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 Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma (NCT00724568), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00724568 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 74 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with newly diagnosed multiple myeloma. The registry record reports 74 enrolled across the phase I/II study, including 42 in phase I.
Intervention
Combination therapy with lenalidomide, bortezomib, dexamethasone, and Doxil. The registry describes four dose levels, with dose changes involving lenalidomide and Doxil.
Comparator
There is no separate control group in this single-group study. Allocation is recorded as not applicable, so the design does not provide a randomized comparison with another treatment or with no treatment.
Primary question
What maximum tolerated dose was reported for the combination? The registry names maximum tolerated dose as the primary outcome, with a timeframe of 1 month post treatment, but the result is not reported in the registry record.
The study also identifies the percentage of patients achieving partial or complete response as a secondary outcome. That outcome could describe tumor response in the enrolled group, but its result is not reported in the registry record. Without a comparator, any response observed would be a description of outcomes among participants receiving the combination, not a randomized estimate of how the combination compares with another approach.
The central statistical question is therefore narrower than a treatment-versus-control question: whether the registry reports a dose-finding outcome and how clearly it reports the associated results. It names the maximum tolerated dose as the primary endpoint and gives details of four planned dose levels, but it does not provide the endpoint value or an analysis explaining how it was selected. The record also does not report a response estimate. Consequently, the posted information does not quantify the primary outcome or establish a comparative treatment effect.
3. Trial Design
This was a phase I/II, single-group study sponsored by the University of Michigan Rogel Cancer Center. The registry describes a study of lenalidomide, bortezomib, dexamethasone, and Doxil for patients with newly diagnosed multiple myeloma. It records 74 participants enrolled, of whom 42 were in phase I. The study is marked completed, with a start of 2008-05 and primary completion of 2009-04.
The design has no separate comparison arm: allocation is recorded as not applicable, and masking is recorded as none. Thus, participants were not described as being randomized between the combination and a control treatment. This structure is consistent with a dose-finding question, but the specific dose-escalation rules, toxicity criteria, and decision procedure for selecting the maximum tolerated dose are not reported in the registry record. Their absence means the named endpoint can be described, but its derivation cannot be reconstructed from the record.
The regimen description lists four dose levels. Lenalidomide is 15 mg daily on days 1-14 at dose level 1, 20 mg at dose level 2, and 25 mg at dose levels 3 and 4, followed by a 7-day rest in a 21-day cycle. Bortezomib is listed at 1.3 mg/m2 on days 1, 4, 8, and 11, and dexamethasone at 20 mg on specified days. Doxil is listed at 20 mg/m2 on day 4 for dose levels 1-3 and 30 mg/m2 at dose level 4. The broader arm description mentions 4-8 cycles. The registry record does not report how many participants received each dose level or the resulting dose-limiting toxicity findings.
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 | Phase I | Phase II |
|---|---|---|
| STARTED | 42 | 32 |
| COMPLETED | 42 | 32 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: A total of 74 patients were enrolled in this phase 1/2 study: 42 in phase 1.
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.
Population: A total of 74 patients were enrolled in this phase 1/2 study. 2 patients were not evaluable for the Dose Limiting Toxicity (DLT) and therefore only 72 are included in the baseline analysis population.
| Characteristic | Unit | Combination Drug Therapy |
|---|---|---|
| Participants analysed | 72 | |
| Age, Continuous | years | 59 (29 to 77) |
| Sex: Female, Male: Female | Participants | 31 |
| Sex: Female, Male: Male | Participants | 41 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD), measured over 1 month post treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled maximum tolerated dose (MTD) of the combination therapy. It is recorded as a number, with mg as the unit and a timeframe of 1 month post treatment. The accompanying description lays out four dose levels, varying the daily lenalidomide dose across the first three levels and increasing the listed Doxil dose at the fourth. The registry does not state the observed MTD value, the number of participants contributing to that result, or the rules used to identify it.
In general, an MTD is used in early-phase research to summarize a dose-finding decision based on tolerability. It is not itself a measure of comparative benefit. Its interpretation depends on how toxicity is defined, how long participants are observed, and how the dose-selection rule handles toxicity at each level. Those protocol details are not reported in the registry record, so the endpoint label alone cannot establish what operational definition was applied.
