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 Phase 1-2 Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma (NCT01355705), a na phase 1, phase 2 study. The primary outcome is Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01355705 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Michaela Liedtke |
| Results posted | Yes |
2. Clinical Question
Population
People with relapsed or refractory multiple myeloma who required additional treatment. The registry record lists multiple myeloma as the condition and records enrollment of 14 participants.
Intervention
The study regimen combined amrubicin, lenalidomide, and weekly dexamethasone. Amrubicin was described as an intravenous treatment on Day 1 of each 3-week cycle, beginning at 40 mg/m2 and continuing for a maximum of 4 cycles. Lenalidomide and dexamethasone were also described in the treatment schedule.
Comparator
No separate comparator group is recorded. The study is listed as a single-group study with no masking and no allocation. Its observations therefore describe the treated group; they do not provide a direct randomized comparison with another treatment or with no treatment.
Primary question
The primary outcome asks about response rates at 12 weeks after treatment with amrubicin, lenalidomide, and dexamethasone, using modified International Myeloma Working Group Uniform Response Criteria. The registry record does not report the response-rate results, so the outcome cannot be interpreted as an observed estimate from the posted record.
3. Trial Design
This completed study is registered as a phase 1-2, single-group study in relapsed or refractory multiple myeloma. The registry record gives enrollment as 14 and lists the study start as 2011-08 and primary completion as 2016-07. Allocation is recorded as not applicable, and masking is listed as none. There is no separate control arm in the record, so comparisons with another treatment cannot be made within this study.
The treatment group is described as receiving amrubicin with lenalidomide and dexamethasone. Amrubicin was to be given intravenously on Day 1 of each 3-week cycle, starting at 40 mg/m2, for a maximum of 4 cycles. The description lists lenalidomide at 10 or 15 mg daily by mouth on Days 1 to 14, and dexamethasone at 40 mg weekly by mouth on Days 1, 8, and 15. Aspirin and pegfilgrastim are also listed as interventions, but the arm description does not provide a complete schedule for them; the aspirin entry is unfinished, and a pegfilgrastim schedule is not reported in the registry record.
The primary outcome is a response-rate measure at 12 weeks. Secondary outcomes are duration of response, progression-free survival, and time-to-next treatment. The registry record lists 4 outcome measures, but lists no analyses. A completed study status indicates that the record reports the study as completed; it does not, by itself, establish that all planned outcomes were reported or that the study demonstrated a particular 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 | Amrubicin + Lenalidomide + Dexamethasone |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
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 | Amrubicin + Lenalidomide + Dexamethasone |
|---|---|---|
| Participants analysed | 14 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 |
| Age, Categorical: >=65 years | Participants | 6 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 9 |
| Region of Enrollment: United States | participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria, measured over 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants classified by response after treatment with amrubicin, lenalidomide, and dexamethasone at 12 weeks. Classification is based on modified International Myeloma Working Group Uniform Response Criteria. These criteria distinguish response categories such as complete response, stringent complete response, near complete response, partial response, very good partial response, and minimal response. They also define stable disease and progressive disease using measures of monoclonal protein, marrow plasma cells, bone lesions, and other disease findings.
A response-rate outcome is useful because it describes how many participants meet a specified disease-response classification at a stated assessment time. It can communicate the observed frequency of response in a treatment group, while the classification criteria set common rules for assigning outcomes. Response categories are not interchangeable: some indicate deeper changes than others, while stable disease and progressive disease describe different clinical states. The registry record does not state which categories were combined to form the reported response-rate endpoint, beyond naming response rates and the modified criteria. That detail is not reported in the registry record.
No response counts, percentages, or uncertainty estimates are reported in the registry record. Consequently, the endpoint definition alone does not reveal the rate observed in this study or how precisely it was estimated. The listed secondary time-to-event outcomes address different questions and cannot substitute for the missing primary response-rate result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically defined response-rate endpoint at 12 weeks, but it does not report the observed response rate. Without the number of participants in each response category, an efficacy denominator, or an uncertainty interval, the posted record cannot establish the size or precision of any response estimate. No conclusion about the magnitude of response can be drawn from an endpoint description alone.
The design also limits what can be inferred. This was a single-group study, with no separate comparator recorded. Any response observed in the treated group would be a description of that group under the study conditions, not a direct estimate of how the regimen compares with another treatment. A within-group result cannot by itself separate the influence of treatment from other explanations, such as the course of disease or differences among participants. This is a general limitation of non-comparative treatment studies.
