Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma (NCT02043860), a na phase 1 study. The primary outcome is Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze.

2. Clinical Question

The clinical question therefore combines a dose-escalation objective with an outcome objective. The study description says TMI dose would increase from the lowest planned dose until the maximum tolerated dose (MTD) was reached. The registry record does not report that an MTD was identified, and the posted outcome record does not provide PFS estimates. These aims should be distinguished: an escalation study can assess dose-related tolerability, while PFS describes the time until a disease-related event under a specified outcome definition. Neither a dose comparison nor a PFS comparison can be inferred from these registry results.

3. Trial Design

This was a phase I trial sponsored by the University of Illinois Chicago. Its design is listed as single group, with no masking and allocation recorded as NA. The registry describes a conventional 3+3 dose-escalation approach: patients would receive TMI with standard high-dose melphalan before autologous stem cell rescue, with planned TMI dose levels of 3Gy, 6Gy, 9Gy, or 12Gy. The stated purpose of escalation was to reach the maximum tolerated dose. The record does not report a completed escalation sequence or an MTD.

The registry lists enrollment as 3 and the status as terminated. The recorded start date is 2014-01-10, and the primary completion date is 2016-11-07. The posted safety cohort is titled “Cohort 1 TMI Dose 3Gy.” Its serious-event counts are reported for 2 participants at risk. The registry does not show safety cohorts at the higher planned doses. These registry entries do not establish why the study ended or whether all participants enrolled received the same treatment; that detail is not reported in the registry record.

Because there is no separate control group, the study cannot provide a randomized or concurrent comparison of TMI plus melphalan against melphalan alone. Likewise, the escalating dose levels are intended as part of the study design, not as independent randomized treatment groups. The registry does not report the dose-allocation decisions for each participant, the criteria used to move between dose levels, or a statistical analysis plan. The posted primary outcome is PFS up to 1 year post-transplant, but its record states that data were not collected and gives no analysis.

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 not collected

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 Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze, measured over Up to 1 year post-transplant..

Progression-free survival (PFS) is the stated primary endpoint, with a timeframe of up to 1 year post-transplant. In general, PFS is a time-to-event measure intended to capture how long participants remain alive without disease progression. It is used in clinical research because it incorporates both the timing and occurrence of an outcome, rather than reporting only a single status at a particular visit. The registry description does not give the operational definition of progression, the method for confirming it, or details about how deaths and censoring were handled.

For this trial, the registry gives no PFS estimate, event count, confidence interval, or analysis. Its outcome title states that there were no results because 1 subject came off treatment within 7 days and 1 subject came off treatment within 5 days, leaving not enough data to analyze; the population is also recorded as “Data not collected.” Thus, the endpoint was planned but the posted record does not quantify PFS or its precision. The intended timeframe alone does not indicate that follow-up was completed or that a PFS result can be estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

This trial is categorized as phase I and single group. In general, phase I research is often focused on initial evaluation of a treatment approach, including dose and tolerability, rather than on a definitive comparative estimate of clinical benefit. The registry's summary specifically describes a 3+3 dose-escalation approach for TMI added to high-dose melphalan before autologous stem cell rescue. It names planned TMI levels of 3Gy, 6Gy, 9Gy, and 12Gy, with the stated aim of reaching the maximum tolerated dose. The record does not describe the escalation rules in enough detail to reconstruct decisions, and it does not report an MTD.

In a dose-escalation design, sequential cohorts can be used to guide whether a dose is retained or whether escalation proceeds. Such a design is not the same as random assignment among dose groups. Here, allocation is listed as NA and the model is single group; masking is listed as none. The registry does not report a randomization procedure, a masking procedure, or a concurrent control. Consequently, differences between dose cohorts, if any, would not automatically have the interpretation of randomized treatment effects. The available registry record does not provide a dose-by-dose efficacy analysis.

The primary endpoint is PFS up to 1 year post-transplant. Generally, time-to-event methods are used when outcomes have both an event component and a time component, and when some participants may not have an observed event before follow-up ends. A survival curve can describe the estimated probability of remaining event-free over time; a confidence interval communicates uncertainty around an estimate. These are general statistical concepts, not results from this trial. The registry gives no PFS curve, estimate, confidence interval, event count, or analysis. It also does not specify the operational definition of progression, the censoring rules, or the handling of death for this endpoint.

