinical Question

The study asks about hematologic response and treatment side effects in participants receiving the three-drug regimen. Its primary endpoint is a count of participants with a response, rather than a direct comparison of response between treatment groups. The registry identifies the endpoint population as participants who completed at least 3 cycles of treatment.

The record does not report how many participants in that population had a complete or partial response, nor does it provide an estimate of the response rate or its uncertainty. It also does not report an analysis for this endpoint. Therefore, the clinical question can be described from the protocol record, but the posted results do not establish the observed response count.

The registry lists two secondary outcomes: the number of organs improved or stable, and the number of participants removed from study due to toxicities. It does not provide their results in the registry record for this account. The study has no control group, so its design cannot directly distinguish outcomes under this regimen from what would have occurred under another treatment or no study treatment.

3. Trial Design

The registry describes a phase II, single-group trial of melphalan, lenalidomide, and dexamethasone. The listed study arm is “Melphalan Revlimid and Dexamethasone.” Allocation is not applicable, and masking is listed as none. The registry record reports enrollment of 16 and a completed status. The recorded start is 2008-05 and the primary completion is 2015-05.

The trial title and brief summary concern primary systemic amyloidosis, also described in the official title as AL amyloidosis. The registry's condition field lists Multiple Myeloma. This difference in terminology is present in the record; the available information does not explain it.

The primary outcome is the number of participants with a hematologic response at one year. Its stated analysis population is participants who completed at least 3 cycles of treatment. The response definitions include complete response and several forms of partial response, adapted to the participant's measurable disease features. The endpoint is therefore a count, while the definition of response can depend on which disease measure is applicable.

The two listed secondary outcomes concern organ status and removal from study due to toxicities. The registry lists 3 outcome measures and 0 analyses. This means results for the primary and secondary endpoints are not reported in the registry record available for this account; it does not establish whether analyses were or were not performed outside the record.

Because the trial has one treatment group and no randomized comparator, it is not a like-for-like controlled comparison. The registry record does not report a sample-size justification, a detailed statistical analysis plan, or an interim-analysis plan. Any planning illustration based on a two-arm comparison should be understood as hypothetical rather than as a description of the trial's actual design.

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: Participants who completed at least 3 cycles of treatment

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 Hematologic Response, measured over one year.

The primary endpoint is the number of participants with a hematologic response at one year among participants who completed at least 3 cycles of treatment. Hematologic response is defined as either complete or partial response.

Complete response requires no detectable monoclonal protein in serum or urine by immunofixation electrophoresis, a bone marrow biopsy with less than 5% plasma cells without clonal dominance of kappa or lambda isotype, and a normal serum free light chain assay. Partial response is defined according to the disease measure available for an individual participant. The criteria include a reduction of 50% or more in marrow plasma cells, monoclonal peak height, daily light chain excretion, or elevated serum free light chain assay, as applicable.

Using a count of participants with response gives a direct summary of how many in the defined population met the endpoint criteria. The registry's use of individualized measures reflects that disease burden may be assessed in different ways. In general, such a composite definition can accommodate different measurable features, but interpretation depends on clear application of the relevant criterion to each participant.

The registry record does not report the number meeting the endpoint, the number assessed, or an uncertainty interval. Thus, the endpoint definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by identifying the study design and the quantity being measured. This is a single-group study, and the primary outcome is a count of participants with hematologic response at one year. The registry defines a population of participants who completed at least 3 cycles of treatment. It does not report an analysis for this endpoint or the number of participants in that endpoint population.

What does a count measure?

A count reports how many members of a defined group experienced an outcome. In general, a count is different from a response proportion: a proportion requires both the number with the outcome and a denominator that identifies how many were assessed or included. The registry record does not report the primary response count or the endpoint denominator, so neither a response proportion nor its uncertainty can be described from this information.

The enrollment figure is not automatically the denominator for every endpoint. Participants may have different assessment availability or may not meet a defined analysis-population criterion. Here, the primary endpoint population is described as participants who completed at least 3 cycles, but the number meeting that description is not reported in the registry record. It would be inappropriate to substitute enrollment for that missing endpoint denominator.

Why does a confidence interval matter?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. It helps readers distinguish the estimated value from the range of values that remain compatible with the data and method. An interval does not correct for bias, missing data, or limitations in study design. No confidence interval for the primary endpoint is reported in the registry record, and the underlying response result is also not reported.

For a single-group outcome, an interval around a response proportion could describe uncertainty about that group's response proportion, if the required numerator, denominator, and analysis were available. It would not create a controlled treatment comparison. A comparison requires a relevant comparator and an analysis that accounts for the study design. This trial is listed as single group, with allocation not applicable.

