Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis (NCT01383759), a na na study. The primary outcome is Participants Evaluated for Toxicity.

2. Clinical Question

Statistically, the central question is what safety and response information can be obtained from this treatment sequence in the enrolled population. Because the design has no concurrent comparator, observed outcomes can describe the participants who received the regimen but cannot isolate a treatment effect from other explanations. The registry record does not report numerical primary-outcome or efficacy estimates, so the stated questions describe the study’s aims rather than establish what happened to participants.

3. Trial Design

This is a completed, single-group pilot study sponsored by Memorial Sloan Kettering Cancer Center. The registry lists enrollment of 20 participants, allocation as NA, and masking as none. The phase is recorded as NA. The study began on 2011-06-24, had a primary completion date of 2019-04-30, and has completed status.

The treatment sequence begins with bortezomib and dexamethasone, continues with high-dose melphalan and autologous stem cell transplantation, and then includes maintenance bortezomib and dexamethasone. The arm description states that participants receive 1-3 cycles of BD before HDM/ASCT. The registry describes the study as a pilot intended to gain information and estimate toxicity and tolerability in patients with MIDD associated with multiple myeloma and AL amyloidosis.

A single-group design follows participants receiving the study treatment without assigning a separate comparison group. It can document outcomes observed during the study, but it does not provide a randomized estimate of how those outcomes would differ under another treatment. The registry record does not report a separate control regimen, a randomization procedure, or masking of treatment assignment. Allocation is listed as NA, so no allocation process should be inferred beyond the single-group classification.

The registry names a primary toxicity outcome and secondary outcomes covering hematologic response, cardiac and renal organ response, and progression-free survival. It does not report the protocol’s sample-size justification, a detailed statistical analysis plan, interim analyses, or further operational details of follow-up and outcome assessment. Those omissions limit how fully the design can be reconstructed from the registry record.

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

Analysis population for the primary outcome, as defined in the registry: Data were not collected for MIDD group.

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 Participants Evaluated for Toxicity, measured over 2 years.

The primary outcome is titled “Participants Evaluated for Toxicity,” has participants as its unit, and is defined as a count of participants. Its timeframe is 2 years. The description states that toxicities will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

This endpoint captures the number of participants evaluated for toxicity; it is not, by its title alone, a count of participants who experienced a toxicity or a count of toxicity events. That distinction matters because evaluation, occurrence, severity and frequency are different quantities. The registry record does not provide a numerical result for the primary outcome, a breakdown by toxicity grade, or a reported analysis of how many participants experienced specific toxicities under this primary measure.

General: A toxicity endpoint is relevant in a pilot study of a multi-stage treatment because tolerability is one of the study’s stated aims. A standardized grading system can help classify adverse events consistently. However, an endpoint’s usefulness depends on a clear definition of what is counted and on the completeness of assessment. The registry describes the grading standard and the evaluation count, but does not report further details about assessment schedules, attribution to treatment, or how missing toxicity assessments are handled.

The registry also lists secondary outcomes for hematologic response, cardiac and renal organ response at 12 and 24 months, and progression-free survival at 24 months. Those outcomes broaden the study’s stated aims, but the record does not report numerical outcome estimates for them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: Statistical interpretation begins by identifying the design, the population being described, the outcome definition and the kind of estimate reported. These features determine whether a result is descriptive or comparative and what uncertainty it can address. For this study, the registry identifies a single-group pilot, a count-based primary toxicity outcome and a treatment sequence. It does not report a numerical primary-outcome estimate or a detailed statistical analysis plan.

What does a single-group design estimate?

A single-group study can describe outcomes among participants who received the study regimen. For example, an event count can tell readers how many participants in a defined group were recorded as affected, when the registry reports that count and its denominator. Such a description does not estimate a contrast between assigned treatments because there is no concurrent control arm. It also does not separate treatment effects from other possible influences on outcomes.

Randomization is useful in comparative studies because it can balance measured and unmeasured participant characteristics across treatment groups on average. This study is not randomized: allocation is recorded as NA, and the design is single-group. As a result, comparisons with historical experience or other studies would require assumptions about comparability that the registry record does not establish. No such external comparison is reported in the record.