For time-to-event outcomes, the amount and timing of follow-up are important to interpretation. Participants who do not experience an event during observation may contribute information up to their last known follow-up, depending on the analysis plan. If follow-up is limited or outcome data are not collected, a meaningful estimate may not be possible. In this record, the primary outcome says “Data not collected” and reports that 1 subject came off treatment within 7 days and 1 subject came off treatment within 5 days, with not enough data to analyze. The record does not provide the later follow-up status needed to assess whether any participants contributed endpoint information after those events.

General statistical comparisons require a clearly defined estimand, outcome, analysis population, and method. An estimand specifies the treatment effect or outcome quantity of interest, the population, and how events such as treatment discontinuation are handled. The registry does not provide such details for PFS. It also does not report a model, adjusted analysis, or prespecified handling of missing outcomes. With a single group and no posted PFS result, there is no treatment contrast to estimate from this record.

Over-dispersion is a general issue for count outcomes: observed variability can exceed the variability assumed by a simple count model, which can make standard errors and uncertainty intervals too small if the model is not appropriate. Nothing in the registry record indicates that an over-dispersion analysis was conducted, and no count model or count outcome analysis is posted. This concept therefore does not explain or alter the reported PFS status; it is relevant only as a general consideration when analyzing count data.

Planning calculations are distinct from trial observations. The registry's planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumptions also distinguish total event counts for time-to-event outcomes from participants per arm for other outcomes. Those are planning conventions, not observed trial findings or a measure of observed power. Because this study is single group and no PFS effect estimate is posted, such planning assumptions cannot supply a treatment-effect estimate for this trial or establish the precision of its missing PFS result.

Finally, statistical significance and clinical interpretation are not interchangeable. In general, a p-value addresses compatibility of observed data with a specified statistical model and null hypothesis; a confidence interval describes a range of estimates compatible with the data and assumptions. Neither can be read from this registry record for PFS because no analysis is reported. The absence of a reported p-value does not mean that a test was negative; the record states that there were not enough data to analyze.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and reports no analyses. The record does not report a multiplicity strategy, such as adjustment across multiple primary endpoints or across a family of statistical tests. Since no PFS analysis is posted, there are no reported tests whose multiplicity adjustment can be evaluated. The absence of a stated adjustment should not be read as evidence that a particular method was used or that the analysis was prespecified.

Missingness is especially consequential for the primary endpoint. The PFS outcome population is recorded as “Data not collected,” and the title states that there were no results because 1 subject came off treatment within 7 days and 1 subject came off treatment within 5 days, leaving not enough data to analyze. The registry does not report an analysis population, participant-level follow-up, missing-data assumptions, imputation method, or sensitivity analysis. It is therefore not possible to determine whether missing outcome information was related to prognosis, treatment discontinuation, or another factor.

In general, an analysis population describes which participants contribute to a particular estimate and how events such as discontinuation are handled. The registry does not specify an intention-to-treat, per-protocol, or safety population for the posted PFS outcome. Although enrollment is recorded as 3 and safety counts are posted for 2 participants at risk in the 3Gy cohort, those details do not define the PFS analysis population. The record does not provide enough detail to reconcile enrollment, treatment exposure, and endpoint follow-up.

These omissions limit both the interpretation of missing data and the reproducibility of any analysis. No assumptions about unobserved PFS outcomes can be justified from the registry record alone.

11. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures are counts for the registry cohort titled “Cohort 1 TMI Dose 3Gy.” The record lists 2 participants at risk for serious adverse events and 0 affected. It lists 2 participants at risk for other adverse events and 2 affected. Deaths are recorded as 0. These categories should be read separately: the count for other adverse events is not the serious-event count.

The serious adverse-event terms list is empty, and no specific other adverse-event terms are provided. The record does not describe severity grades, event timing, duration, relatedness to treatment, or how events were collected. Therefore, the figures do not identify what the other adverse events were or whether they were considered treatment-related. They also cover the posted 3Gy cohort, not all planned dose levels.

In general, safety counts describe observed events in a defined group; they do not by themselves establish the frequency of events in a broader population or support a comparison with another regimen. With this limited cohort information and no control group, the registry figures should be treated as descriptive counts, not as comparative evidence.

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

The registry record documents a phase I study of TMI added to high-dose melphalan before autologous transplant for multiple myeloma. It describes planned escalation through 3Gy, 6Gy, 9Gy, and 12Gy and identifies PFS up to 1 year post-transplant as the primary outcome. The posted record also reports enrollment of 3, terminated status, and safety counts for a 3Gy cohort. These are the findings that can be stated from the registry record.