What does the planning illustration assume?

The registry's planning assumptions describe a two-arm illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also specify detecting a stated fraction of an observed effect. These assumptions are not the design of this single-group trial. The observed effect and any resulting planning counts are not reported in the registry record for this account. A planning illustration is not evidence about the study's observed outcome, and sample-size planning is not observed power.

In general, a sample-size calculation depends on its target effect, error rate, allocation, outcome model, and other assumptions. Changing those assumptions can change the planning result. The record does not report a trial-specific sample-size justification, so the two-arm planning assumptions should not be treated as an account of how this trial was designed or what it was able to detect.

Why does endpoint definition matter?

The response definition permits complete response or partial response. The complete-response criteria use immunofixation, bone marrow findings, and a serum free light chain assay. Partial response uses a reduction of 50% or more in a specified disease measure, depending on the participant's measurable features. In general, an endpoint with multiple qualifying routes requires consistent application of the prespecified criteria. The registry record does not report participant-level measurements or how many participants met each response category.

The primary endpoint is a count, and the registry does not identify a time-to-event analysis. General methods for survival outcomes, such as methods based on event counts, would not be assumed to apply to this endpoint based on the available record.

What can the adverse-event percentages show?

The registry lists percentages for serious adverse-event terms. These figures describe the listed terms in the study group; they do not compare treatment groups. In general, an adverse-event percentage depends on the event definition, the assessment period, and the number of participants at risk or assessed. The record's listed serious-event terms do not include term-specific event counts or timing in the information available for this account. The percentages alone also do not show whether a term was judged related to treatment.

The registry record gives no analysis results for the efficacy endpoints. Statistical explanations can clarify what an estimate, denominator, or interval would mean in general, but they cannot supply the missing observed response result. The posted information supports a description of the design and endpoint definitions, not a quantitative estimate of hematologic response.

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("Melphalan Revlimid and Dexamethasone")
n      <- c(14)
events <- c(7)
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  Melphalan Revlimid and Dexamethasone  14  7  50.0  23.0  77.0  26.8  73.2  26.6  73.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary hematologic-response outcome and two secondary outcomes: organ improvement or stability, and removal from study due to toxicities. It reports 3 outcome measures and 0 analyses. No multiplicity plan is reported in the registry record. In general, when several outcomes are tested, a prespecified approach to multiplicity can help clarify how to interpret statistical evidence across those outcomes. Without a reported plan or analysis results, it is not possible to determine whether or how multiplicity was addressed.

The record does not report how missing outcome assessments were handled, whether participants who did not complete treatment were included in any analysis, or how the endpoint population was determined in practice. The stated primary population is participants who completed at least 3 cycles of treatment. The number meeting that criterion is not reported in the registry record. General methods for missing data depend on why measurements are missing and on the analysis objective; no method can be attributed to this trial from the recorded information.

The registry does not report an analysis population beyond the endpoint description, nor does it provide a participant flow or the number assessed for the primary outcome. The number enrolled is 16, but enrollment alone does not identify the denominator used for the one-year endpoint. It is therefore not possible to assess attrition, compare enrolled and analyzed populations, or judge how missing assessments might affect the result.

These omissions concern what is documented in the registry record. They do not establish that the investigators failed to make an analysis plan or conduct analyses; those details are not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (37.5%), dyspnea (37.5%), fatigue (31.2%), leukopenia (31.2%), heart failure (25.0%).

The registry lists six top serious adverse-event terms for the study group: neutropenia and dyspnea at 37.5% each, fatigue and leukopenia at 31.2% each, and heart failure and infection at 25.0% each. These are descriptive percentages attached to the named terms. They do not establish that an event was caused by treatment, and they do not compare the regimen with another treatment.

The adverse-event record lists 16 participants at risk and 16 affected in both its serious and other adverse-event group fields. The term-specific event counts and timing are not reported in the registry record available for this account. The record also does not report deaths in the adverse-event information. Because one participant may potentially be associated with more than one adverse-event term, term percentages should not be added together or read as mutually exclusive categories.

In general, safety percentages are most interpretable when the event definition, observation period, denominator, severity, and attribution are clear. The registry record's listed terms give a descriptive account, but the available information does not provide those additional details for each term. The figures should therefore be read as reported safety summaries rather than as comparative or causal estimates.