The listed secondary outcome is the percentage of patients achieving partial or complete response. That outcome would describe response frequency, but no response result is reported in the registry record. Neither endpoint can be evaluated quantitatively from the posted result information because no outcome values or statistical estimates are listed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the study’s broad design and enrollment: a phase I/II, single-group investigation with 74 enrolled participants, including 42 in phase I. It identifies maximum tolerated dose as the primary outcome and provides a regimen description spanning four dose levels. However, it does not report the primary endpoint value. It also does not report the percentage achieving partial or complete response, despite listing that as a secondary outcome. The available record therefore does not show which dose was selected or how often response occurred.
No inferential analyses are listed in the registry record. There is no reported estimate with a confidence interval, no p-value, and no statistical comparison. A confidence interval, in general, describes the range of values compatible with an estimate under a specified statistical procedure; without an estimate and interval, the precision of an outcome cannot be assessed. The absence of these statistics is distinct from evidence that an outcome was absent: the registry record does not provide the corresponding result.
The single-group design also sets a limit on interpretation. Any outcome measured among participants receiving the combination would be descriptive of that group. It would not, by itself, estimate what would have happened to comparable participants receiving another regimen or no study treatment. There is no randomized control group against which to separate the treatment experience from other influences on observed outcomes.
The safety data report 3 participants affected by serious adverse events and 24 affected by other adverse events, among 74 at risk in each category. Four serious-event terms are listed, each with a reported value of 1.4%. These are registry safety summaries, not an estimate of comparative risk; the study has no control group. The registry record does not report a death count. The listed adverse-event information should therefore be read as a description of recorded events in this study, not as a basis for comparing safety with another treatment.
Overall, the posted record supports a description of the study’s purpose, regimen, enrollment, and selected safety summaries. It does not support a numerical conclusion about the primary dose-finding result, response frequency, or comparative benefit. The missing endpoint results and analysis details prevent assessment of the uncertainty around those outcomes.
9. Statistical Methods Explained
Statistical interpretation begins with the question the design can answer. This study is listed as single-group, with allocation not applicable and masking none. It has no randomized control arm. Its named primary question is dose finding, not a treatment comparison. The outcome is recorded as a number in mg, but the registry record does not report the value or the method used to select it.
What does a dose-finding outcome represent?
In general, early-phase dose-finding studies use observed tolerability across dose levels to guide a dose-selection decision. The meaning of a maximum tolerated dose depends on the protocol’s definition of a dose-limiting toxicity, the observation window, the number of participants treated at each level, and the rule for escalating, holding, or reducing doses. These details are not reported in the registry record. The endpoint name and dose schedule do not reveal whether the decision followed a fixed rule, a model, or another process.
The registry lists four dose levels. The lenalidomide schedule rises from 15 mg to 20 mg and then 25 mg daily on days 1-14, with a 7-day rest in 21-day cycles. The dose listed for Doxil is 20 mg/m2 at levels 1-3 and 30 mg/m2 at level 4. Bortezomib is listed at 1.3 mg/m2 on days 1, 4, 8, and 11; dexamethasone is listed at 20 mg on specified days. These regimen details identify planned dose levels, but they do not supply participant-level exposure, observed toxicities by level, or the resulting dose-selection calculation.
How should an estimate and its precision be read?
In general, a point estimate gives a single summary of an outcome, while a confidence interval communicates uncertainty around that summary under the method used. For a response percentage, an interval would help show how imprecisely the observed proportion is estimated, particularly when the number of participants is limited. For a dose-finding result, uncertainty and the decision rule would need to be interpreted in the context of the design. No primary result, response estimate, confidence interval, or p-value is reported in the registry record, so the precision of these outcomes cannot be assessed.
For count outcomes, variability can exceed what a simple Poisson model predicts when events are more dispersed than that model allows. In general, over-dispersion matters because a model that understates variability can produce intervals that are too narrow and tests that are too optimistic. The registry record does not identify a count model or provide event-level analysis for the primary endpoint. No conclusion about model choice or over-dispersion can be drawn from the posted results.
What can planning calculations establish?
In general, a sample-size calculation depends on the design, outcome type, target effect, significance level, allocation, and assumptions about variability. A planning illustration based on equal allocation between two arms and a normal approximation describes a hypothetical comparison framework. It is not the design recorded for this single-group study. Such an illustration is not observed power and cannot replace a dose-finding plan. The registry record does not report the trial’s own sample-size justification, dose-escalation design, or assumptions used to plan enrollment.
The registry lists 74 enrolled and 42 in phase I, but does not report the number evaluable for each endpoint or the number treated at each dose level. Enrollment alone is not enough to infer endpoint denominators. The outcome-specific analysis population, handling of participants who discontinued or had missing measurements, and any sensitivity analyses are not reported in the registry record.