What does a count endpoint mean?

The primary endpoint is a count of participants evaluated for toxicity. A count can be informative about the number of people assessed, but it is not interchangeable with the number experiencing toxicity, the number of distinct events, or the severity distribution. Those quantities answer different questions. The endpoint description specifies assessment according to NCI CTCAE version 4.0, while the registry does not report a numerical result for the count or a more detailed summary of the primary toxicity assessment.

General: A denominator is essential when interpreting a count as a proportion or risk. A count alone does not show how frequently an outcome occurred unless the relevant number of participants at risk or assessed is also defined. A rate also depends on time at risk, and a time-to-event outcome depends on event timing and censoring. The registry lists “Progression Free Survival at 24 Months” as a secondary outcome, but no numerical estimate or analysis details are reported in the record.

How should uncertainty be understood?

General: A confidence interval describes a range of values compatible with the observed data under the assumptions of the analysis method. Wider intervals indicate less precision; narrower intervals indicate greater precision. An interval does not guarantee that the underlying value lies within its endpoints, and it does not remove bias caused by the design or measurement. The registry record does not report confidence intervals for the primary outcome, adverse-event entries or listed secondary outcomes.

General: Hypothesis tests address a specified statistical null hypothesis under model assumptions. A p-value is not the probability that a treatment works, nor does a small p-value establish clinical importance. In a single-group study, a test would need a defined reference or model to answer a comparative question. The registry record reports no analyses and does not give a hypothesis-testing plan or test results for the outcomes described.

Why do event definitions and denominators matter?

For adverse events, readers need to know what counts as an event, whether the count refers to affected participants or events, the period of observation, and the denominator used for any percentage. Serious adverse events and other adverse events are separate registry categories, but their full operational definitions and potential overlap are not reported in the record. The listed percentages for individual serious-event terms should therefore be interpreted cautiously because the denominator and event-count basis are not stated.

General: Over-dispersion occurs when event counts vary more than a simple statistical model expects. It can arise when participants differ in their underlying event rates or when repeated events cluster within some participants. A model that ignores this extra variability may understate uncertainty. This is a general consideration for count outcomes; the registry record does not report a count model, an over-dispersion assessment or repeated-event analyses for this study.

What can a pilot study establish?

A pilot study can gather preliminary information about feasibility, tolerability and outcome measurement. The arm description specifically frames the study as a pilot to gain information and estimate toxicity and tolerability. A pilot’s observed results may help describe the enrolled group, but a small single-group study does not automatically provide a precise comparative treatment effect. The registry record does not report a sample-size justification, so the reason for the enrollment target is not established by the record.

General: Power is the probability that a planned statistical test will reject a null hypothesis under a specified alternative, given a model and design. It is a planning concept, not a property that can be read directly from an observed result. A planning sample size depends on assumptions such as the target effect, variability, significance level, allocation and analysis method. The record does not report the study’s own sample-size justification or a detailed analysis plan; no claim about the trial’s planned or achieved power follows from the enrollment count alone.

General: Recalculation from posted summary statistics, when available, can serve as a simple unadjusted check but may differ from a sponsor’s prespecified analysis if methods or populations differ. No recalculated outcome estimates are reported in the registry record for this study. Accordingly, there is no numerical recalculation to interpret or compare with a sponsor analysis.

The secondary outcomes identify clinical domains and assessment timepoints, but outcome names alone do not specify statistical methods. The record does not report how response categories were defined, how progression-free survival was estimated, what censoring rules applied, or whether analyses were adjusted for participant characteristics. Those details would be needed to assess model assumptions and interpret the precision of outcome estimates.

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("Amyloidosis", "Monoclonal Ig DepositionDisease (MIDD)")
n      <- c(19, 1)
events <- c(19, 1)
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  Amyloidosis  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9
ARM  Monoclonal Ig DepositionDisease (MIDD)  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary toxicity outcome and lists secondary outcomes for hematologic response, cardiac involvement at 12 and 24 months, renal involvement at 12 and 24 months, and progression-free survival at 24 months. It records 8 outcome measures. The record does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment to account for testing multiple hypotheses.