The record gives enrollment as 14, but does not report the primary efficacy analysis population or the denominator used for the response rate. Enrollment and the analysis denominator need not be assumed to be identical. The registry record also does not report whether any participants lacked a 12-week assessment, how such observations were handled, or whether response categories were combined in a prespecified way. Those details matter because the estimate depends on who was evaluated and how unevaluable or missing observations were treated.
Safety information is more specific in the posted record than efficacy information. The treatment group lists 3 participants affected by serious adverse events among 14 at risk, and 12 affected by other adverse events among 14 at risk. Sepsis, cord compression, and progressive disease are each listed among the top serious adverse-event terms at 7.1%. These figures describe reported events in the study group; they do not provide a comparative estimate of risk. The death count is not reported in the registry record.
The record lists duration of response, progression-free survival, and time-to-next treatment as secondary outcomes, but does not provide their results. It also lists no analyses. Thus, neither the response outcome nor the secondary outcomes can be evaluated for effect size, uncertainty, or statistical evidence using this record alone. A lack of posted analysis is not evidence that an effect is absent; it means that the statistical results are not reported in the registry record.
In general, interpretation of a treatment study benefits from estimates accompanied by uncertainty intervals and a clear account of the analysis population. Neither is available for the primary outcome in this record. The most defensible reading is therefore descriptive: the registry documents a completed single-group study, its planned response measure, and selected safety counts, while leaving the principal efficacy result and its precision unreported.
9. Statistical Methods Explained
The registry record identifies the primary outcome as a percentage of participants and lists no analyses. It therefore does not provide an inferential method, an estimated response rate, or an interval quantifying uncertainty. The concepts below explain how such outcomes are generally interpreted; they are not a description of methods confirmed to have been used in this study.
What does a percentage of participants represent?
In general, a binary outcome classifies each participant as meeting or not meeting a defined condition at an assessment. A percentage expresses the number meeting that condition relative to a stated analysis denominator. For a response rate, that denominator and the rule for deciding which response categories count as a response must be clear. The response criteria define disease categories, but the registry record does not report the specific category grouping used for the rate or the denominator used in the analysis.
A percentage is a point estimate: it summarizes the observed data but does not show how much the estimate might vary across comparable samples. A confidence interval is a general statistical tool for representing uncertainty around an estimate under stated assumptions. A narrower interval indicates greater precision under those assumptions, while a wider interval indicates more uncertainty. No confidence interval for the primary response rate is reported in the registry record, so precision cannot be assessed from the posted results.
Why does the single-group design matter?
In general, a single-group estimate answers a descriptive question about the participants observed under the study regimen. A comparative treatment effect requires a contrast between groups or another suitable design and analysis. With no separate comparator recorded, this study cannot provide a randomized between-group comparison. Statistical methods cannot create a control group that the design did not include.
Even a precisely estimated response percentage would not, on its own, show what would have happened to similar participants under a different regimen. That distinction is about the design and the question it can answer, not merely about the choice of statistical test. The record's single-group designation therefore constrains interpretation independently of whether a response estimate is eventually available elsewhere.
What do planning calculations mean?
The planning illustrations associated with the record are described as calculations based on an observed effect, rather than as the trial's original design justification. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe hypothetical planning comparisons; they do not match the recorded single-group design, which has no two-arm allocation.
In general, sample-size planning asks how many participants would be needed under specified assumptions to target a chosen power for detecting an effect. Such a calculation depends on the assumed effect, variability or event rate, analysis method, and design. It is a prospective illustration, not an observed property of the completed study. It must not be read as observed power or as proof that the original study was designed to detect the illustrated effect. The registry record does not report the original sample-size justification or a statistical plan.
Because the primary response result is not reported, the observed effect on which the planning illustrations are based is not available in this record. No planning value or conclusion about the study's adequacy can be independently interpreted from the listed assumptions alone. Furthermore, a two-arm equal-allocation scenario does not describe the actual single-group enrollment structure.
How should uncertainty and sparse outcomes be considered?
In general, binary outcome estimates can be uncertain when there are few observations, especially when the outcome is uncommon or very common. The width and appropriateness of an interval depend on the estimator and assumptions. No particular interval method is named in the registry record, and no response count is reported. It is therefore not possible to assess whether an interval method was suitable or whether the endpoint estimate was stable.
Over-dispersion is a general concern when observed outcomes vary more than a model assumes. In a binary-outcome setting, extra variation can make model-based uncertainty estimates too optimistic if the model does not account for it. Whether over-dispersion is relevant depends on the analysis structure and data. The registry record does not report a model, repeated-measure structure, or diagnostic assessment, so no claim about over-dispersion in this study is supported.