Finally, no statistical analysis is listed. The record does not state whether outcome summaries were adjusted, whether multiple dose levels or outcomes were tested formally, or whether any interim analyses were performed. These are not details that can be inferred from the study title, phase, or regimen. Without the outcome values and analysis methods, the results cannot be independently reconstructed or their statistical uncertainty quantified.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: maximum tolerated dose as the primary outcome and the percentage achieving partial or complete response as a secondary outcome. It does not report outcome results or analyses for either measure. The registry record also does not report a multiplicity strategy, such as a prespecified hierarchy, an adjustment for multiple testing, or a distinction between confirmatory and exploratory analyses beyond the primary and secondary labels.
In general, multiplicity arises when several outcomes, comparisons, time points, or dose levels are examined. The more questions addressed formally, the greater the opportunity for a chance finding if each is tested without an appropriate strategy. That general concern does not establish that this study conducted multiple statistical tests; no analyses are listed in the registry record. The number and type of tests, if any, are not reported.
Missing-data methods and analysis populations are also not reported in the registry record. Although 74 participants were enrolled and 42 were in phase I, the record does not give endpoint-specific denominators, clarify who was considered evaluable, or describe how incomplete observations were handled. It does not report whether participants were analyzed according to enrollment, treatment received, or another population definition.
These omissions limit interpretation of both the primary and secondary outcomes. For a dose-finding endpoint, the number treated and observed at each dose level is essential context. For a response percentage, the denominator and missing-response handling affect what the percentage represents. Without these details, readers cannot assess whether the reported enrollment corresponds to the analyzed population or how robust an outcome would be to missing observations.
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 |
|---|---|---|---|
| Combination Drug Therapy | 3 | 74 | 4.1% |
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 |
|---|---|
| Combination Drug Therapy | 24 of 74 |
Most frequent serious adverse event terms
| Event term | Organ system | Combination Drug Therapy |
|---|---|---|
| Lung Hemorrhage | Respiratory, thoracic and mediastinal disorders | 1 of 74 |
| Pneumonia with Grade 3 or 4 Neutropenia | Infections and infestations | 1 of 74 |
| Pneumonia with Normal Absolute Neutrophil Count | Infections and infestations | 1 of 74 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 1 of 74 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Combination Drug Therapy |
|---|---|---|
| Fatigue (asthenia, lethargy, malaise) | General disorders | 17 of 74 |
| Anemia | Blood and lymphatic system disorders | 10 of 74 |
| Constipation | Gastrointestinal disorders | 10 of 74 |
| Nausea | Gastrointestinal disorders | 10 of 74 |
| Dizziness | Nervous system disorders | 7 of 74 |
| Neuropathy: sensory | Nervous system disorders | 7 of 74 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 74 |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | 6 of 74 |
| Platelets | Blood and lymphatic system disorders | 6 of 74 |
| Diarrhea | Gastrointestinal disorders | 6 of 74 |
Serious events with the highest arm-level rate: lung hemorrhage (1.4%), pneumonia with grade 3 or 4 neutropenia (1.4%), pneumonia with normal absolute neutrophil count (1.4%), pneumonitis (1.4%).
The safety summary lists 74 participants at risk for serious adverse events and 74 at risk for other adverse events. It reports 3 affected by serious adverse events and 24 affected by other adverse events. The registry record lists Lung Hemorrhage, Pneumonia with Grade 3 or 4 Neutropenia, Pneumonia with Normal Absolute Neutrophil Count, and Pneumonitis as serious-event terms, each with a reported value of 1.4%.
These entries describe safety reporting in the combination group. They are not a comparison with another treatment, because the study has no separate control group. The registry record does not clarify whether the event terms represent distinct participants or whether a participant could contribute to more than one term, so the listed terms should not be added together to infer a number of affected people. A death count is not reported in the registry record.
In general, an adverse-event count does not by itself establish that the study treatment caused each event. These figures should be read as recorded events during the study, not as causal estimates or comparative safety measures. The registry record does not provide further detail about event timing, severity beyond the terms shown, exposure duration, or how events were attributed.
12. What the Result Does, and Does Not, Mean
The registry record describes an early-phase investigation of a four-drug regimen in newly diagnosed multiple myeloma, with maximum tolerated dose named as the primary outcome. It gives enrollment and a planned sequence of dose levels, as well as selected safety summaries. Those details clarify what was studied and the broad purpose of the study.