The record does not provide an analyzable PFS result, an estimate of the maximum tolerated dose, or an efficacy comparison. It explicitly states that there were no PFS results because 1 subject came off treatment within 7 days and 1 subject came off treatment within 5 days, and that there was not enough data to analyze. The population is listed as “Data not collected.” Thus, the primary outcome cannot be used to estimate the time participants remained progression-free or to assess the uncertainty of such an estimate.

These results do not establish whether the combined treatment improved, worsened, or had no effect on PFS. They also do not show whether TMI at any dose was better or worse than melphalan conditioning alone, because no concurrent control group is recorded. The safety figures do not establish an overall safety profile across the planned doses: they are limited to the posted 3Gy cohort, include no serious adverse events among 2 participants at risk, and list 2 participants at risk with other adverse events. Specific event descriptions are not given.

In general, a small or incomplete dataset can leave substantial uncertainty, but no precision estimate is available to quantify that uncertainty for PFS. Nor should the lack of a statistical result be translated into a negative finding. It reflects the absence of an analyzable endpoint result in the registry record. No conclusion about clinical benefit, harm, or dose selection follows from these data alone.

13. Why This Trial Matters Statistically

This record illustrates an important distinction in clinical-trial reporting: a stated endpoint and a planned design do not guarantee an analyzable outcome. PFS was identified as the primary outcome, with a timeframe up to 1 year post-transplant, but the record says data were not collected and no results could be analyzed. For readers, this means the planned question is visible while its quantitative answer is not.

The trial also highlights the difference between dose escalation and comparative evaluation. The summary describes a 3+3 escalation plan across specified TMI dose levels, but the study is single group and has no concurrent control. A dose-escalation objective does not by itself produce a comparative estimate of the effect of TMI, and a listed dose sequence should not be mistaken for evidence that every level was administered or evaluated. The registry does not report an MTD.

Statistically, the absence of an endpoint estimate limits more than conclusions about significance. There is no PFS effect size, uncertainty interval, event count, or analysis population to assess. Without those elements, readers cannot judge the stability or precision of an outcome estimate or reproduce an analysis. The posted safety counts are also narrow in scope: they describe the 3Gy cohort and do not characterize the planned dose range.

The record is therefore useful as an example of how registry entries can document design intent and limited safety information while leaving the primary clinical outcome unavailable. Interpreting that distinction carefully prevents study aims from being mistaken for observed results.

14. Limitations

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

The primary limitation is the lack of an analyzable PFS outcome. The registry says the population was “Data not collected” and gives no event count, follow-up summary, estimate, or uncertainty interval. Its outcome title attributes the absence of results to 1 subject coming off treatment within 7 days and 1 subject coming off treatment within 5 days, with not enough data to analyze. The reasons for these departures and subsequent outcome status are not reported in the registry record.

Enrollment is recorded as 3, but the registry does not provide participant-level accounting for enrollment, treatment received, dose level, or PFS follow-up. The posted safety cohort is at 3Gy, with 2 participants at risk for each adverse-event category. No higher-dose safety cohort is shown in the record. The trial is marked terminated, but the reason for termination is not reported in the registry record.

The single-group design limits comparative interpretation. There is no separate control group, and the record does not report randomized dose assignment. Consequently, there is no basis for estimating a comparative treatment effect against melphalan alone or another regimen. Nor does the record establish whether dose escalation reached the planned higher levels or identified an MTD.

Further details needed to assess the planned analysis are not reported in the registry record, including the PFS event definition, censoring approach, analysis population, missing-data handling, and statistical analysis plan. The safety information lacks specific event terms and detail on severity, timing, and relatedness. These omissions prevent fuller assessment of both endpoint methods and the clinical meaning of the safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma — NCT02043860.
• Registry record last updated 2019-10-14; status last verified 2019-09.
• Results first posted 2019-10-14.
• 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.

18. Record Summary

NCT02043860 is a phase I, single-group trial of total marrow irradiation with high-dose melphalan before autologous transplant for multiple myeloma. The registry describes planned TMI escalation at 3Gy, 6Gy, 9Gy, and 12Gy, lists enrollment of 3, and records the study status as terminated. The sponsor is University of Illinois Chicago.

The primary outcome was PFS up to 1 year post-transplant. The registry reports no PFS results, says data were not collected, and states there was not enough data to analyze after 1 subject came off treatment within 7 days and 1 within 5 days. Safety counts are reported for a 3Gy cohort: 0 serious adverse events among 2 at risk, 2 other adverse events among 2 at risk, and 0 deaths. No comparative outcome estimate or MTD is reported.