Time-to-event outcomes such as duration of response and progression-free survival are generally analyzed with methods that account for differing follow-up and censoring. Censoring occurs when the event time is not observed for a participant during the available follow-up; such observations are not simply equivalent to observed events. This general explanation does not establish which methods or censoring rules were used for this study. Results and analysis details for these secondary outcomes are not reported in the registry record.
Finally, reporting an estimate, a denominator, a definition, and an uncertainty measure together enables readers to understand what the analysis evaluated. The record identifies an endpoint definition and time frame, but does not report those statistical results for the primary outcome. The interpretation must remain limited to the design and outcome descriptions that are present.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary response-rate outcome and secondary outcomes of duration of response, progression-free survival, and time-to-next treatment. It also lists 4 outcome measures overall. When a study evaluates multiple outcomes or performs multiple comparisons, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity refers to that collection of statistical tests or outcome assessments and to the decisions used to account for them.
No multiplicity strategy, hierarchy of testing, or statistical analysis plan is reported in the registry record. The record also lists no analyses. It is therefore not possible to determine whether outcomes were tested, whether adjustments were planned, or how the primary outcome was distinguished from secondary or exploratory findings. These details should not be inferred from the order in which outcomes are listed.
Missing-data handling is also not reported in the registry record. The primary endpoint has a 12-week assessment time, but the record does not state how many participants contributed an evaluable assessment, whether any assessments were missing, or how missing values were handled. In general, missingness can affect a percentage if the participants without an assessment differ from those with observed outcomes. Different assumptions for missing observations can lead to different estimates, so clear reporting is important.
The analysis population is not reported in the registry record. Enrollment is recorded as 14, and the safety group has 14 at risk, but those entries do not establish the denominator used for the primary efficacy analysis. A statistical report would ordinarily clarify which participants were included and how exclusions or unevaluable outcomes were treated. Without that information and the outcome counts, the primary response percentage cannot be reconstructed or checked.
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 |
|---|---|---|---|
| Amrubicin + Lenalidomide + Dexamethasone | 3 | 14 | 21.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Amrubicin + Lenalidomide + Dexamethasone | 12 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Amrubicin + Lenalidomide + Dexamethasone |
|---|---|---|
| Sepsis | Infections and infestations | 1 of 14 |
| Cord compression | Nervous system disorders | 1 of 14 |
| Progressive disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Amrubicin + Lenalidomide + Dexamethasone |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 12 of 14 |
| Thrombocytopenia | Blood and lymphatic system disorders | 11 of 14 |
| Infection | Infections and infestations | 11 of 14 |
| Neutropenia | Blood and lymphatic system disorders | 9 of 14 |
| Diarrhea | Gastrointestinal disorders | 7 of 14 |
| Fatigue | General disorders | 7 of 14 |
| Hypoalbuminemia | Investigations | 6 of 14 |
| Nausea | Gastrointestinal disorders | 5 of 14 |
| Elevated AST/ALT | Investigations | 5 of 14 |
| Bone pain | Musculoskeletal and connective tissue disorders | 5 of 14 |
Serious events with the highest arm-level rate: sepsis (7.1%), cord compression (7.1%), progressive disease (7.1%).
The safety record lists 3 participants affected by serious adverse events, with 14 at risk in the treatment group. It lists 12 participants affected by other adverse events, also with 14 at risk. These are separate registry summaries; the record does not provide enough detail to determine the full event-level pattern or whether participants experienced more than one event.
The top serious adverse-event terms are sepsis, cord compression, and progressive disease. Each is listed at 7.1%. These percentages are descriptions of the reported serious-event terms, not estimates from a comparison group. The record does not explain whether terms overlap within participants or provide detailed severity, timing, or attribution information. It also does not report a death count.
In general, safety counts should be read in the context of how events were defined, collected, and attributed, along with the size and follow-up of the group at risk. A single-group summary cannot establish how these figures compare with another treatment or with the underlying event frequency in a similar population. The posted safety figures are descriptive, not a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
The record establishes that NCT01355705 was a completed phase 1-2 single-group study of amrubicin with lenalidomide and weekly dexamethasone in relapsed or refractory multiple myeloma. It documents a primary response-rate outcome assessed at 12 weeks under modified International Myeloma Working Group Uniform Response Criteria, as well as secondary outcomes concerning response duration, progression-free survival, and time-to-next treatment.
What the record does not establish is the observed primary response rate. The response counts, percentage, efficacy denominator, and uncertainty estimate are not reported in the registry record. The same is true of results for the listed secondary outcomes. The absence of these results from the record should not be interpreted as a zero response rate or as evidence that no statistical analysis was conducted; the record simply does not report those results or analyses.