They do not establish the value of the maximum tolerated dose. The primary result is not reported in the registry record, and no dose-level toxicity findings or selection procedure are given. The record also lists response as a secondary outcome but does not report a response result. Without endpoint values, readers cannot judge the magnitude or precision of the stated outcomes.
The single-group design is important. It can describe outcomes among participants treated with the combination, but does not provide a randomized comparison with another regimen. Even if response or toxicity results were available, a group-level observation in this design would not by itself show how outcomes compare with a control group. The posted safety counts likewise cannot quantify excess risk relative to another treatment.
In general, a study’s phase and endpoint indicate the type of question it is designed to address, but do not substitute for the results or analysis plan. A dose-finding endpoint is distinct from a test of comparative efficacy. A reported count or percentage also needs an appropriate denominator, definitions, and uncertainty measure to support a precise interpretation. Those details are not reported for the efficacy outcomes in this record.
The defensible conclusion is therefore about documentation, not treatment effect: the registry record describes a completed phase I/II single-group study and reports some enrollment and safety information, but does not report the primary endpoint value, response result, or statistical analysis. No conclusion about comparative benefit or the precision of efficacy outcomes follows from these posted results.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting need to be read together. A phase I/II label and a detailed dose schedule identify a dose-finding context, while the single-group structure indicates that the study is not a randomized treatment comparison. These features shape the questions the data could address, regardless of how promising or familiar a regimen might seem.
The maximum tolerated dose is named as the primary outcome, but a dose-finding result cannot be interpreted from the list of dose levels alone. It requires the observed toxicity information, the number treated at each level, the observation period, and the rule used to select a dose. Those results and methods are not reported in the registry record. This makes the distinction between a planned regimen and an observed endpoint especially important.
The record also highlights that enrollment is not the same as an endpoint denominator. It reports 74 enrolled and identifies 42 in phase I, but does not specify how many contributed to each endpoint or how missing observations were treated. Without that information, even a reported outcome would need careful interpretation.
Finally, the posted safety figures can be described without turning them into a comparative risk estimate. A single-group record gives a description of events among participants, not a controlled contrast. Statistically, the most useful reading is to separate what the registry directly reports from what would require unreported endpoint results, analysis methods, or a comparator. That distinction prevents a dose-finding study from being read as stronger evidence than its design and record support.
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 principal limitation for statistical interpretation is that the primary endpoint result is not reported in the registry record. The record names maximum tolerated dose and gives a timeframe, but no value in mg, dose-level toxicity summary, or selection rule is reported. The secondary response outcome is also listed without a result. Consequently, the effectiveness outcomes cannot be quantified from the posted information.
The registry describes a single-group study with no randomized comparator. This precludes a direct comparative estimate within the study. The design can describe outcomes in the treated group, but cannot isolate a treatment contrast against another group. No analysis results, confidence intervals, p-values, or adjusted estimates are listed.
Additional dose-finding details are missing: the number of participants treated at each dose level, toxicity definitions, dose-limiting observation window, escalation or stopping rules, and the basis for selecting the maximum tolerated dose. The treatment schedule is described, but the broader arm description ends before completing its explanation of the dose-finding objective. The registry record does not report how many participants received each cycle count or dose level.
Endpoint denominators, analysis populations, missing-data methods, and multiplicity procedures are not reported. The summary also does not give a death count or explain whether serious-event terms can overlap across participants. These gaps limit reconstruction and interpretation of the posted safety summaries. They do not establish that a particular method was or was not used; they mean the method is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma — NCT00724568.
- Registry record last updated 2017-06-02; status last verified 2017-05.
- Results first posted 2014-09-10.
- 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
NCT00724568 is a completed phase I/II, single-group study sponsored by the University of Michigan Rogel Cancer Center. It enrolled 74 participants with newly diagnosed multiple myeloma, including 42 in phase I. The regimen combines lenalidomide, bortezomib, dexamethasone, and Doxil, with four described dose levels.
Maximum tolerated dose is the primary outcome, with a timeframe of 1 month post treatment. Percentage achieving partial or complete response is listed as a secondary outcome. Neither outcome result is reported in the registry record, and no statistical analyses are listed. Safety summaries report 3 affected by serious adverse events and 24 by other adverse events among 74 at risk in each category. The record has no randomized comparison group, so its posted safety summaries are descriptive rather than comparative.