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

This record establishes that a completed phase II, single-group study evaluated melphalan, lenalidomide, and dexamethasone for primary systemic amyloidosis. It specifies a one-year hematologic-response endpoint, defines complete and partial response, and identifies the endpoint population as participants who completed at least 3 cycles. It also records descriptive serious adverse-event terms.

The record does not report how many participants had a hematologic response, how many were assessed at one year, or an estimate of response precision. It does not report results for the listed secondary outcomes or an analysis. Thus, the endpoint definition and study enrollment do not show the observed response result. No conclusion about the frequency of response can be drawn from the information recorded.

The single-group design also does not provide a randomized comparison. In general, outcomes observed in one treatment group cannot by themselves identify what would have happened to similar participants under a different treatment. The record therefore does not establish a comparative treatment effect. It also does not provide a basis to conclude that the regimen does or does not work.

The serious adverse-event percentages describe terms recorded for the study group, but the available information does not provide term-specific event counts, timing, or a comparator. These figures should not be interpreted as comparative risks or as proof that treatment caused the events.

Overall, the record supports an account of the trial's stated question, design, endpoint criteria, and listed safety terms. The missing outcome analyses and results prevent quantitative interpretation of hematologic response or the secondary outcomes. This distinction is important: a completed study record can document what was planned and reported without providing enough information to estimate the endpoint result.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and endpoint results are separate pieces of evidence. The registry describes a detailed hematologic-response definition, including complete response criteria and several possible partial-response measures. That definition helps clarify what the study intended to count, but without the observed count and denominator it cannot answer how often the endpoint occurred.

It also demonstrates the inferential limits of a single-group design. The record identifies one treatment arm and no randomized comparator. A descriptive outcome can characterize that group, but it cannot on its own provide a controlled estimate of how outcomes differ under another treatment. This distinction matters whenever registry outcomes are interpreted alongside results from other studies.

The stated primary population is restricted to participants who completed at least 3 cycles. Because the record does not report how many participants met that criterion or how missing endpoint assessments were handled, readers cannot assess the relationship between enrollment and the analyzed population. In general, clearly reporting participant flow and analysis denominators is important for understanding who contributes to an endpoint estimate.

The record further separates trial status from statistical reporting. It is marked completed, yet the primary outcome result and analyses are not reported in the registry record available for this account. Completion alone does not provide an estimate or its precision. These features make the study useful for illustrating how design, population definition, endpoint reporting, and analysis availability jointly shape what can be interpreted.

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 interpreting the trial is that the registry record does not report the primary hematologic-response result or an analysis. Although the endpoint is defined and the study is marked completed, no response count, endpoint denominator, or confidence interval is available in the record. The registry lists 0 analyses.

The primary endpoint population is participants who completed at least 3 cycles of treatment, but the number meeting this criterion is not reported. The record also does not report missing-data handling, participant flow, or the number assessed at one year. Enrollment of 16 cannot be substituted for the missing endpoint denominator.

The single-group design has no randomized comparator. It therefore cannot directly estimate a treatment contrast, and the registry's two-arm planning assumptions should not be confused with the study's actual design. A trial-specific sample-size justification, interim-analysis plan, and statistical analysis plan are not reported in the registry record.

The registry lists serious adverse-event terms as percentages but does not report term-specific event counts, timing, attribution, or comparative safety data in the information available for this account. Deaths are not reported in the adverse-event information. These limitations constrain interpretation of both benefit and safety.

Finally, the record's condition field lists Multiple Myeloma, while its title and summary describe primary systemic amyloidosis or AL amyloidosis. The available information does not explain this difference. The record also does not report results for the secondary outcomes concerning organ status and removal from study due to toxicities.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Melphalan, Lenalidomide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis — NCT00679367.
• Registry record last updated 2017-02-20; status last verified 2016-12.
• Results first posted 2017-02-20.
• 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

NCT00679367 is a completed phase II, single-group study sponsored by Boston Medical Center. The record lists enrollment of 16, a start date of 2008-05, and a primary completion date of 2015-05. Masking is listed as none, and allocation is not applicable.

The trial evaluates melphalan, lenalidomide, and dexamethasone. Its primary outcome is the number of participants with hematologic response at one year among those who completed at least 3 cycles. The registry defines complete and partial response but does not report the response result or an analysis. Two secondary outcomes concern organ status and removal from study due to toxicities; their results are not reported in the registry record available for this account.

The record lists serious adverse-event terms and percentages, but does not provide the primary endpoint's observed result or a controlled treatment comparison. The condition field lists Multiple Myeloma, while the trial title and summary describe primary systemic amyloidosis.