General: When several outcomes are tested, the chance of at least one apparently noteworthy result can increase if each is assessed separately without accounting for the collection of tests. A prespecified hierarchy or multiplicity adjustment can help define how evidence across outcomes should be interpreted. The existence, details and consequences of such a strategy for this study are not reported in the registry record.

Missing-data methods are also not reported in the registry record. The record does not describe how incomplete toxicity assessments, unavailable follow-up, or missing response measurements were handled. It does not state whether analyses used all enrolled participants, only participants with an assessment, or another analysis population. The primary outcome title indicates participants evaluated for toxicity, but does not establish how participants without an evaluation were treated in any analysis.

General: Missingness can affect interpretation when participants with unavailable measurements differ from those with observed measurements. Complete-case summaries describe those with recorded data and may not represent all enrolled participants if missingness is related to outcome or participant characteristics. Methods such as imputation or sensitivity analysis require assumptions that should be stated; the registry record does not report whether any were used.

The record also does not report interim analyses, stopping rules, or a detailed statistical analysis plan. These omissions do not show that such procedures were or were not used; they mean that the registry record does not document them. Without outcome estimates and analysis details, multiplicity, missing-data handling and analysis-population choices cannot be evaluated for their impact on results.

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: hip fracture (100.0%), upper gastrointestinal hemorrhage (100.0%), hypotension (21.1%), acute kidney injury (15.8%), syncope (10.5%).

The registry lists serious adverse events and other adverse events separately by condition group. For amyloidosis, it records 19 at risk and 17 affected for serious adverse events, 19 at risk and 19 affected for other adverse events, and 7 deaths. For MIDD, it records 1 at risk and 1 affected for serious adverse events, 1 at risk and 1 affected for other adverse events, and 0 deaths. These are the registry’s reported counts; they should not be combined into a treatment comparison.

The listed serious-event terms and percentages are hip fracture, 100.0%; upper gastrointestinal hemorrhage, 100.0%; hypotension, 21.1%; acute kidney injury, 15.8%; syncope, 10.5%; and dehydration, 10.5%. The registry record does not state the denominator or whether these percentages refer to affected participants, events, or another basis. They should not be read as incidence estimates without that information. The record also does not explain whether participants could contribute to more than one term, or how these terms relate to the separate group counts.

General: Seriousness is a classification of an adverse event, not a measure of how likely an event is to occur or how strongly it is attributable to treatment. Event counts can describe what was recorded, but interpretation of risk requires clear definitions, denominators and follow-up. The listed counts do not establish that the treatment caused an event.

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

The registry record describes a completed pilot study of a multi-stage regimen: BD, followed by HDM/ASCT and maintenance BD. It documents a single-group design, enrollment of 20 participants, a toxicity-focused primary outcome and a set of secondary outcomes. The adverse-event entries provide counts for the listed condition groups. These details show what the study was designed to examine and what safety summaries the registry records.

They do not establish a comparative treatment effect. There is no concurrent control group, and the record does not report randomized allocation. Therefore, the observed counts cannot show how outcomes would have differed under another treatment. The treatment sequence also includes multiple components, so a single-group summary cannot identify the separate contribution of BD before transplantation, transplantation itself, or maintenance BD.

The primary outcome is the number of participants evaluated for toxicity, not a reported count of participants who experienced toxicity. Although serious and other adverse event counts appear in the registry, the detailed event definitions, percentage denominators and analysis methods are not reported. The listed secondary outcomes indicate intended assessments, but the record does not report numerical estimates for hematologic response, cardiac or renal response, or progression-free survival.

General: Statistical evidence is strongest when the outcome definition, analysis population, missing-data approach and uncertainty estimates are transparent. Without those details, readers cannot determine the precision of estimates or assess how sensitive they might be to analysis choices. In a pilot study, descriptive information may be useful for characterizing the enrolled participants and recorded events, while remaining insufficient for firm comparative conclusions.