The single-group design also means the study does not provide a direct randomized comparison. Even if an outcome estimate were available, it would describe the participants in this group and would not alone show the contrast with another treatment. The registry record does not identify a control group or a comparator outcome.
The safety summary reports serious and other adverse events in the treatment group, including the listed serious-event terms and percentages. Those figures can be read as descriptive safety reporting, but not as evidence of relative risk. The record does not report the death count or enough event-level detail to characterize all aspects of safety.
In general, a treatment result is most informative when the outcome definition, analysis population, estimate, uncertainty, missing-data approach, and design are considered together. In this record, the design and endpoint descriptions are available, but the primary efficacy estimate and key analysis details are not. The supported conclusion is about what was registered and reported, not about whether the regimen did or did not produce a particular response.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting must be considered alongside an endpoint label. A response-rate outcome has an intuitive interpretation as the share of participants meeting a disease-response definition, but the rate cannot be understood without its observed count, denominator, category rule, and uncertainty. The registry record identifies a 12-week assessment and modified response criteria, yet does not report the response result or those supporting statistical details.
The single-group design is also an important statistical feature. It can describe outcomes among people receiving the regimen, but it does not directly estimate a contrast against an alternative treatment. This distinction matters when readers encounter response or safety numbers: observed group outcomes and comparative treatment effects answer different questions. A design's limitations are not resolved simply by applying a more elaborate statistical method.
The record further shows why a sample-size planning illustration should not be mistaken for evidence from the completed study. Planning calculations depend on assumptions and can describe a hypothetical future comparison. The stated illustration uses equal allocation between two arms, while the recorded study is single-group. Those calculations do not establish the original design rationale, observed power, or the precision of an unreported response estimate.
Finally, outcome definitions, missing-data handling, analysis populations, and multiplicity plans all affect interpretation. The registry record lists several outcomes but no analyses, and does not report these methodological details. Clear reporting of these elements would help readers distinguish a missing result from a null result and assess how much confidence to place in any estimate. Here, statistical restraint is essential: the record supports a description of the study design and selected safety data, but not an efficacy conclusion.
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.
Several limitations are specific to the information recorded for this study. The principal limitation is that the primary response-rate result is not reported. The record gives the endpoint criteria and assessment time but no response counts, percentage, efficacy denominator, or uncertainty interval. Without these, the central efficacy outcome cannot be evaluated from the registry record.
The study has a single-group design and no separate comparator recorded. This prevents a direct randomized comparison within the study. The enrollment is recorded as 14, but the registry record does not state the analysis population for the primary endpoint or whether all enrolled participants had an evaluable 12-week assessment.
The record describes modified response criteria, but does not report which response categories were combined for the response-rate calculation. It also does not report missing-data procedures, a statistical analysis plan, multiplicity handling, or analyses. Although secondary outcomes are listed, their results and methods are not reported in the registry record.
The regimen description includes lenalidomide at 10 or 15 mg daily and an amrubicin starting dose of 40 mg/m2, with a maximum of 4 cycles. This records more than one listed lenalidomide dose, but does not explain how dose selection or changes were handled. Aspirin is listed without a complete schedule, and the arm description does not give a pegfilgrastim schedule. These omissions limit the detail available about the regimen as administered.
Safety reporting is also limited: the record gives summary counts and selected serious-event terms, but does not report a death count or enough detail to assess timing, attribution, recurrence, or overlap among terms. These gaps do not show that such information was unavailable to investigators; they mean it is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 1-2 Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma — NCT01355705.
- Registry record last updated 2018-09-18; status last verified 2018-09.
- Results first posted 2017-03-03.
- 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
NCT01355705 is recorded as a completed phase 1-2, single-group study in relapsed or refractory multiple myeloma, with enrollment of 14. The listed regimen combines amrubicin, lenalidomide, and weekly dexamethasone. The primary outcome is a response-rate measure at 12 weeks using modified International Myeloma Working Group Uniform Response Criteria. Duration of response, progression-free survival, and time-to-next treatment are listed as secondary outcomes.
The registry record does not report the primary response-rate result, results for the secondary outcomes, or any analyses. It also does not report the primary analysis denominator, missing-data approach, or multiplicity plan. Safety summaries list 3 participants with serious adverse events and 12 with other adverse events among 14 at risk; sepsis, cord compression, and progressive disease are each listed among the top serious terms at 7.1%. The death count is not reported. The single-group design provides no direct comparator for interpreting efficacy or safety comparatively.