This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment (NCT01548573), a na phase 2 study. The primary outcome is Event-Free Survival (EFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01548573 |
| Phase | Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Iowa |
| Results posted | Yes |
2. Clinical Question
The study asked whether a treatment program incorporating tandem autologous stem cell transplantation and additional drug therapy could increase event-free survival (EFS) for people with multiple myeloma who had received less than 12 months of preceding therapy. The registry describes a planned comparison with Total Therapy II, with a goal of increasing median EFS from 4.8 years to 7.2 years. It also describes an aim to reduce toxicity by lowering the intensity of induction, consolidation, and maintenance therapy while adding drugs intended to address drug resistance.
Population
Participants with multiple myeloma and less than 12 months of preceding therapy. The registry lists enrollment of 19 participants. It does not report further eligibility details in the available record.
Intervention
A single-group program centered on tandem autologous stem cell transplantation, with listed drugs including dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide, bortezomib, and thalidomide. The registry description also names DPACE induction chemotherapy and stem cell collection.
Comparator
There was no concurrent comparison arm. The stated reference was Total Therapy II, so the planned comparison was historical rather than a randomized, like-for-like comparison within this trial.
Primary question
Could the treatment program increase median EFS, with the registry describing a target change from 4.8 years to 7.2 years? The registry says the primary outcome data were not collected, so this question cannot be answered from the posted primary outcome results.
The registry also describes an optional biospecimen sub-study focused on gene expression profiling and drug resistance. That exploratory aim is separate from the primary EFS question. The record does not report results for it.
3. Trial Design
This was a phase 2, single-group study with no masking and no randomized allocation. The registry lists 19 participants enrolled and a status of terminated. The listed start was 2012-05, and primary completion was 2013-07. Those dates describe the registry record; they do not establish how long each participant was followed.
The treatment arm is described as tandem autologous stem cell transplantation. The available regimen description names DPACE induction—dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide—along with stem cell collection. It says that additional collection and/or chemotherapy might be required, and that participants would receive dexamethasone after collection. The registry lists bortezomib and thalidomide among the interventions as well. The full schedule and details of all treatment phases are not reported in the registry record.
The planned endpoint timeframe was 8 years. The primary outcome description says the intent was to assess EFS against Total Therapy II, but the comparator was not an arm enrolled alongside participants in this study. Without a concurrent control group, comparisons with historical results can be affected by differences in populations, care, follow-up, and outcome assessment. The registry does not report a method for adjusting such differences.
The record states that enrollment halted prematurely because the study met a stopping rule: 3 or more of the first 20 participants died due to treatment-related toxicity. The listed enrollment is 19, and the adverse-event record lists 3 deaths. The record does not provide additional detail about the timing or review process behind the stopping decision. The treatment program and its historical comparison therefore need to be distinguished from a controlled estimate of treatment effect.
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
| Stage | Tandem Transplant in MM <12 Mos of Prior Treatment |
|---|---|
| STARTED | 19 |
| COMPLETED | 14 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Tandem Transplant in MM <12 Mos of Prior Treatment |
|---|---|
| Death | 3 |
| Withdrawal by Subject | 2 |
Analysis population for the primary outcome, as defined in the registry: Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity). Data for outcome measure 1 were 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.
| Characteristic | Unit | Tandem Transplant in MM <12 Mos of Prior Treatment |
|---|---|---|
| Participants analysed | 19 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 16 |
| Age, Categorical: >=65 years | Participants | 3 |
| Age, Continuous | years | 59.4 (49 to 70.6) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 11 |
| Region of Enrollment: United States | participants | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Event-Free Survival (EFS), measured over 8 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was event-free survival (EFS), with a stated timeframe of 8 years. In general, an event-free survival endpoint measures the time participants remain free of a prespecified event or events. The time-based measure can describe both whether an event occurred and when it occurred, rather than only counting events at a single visit. The particular events included in this study's EFS definition are not reported in the registry record, so the endpoint components cannot be specified more precisely.
The registry's stated aim was to compare median EFS with Total Therapy II. A median is the time by which half of the relevant participants have experienced the endpoint event, under the endpoint definition and analysis approach. The registry describes a target increase from 4.8 years to 7.2 years. These values are part of the study objective, not results observed in the enrolled participants.
EFS is used in general when the timing of disease-related or other specified events is relevant to the research question. Its interpretation depends on a clear event definition, follow-up, and appropriate handling of participants whose event status is unknown at the end of observation. Those details, including the EFS event definition and analysis, are not reported in the registry record. Most importantly, the registry states that primary outcome data were not collected. There is therefore no posted participant-level EFS result from which to estimate a median or compare outcomes with the stated historical reference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the primary EFS outcome was not collected. The registry describes a planned EFS question and its target comparison, but it does not report an EFS estimate for the 19 enrolled participants. There is consequently no posted median EFS, survival curve, confidence interval, or test result for the primary outcome. The stated change from 4.8 years to 7.2 years is a goal in the outcome description, not evidence that the change occurred.