The study’s completion status is an administrative status, not a result. Similarly, the study description’s stated aim to assess toxicity and efficacy does not itself answer whether an outcome occurred at a particular frequency or whether the regimen changed it. Conclusions should be confined to the design and registry entries actually reported. The record does not support a claim that the treatment is effective or ineffective, nor a causal interpretation of the adverse events.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between an outcome aim and an outcome result. The registry describes a toxicity-focused primary endpoint and names several response and progression outcomes, but does not report numerical estimates for those outcomes. The design and endpoint definitions can therefore be assessed, while estimates of magnitude and precision cannot be evaluated from the registry record.

The single-group structure is central to interpretation. It permits descriptive reporting for participants who received the regimen, but offers no randomized control against which to estimate a treatment contrast. This distinction is important when a study description uses language about efficacy: a stated objective is not the same as a demonstrated comparative effect. The design limits causal interpretation regardless of whether a descriptive event count is large or small.

The primary endpoint also illustrates why measurement wording matters. “Participants Evaluated for Toxicity” counts evaluation, while readers may naturally look for the number of participants experiencing toxicity. Those are not the same measure. Clear reporting of assessed participants, affected participants, event counts, severity and follow-up would make the safety profile easier to interpret. The registry supplies some adverse-event counts by condition group but does not report all of those details.

General: Pilot studies can contribute early information about tolerability, outcome definitions and the practical conduct of a treatment sequence. Their value does not depend on producing a definitive comparative answer. However, a pilot’s scope should be reflected in the strength of conclusions, and precision is especially important when event counts are limited. Confidence intervals and transparent analysis populations would help readers judge how much uncertainty remains.

The registry’s record of missing analysis details is also a useful reminder that outcome names do not reveal how outcomes were analyzed. Definitions, follow-up, missingness, multiplicity and statistical methods all affect interpretation. For biostatisticians and clinical researchers, the main lesson is to separate what the design can estimate from what the study aimed to investigate, then distinguish both from numerical results actually reported.

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 principal limitation for interpretation is the single-group design. Without a concurrent comparator, the registry record cannot support a randomized treatment contrast or separate treatment effects from other influences. Allocation is recorded as NA, masking as none, and the study model as single-group. No control regimen or randomization process is described.

The registry lists enrollment of 20 participants, but does not report a sample-size justification. The record also does not report a detailed statistical analysis plan, interim analyses, stopping rules, confidence intervals, hypothesis tests or adjusted estimates. It is therefore not possible to assess planned precision, prespecified modeling choices or the role of any interim monitoring from the record.

The primary endpoint is described as participants evaluated for toxicity. The record does not provide its numerical result or explain how participants without an assessment were handled. It also does not report a detailed analysis population, missing-data strategy, toxicity-assessment schedule or attribution method. For the listed serious-event percentages, the denominator and event-count basis are not stated. The relationship between individual event terms and the broader adverse-event counts is also not described.

Secondary outcomes are named, with cardiac and renal involvement assessed at specified timepoints and progression-free survival at 24 months. The record does not report numerical estimates, detailed response definitions, censoring rules, follow-up completeness or methods for handling multiple outcomes. These omissions limit assessment of both the results and the assumptions behind any potential analysis.

General: These limitations describe what the registry record does not document; they do not establish that a procedure was absent from the full study protocol or analysis. Conclusions should therefore be restricted to the information recorded rather than extended to undocumented methods or outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis — NCT01383759.
• Registry record last updated 2020-04-07; status last verified 2019-04.
• Results first posted 2020-03-30.
• 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

NCT01383759 is a completed pilot study sponsored by Memorial Sloan Kettering Cancer Center. The study began on 2011-06-24, had a primary completion date of 2019-04-30, and records enrollment of 20 participants. The phase is NA. The design is single-group, allocation is NA, and masking is none.

The regimen consists of bortezomib and dexamethasone, followed by high-dose melphalan and autologous stem cell transplantation, then maintenance bortezomib and dexamethasone. The arm description specifies 1-3 cycles of BD before HDM/ASCT. The primary outcome is participants evaluated for toxicity over 2 years using NCI CTCAE version 4.0.

Secondary outcomes include hematologic response, cardiac and renal organ response at 12 and 24 months, and progression-free survival at 24 months. The registry record lists adverse-event counts by condition group, but does not report numerical estimates for the primary or listed efficacy-related outcomes, or a detailed statistical analysis plan.