The trial was single-group and had no concurrent control arm. Its stated reference, Total Therapy II, is historical. Even if this record had included an EFS estimate, a historical comparison would not have the same basis as a randomized comparison conducted in the same period and under the same procedures. Differences in participant characteristics, treatment delivery, follow-up, and outcome definitions can affect such comparisons. The registry record does not report adjustments or other methods intended to address those sources of difference.
Enrollment was halted prematurely under the stated stopping rule concerning treatment-related deaths. The record lists 3 deaths and says the study met its stopping rule of 3 or more deaths due to treatment-related toxicity among the first 20 participants. This is important context for understanding why enrollment halted. It does not supply an EFS analysis, nor does it describe the timing of deaths relative to the EFS endpoint or provide a complete account of causes and adjudication.
The safety record lists 13 participants with serious adverse events and 19 with other adverse events, among 19 participants at risk in each category. It also lists 3 deaths. These summaries describe reported safety data, but they do not estimate comparative risk: no control group is present. The listed serious-event terms and their percentages should be read as registry reports, not as a complete account of event severity, duration, attribution, or clinical course.
The registry reports zero analyses and states that primary outcome data were not collected. The record therefore does not support a statistical conclusion about the planned EFS target. It also does not establish whether the intended reduction in toxicity was achieved. The available evidence describes the design, early termination, and reported safety events; it does not quantify a treatment effect on EFS or establish a causal comparison with Total Therapy II.
Any sample-size planning illustrations associated with these results are planning calculations, not observed power. In general, such calculations depend on assumptions about the effect to detect and the analysis design. They cannot replace outcome data or resolve the absence of an EFS estimate. No additional inference should be drawn from the target values alone.
9. Statistical Methods Explained
Study structure. The registry identifies the study as phase 2, single-group, with allocation listed as not applicable and masking listed as none. In general, a single-group study describes outcomes under a treatment program without a concurrent control arm. It can document what was observed among enrolled participants, but by itself it cannot separate treatment effects from other explanations for those outcomes. Here, that distinction matters because the registry's planned EFS reference was Total Therapy II, not a concurrently enrolled comparison group.
Time-to-event endpoints. EFS is a time-to-event outcome. In general, time-to-event methods use both the event status and follow-up time, and can account for participants who have not experienced the event by the last known observation through censoring. Censoring means that the event time is not observed during the available follow-up; it does not establish that the participant will never experience the event. The interpretation depends on the event definition, the censoring rules, and the assumptions used in analysis. The EFS event components, censoring rules, and analysis method are not reported in the registry record. The primary outcome data were not collected, so these methods cannot be evaluated from a posted EFS analysis.
A median time-to-event estimate is a summary of the time distribution. A confidence interval, in general, describes the statistical uncertainty around an estimate under the specified model and assumptions. Neither a median EFS estimate nor its confidence interval is reported for the enrolled participants. The target values in the outcome description—4.8 years and 7.2 years—are the stated comparison goal, not calculated trial results. No p-value or other inferential estimate for EFS is reported.
Historical comparison. A comparison against an earlier study is not equivalent to a randomized comparison. Random assignment, in general, helps make treatment groups comparable with respect to measured and unmeasured factors, while a historical comparison may differ in population, eligibility, care practices, observation periods, and outcome ascertainment. These differences can make an apparent contrast difficult to attribute to the treatment program. The registry does not report a statistical adjustment strategy for the Total Therapy II comparison. It also does not report details sufficient to assess whether the historical endpoint definition and follow-up matched the planned EFS assessment.
Stopping rule and inference. The record says enrollment halted because the stopping rule was met: 3 or more of the first 20 participants died due to treatment-related toxicity. A stopping rule is a prespecified or otherwise applied condition for ending enrollment or treatment; its statistical interpretation depends on the rule's design, monitoring schedule, and decision process. The registry does not report those procedural details or an interim analysis plan. The stated rule is a reason for early termination, not a statistical estimate of EFS or a comparison of treatment effects.
Safety summaries. The adverse-event record reports counts of participants at risk and affected, along with selected serious-event terms and percentages. A participant count is not the same as an event count: one participant may experience more than one event, and the record does not provide event-level totals for each term. General comparisons of adverse-event risk would require comparable groups, definitions, observation windows, and attribution procedures. This study has no concurrent comparator, and the registry does not report those additional details. The listed summaries should therefore be read descriptively.
Planning calculations. In general, sample-size planning estimates how many participants or events would be required under chosen assumptions to detect a specified effect with a chosen significance level and power. The planning illustrations described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect is framed as a stated fraction of an observed effect. For time-to-event outcomes, the illustration is expressed in total events, while other outcomes are expressed as participants per arm. These are planning assumptions, not the design of this single-group study, and are not observed power. The registry does not report the trial's own sample-size justification. Because primary EFS data were not collected, a planning illustration must not be interpreted as an estimate of this study's EFS effect or as evidence that the target was reached.
Analysis reporting. The registry lists no reported analyses. It does not report an EFS model, an estimate of treatment effect, uncertainty intervals, hypothesis tests, or an adjustment strategy. It also does not report whether any statistical analyses were conducted outside the registry. The absence of a posted analysis limits what can be concluded: a treatment objective and a stopping rule do not substitute for analyzed outcome data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures, but the available record does not report a multiplicity strategy. In general, when several outcomes or statistical tests are considered, the chance of at least one apparently unusual result can increase if each is assessed separately. Methods for addressing multiplicity depend on which outcomes and tests were planned, their priority, and the inferential claims intended. Those details are not reported in the registry record. Since no analyses are listed, there are no posted test results from which to assess how multiplicity was handled.
Missing-data methods are also not reported in the registry record. The primary EFS outcome is explicitly described as not collected, which is more consequential than ordinary loss to follow-up: there is no posted primary endpoint dataset or estimate to interpret. The record does not describe whether other outcome data were incomplete, how missing observations were defined, or whether any imputation or sensitivity analysis was used. These issues cannot be resolved by assuming a conventional method.
The primary outcome description refers to an intent-to-treat analysis. In general, an intent-to-treat approach analyzes participants according to their assigned group, regardless of subsequent treatment received. This study is single-group, and the registry does not report an analysis population or an analyzed participant set. Enrollment of 19 participants does not by itself establish which participants would have been included in any outcome analysis.
The record says enrollment stopped early under a treatment-related toxicity rule, but it does not describe interim monitoring methods, statistical stopping boundaries, or any resulting adjustment to inferential testing. Those details are not reported in the registry record. With no reported analyses and no collected primary outcome data, multiplicity, missingness, and analysis-population decisions cannot be evaluated for their effect on an EFS estimate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tandem Transplant in MM <12 Mos of Prior Treatment | 13 | 19 | 68.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tandem Transplant in MM <12 Mos of Prior Treatment | 3 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tandem Transplant in MM <12 Mos of Prior Treatment | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Tandem Transplant in MM <12 Mos of Prior Treatment |
|---|---|---|
| Fever | General disorders | 3 of 19 |
| Fever | General disorders | 2 of 19 |
| Neutropenic fever | General disorders | 2 of 19 |
| Atrial Fibrillation with RVR | Cardiac disorders | 2 of 19 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 19 |
| Cholecystitis | Gastrointestinal disorders | 1 of 19 |
| Stoke secondary to cardio-embolism | Nervous system disorders | 1 of 19 |
| Sepsis | Infections and infestations | 1 of 19 |
| Chest pain, air embolism | Cardiac disorders | 1 of 19 |
| Bone pain | Musculoskeletal and connective tissue disorders | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tandem Transplant in MM <12 Mos of Prior Treatment |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 19 of 19 |
| Lymphocyte count decreased | Investigations | 19 of 19 |
| Platelet count decreased | Investigations | 19 of 19 |
| WBC decreased | Investigations | 19 of 19 |
| Hypocalcemia | Metabolism and nutrition disorders | 18 of 19 |
| Hypophosphatemia | Metabolism and nutrition disorders | 16 of 19 |
| Fatigue | General disorders | 13 of 19 |
| Hypokalemia | Metabolism and nutrition disorders | 12 of 19 |
| Nausea | Gastrointestinal disorders | 11 of 19 |
| Diarrhea | Gastrointestinal disorders | 10 of 19 |
Serious events with the highest arm-level rate: fever (15.8%), neutropenic fever (10.5%), atrial fibrillation with rvr (10.5%), pneumonia (5.3%), cholecystitis (5.3%).
The adverse-event record lists 19 participants at risk for serious adverse events, of whom 13 were affected. It lists 19 participants at risk for other adverse events, with 19 affected, and records 3 deaths. These counts describe participants in the study group; they are not a comparison of risks between treatments. No concurrent control arm is reported.
The most frequently listed serious-event terms are Fever (15.8%), Neutropenic fever (10.5%), and Atrial Fibrillation with RVR (10.5%). The record also lists Pneumonia (5.3%), Cholecystitis (5.3%), and Stoke secondary to cardio-embolism (5.3%). These percentages are registry summaries. They do not provide event counts by term, and a participant may have experienced more than one event. The registry does not report the observation period or additional details such as event duration and severity for each listed term.
The record states that enrollment halted because the study met a stopping rule involving 3 or more treatment-related deaths among the first 20 participants. It separately lists 3 deaths in the adverse-event summary. The available information does not establish a comparative rate or allow a causal contrast with another treatment. The figures should be read as descriptive safety information within a prematurely halted, single-group study.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 2, single-group study of tandem autologous transplantation enrolled 19 participants and was terminated after enrollment halted under a stated treatment-related toxicity stopping rule. It also documents that the registry's primary EFS data were not collected and that no analyses are listed. These registry entries are central to interpreting the study: there is no posted EFS result with which to assess the stated target.
The objective describes a median EFS comparison with Total Therapy II, from 4.8 years to 7.2 years. Those values express the intended comparison; they are not estimates from the enrolled group. There is no basis in the posted primary outcome information for concluding that the target was met, missed, or approached. Nor is there a reported confidence interval or test that would show the precision of an EFS estimate.
The study also cannot establish a comparative effect on safety. The adverse-event summaries describe events among enrolled participants, while the study has no concurrent control arm. The listed counts and percentages are relevant to the record's safety description, but they do not quantify how outcomes would differ under another treatment program. The stopping-rule statement adds important context, but does not replace a comparative analysis.
More generally, a treatment objective is not a result, and a planning calculation is not observed power. The registry's planning assumptions are not evidence that an effect was observed. The single-group design, early halt, absence of collected primary outcome data, and lack of reported analyses mean that conclusions about EFS are not supported by this record. The record is informative about the study's intended question, treatment framework, stopping context, and reported safety events, but it does not provide a statistical answer to the primary efficacy question.
13. Why This Trial Matters Statistically
This record illustrates why a clear research question and an analyzed endpoint are both necessary for statistical interpretation. The study set out to examine EFS against a historical reference, with a stated target change in median EFS. But the primary outcome data were not collected, and no analyses are listed. As a result, the planned contrast remains an objective rather than an estimated treatment effect.
The design also makes the nature of the comparison important. A single-group study does not include a concurrent control arm, so a historical reference cannot provide the same direct basis for comparison as a randomized control. General statistical methods can describe uncertainty around an observed estimate, but they cannot remove all uncertainty caused by differences between studies or create an outcome estimate when the endpoint was not collected.
Early termination under a treatment-related toxicity stopping rule further shapes interpretation. It explains why enrollment halted according to the registry, and the adverse-event record gives descriptive safety information. However, early stopping does not itself answer the EFS question. It can also mean that the study does not reach its planned outcome assessment, as reflected in the record's statement that the primary outcome was not collected.
For biostatistical reading, the distinction among a planned target, a safety summary, and an analyzed primary endpoint is essential. The stated target values should not be mistaken for results; the safety percentages should not be treated as comparative effects; and sample-size planning illustrations should not be described as observed power. This record therefore matters as an example of how design, outcome availability, and analysis reporting determine what can—and cannot—be inferred from a clinical trial registry.
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 most direct limitation is that the primary EFS data were not collected. The registry therefore reports no EFS estimate, endpoint-specific uncertainty, or analysis. Although the planned timeframe was 8 years, the record does not establish that participants were followed for that duration.
The study was single-group, with no concurrent control. Its planned reference to Total Therapy II is historical, and the registry does not report methods to address differences between the studies. The available record also does not report a complete EFS event definition, censoring rules, or details of outcome ascertainment. These omissions prevent a detailed assessment of how the intended endpoint comparison would have been made.
Enrollment halted prematurely under a stopping rule involving treatment-related deaths. The registry lists 19 enrolled participants, describes a rule based on the first 20 participants, and lists 3 deaths. The record does not provide a detailed account of the monitoring process, timing, or decision procedures. The treatment description also lacks a complete regimen schedule in the available registry record, so the full treatment exposure cannot be reconstructed from this information.
The safety summaries are descriptive and lack a concurrent comparator. The record does not report event-level counts for each listed term, observation windows, or further details about attribution and duration. It also does not report missing-data methods, multiplicity procedures, an analysis population, or the trial's own sample-size justification. These limitations mean that neither a comparative safety effect nor the planned EFS effect can be estimated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment — NCT01548573.
- Registry record last updated 2017-06-14; status last verified 2017-05.
- Results first posted 2017-06-14.
- 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.
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18. Record Summary
NCT01548573 is a phase 2, single-group study of tandem autologous transplantation for multiple myeloma in participants with less than 12 months of preceding therapy. The registry lists 19 participants, a status of terminated, and primary completion in 2013-07. The stated EFS objective was to compare median EFS with Total Therapy II, with a target change from 4.8 years to 7.2 years.
The registry states that enrollment halted because the study met a stopping rule involving treatment-related deaths and that primary outcome data were not collected. No analyses are listed. The adverse-event record reports 13 participants with serious adverse events, 19 with other adverse events, and 3 deaths, with selected serious-event terms and percentages. These are descriptive summaries from a single-group study, not comparative estimates. The registry record does not provide an analyzed EFS result.