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 Aflibercept for Relapsed Multiple Myeloma (NCT00437034), a na phase 2 study. The primary outcome is Overall Response Rate (Complete [CR] and Partial Response [PR]).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00437034 |
| Phase | Phase 2 |
| Condition | Stage II Multiple Myeloma, Stage III Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with stage II or stage III multiple myeloma that had relapsed or had not responded to previous treatment. The record does not report further eligibility details or describe the characteristics of the participants who enrolled.
Intervention
Participants received aflibercept, described as antiangiogenesis therapy. The planned regimen was an intravenous infusion over 1 hour on day 1, repeated every 2 weeks for up to 6 courses unless disease progression or unacceptable toxicity led to stopping treatment.
Comparator
There was no comparator group. The study is recorded as single-group, with allocation marked NA and masking listed as none. Its results therefore cannot provide a randomized comparison between aflibercept and another treatment or a control condition.
Primary question
The primary endpoint was the number of participants with a complete response or partial response. The registry record describes the response criteria and intended assessment schedule, but does not report the number who achieved either response category. It therefore does not give a posted estimate of the primary outcome.
The study’s stated rationale was to examine side effects and how well aflibercept works in patients whose multiple myeloma had relapsed or was refractory to prior treatment. The registry summary describes possible mechanisms involving delivery of cancer-killing substances to myeloma cells and blocking blood flow to the cancer. These are rationales in the study description, not findings established by the posted results.
The record also lists progression-free survival, overall survival, toxicities, and several biological measures as secondary outcomes. Their inclusion indicates the range of clinical and laboratory outcomes the study intended to examine. The record does not provide results for those outcomes, so they cannot clarify the primary response finding or provide additional estimates of benefit or risk.
With a single group and enrollment of 6, the study can describe only the experience recorded for those participants. Without a comparator, changes during the study cannot be separated from other possible explanations by a randomized contrast. The record also does not report the response count, the number evaluated for response, or how incomplete assessments were handled. The clinical question is therefore visible in the design, but its primary result cannot be evaluated from the registry results described.
3. Trial Design
This was a phase II, single-group study sponsored by the National Cancer Institute (NCI). The registry lists enrollment of 6 and a terminated status. The study start is recorded as 2007-01 and primary completion as 2010-10. The reason for termination is not reported in the registry record.
The design has no parallel control arm: allocation is listed as NA, and masking as none. All participants were assigned to the treatment group described as antiangiogenesis therapy. This structure is suited to recording outcomes among people receiving the study treatment, but it does not support a randomized estimate of how outcomes would have differed under another treatment or no study treatment.
The intervention was aflibercept, administered intravenously over 1 hour on day 1. The intended schedule repeated treatment every 2 weeks for up to 6 courses, with treatment stopping in the event of disease progression or unacceptable toxicity. The registry record gives this planned regimen but does not report how many courses participants actually received, whether the planned schedule was followed, or the reasons individual participants stopped treatment.
The primary endpoint was overall response, defined as the number of participants with complete response or partial response. Response was intended to be assessed at baseline and every 4 weeks during study treatment, until discontinuation due to disease progression, unacceptable toxicities, or patient withdrawal. The registry description cites response criteria from EBMT, IBMTR, and ABMTR. It defines complete response using absence of monoclonal protein by immunofixation for a minimum of 6 weeks, and partial response using a sustained decrease in production of monoclonal serum protein to 50% or less of the pretreatment value.
Secondary outcomes include progression-free survival, overall survival, toxicities, tissue expression patterns of VEGFR subtypes, the apoptotic state of tumor neovasculature, proangiogenic factors such as VEGF, and circulating endothelial progenitors. The record does not report findings for these outcomes. It also does not report a detailed statistical analysis plan, a sample-size justification, or the reason the study was terminated. Those omissions limit interpretation of both the planned design and the available results.
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 | Treatment (Antiangiogenesis Therapy) |
|---|---|
| STARTED | 6 |
| COMPLETED | 0 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Treatment (Antiangiogenesis Therapy) |
|---|---|
| Adverse Event | 1 |
| Disease progression during treatment | 5 |
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 | Treatment (Antiangiogenesis Therapy) |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 59 (37 to 68) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 5 |
| Race/Ethnicity, Customized: White | participants | 4 |
| Race/Ethnicity, Customized: African American | participants | 1 |
| Race/Ethnicity, Customized: Unknown | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (Complete [CR] and Partial Response [PR]), measured over At baseline and every 4 weeks during study treatment until treatment discontinuation due to disease progression, unacceptable toxicities and/or patient withdrawal..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with an overall response, combining complete response and partial response. It is a count-based endpoint: participants are classified according to whether their disease met the response criteria, and the endpoint records how many met either of the two specified response categories. The registry record does not give that count or the number of participants included in the response assessment.
Response endpoints are used in clinical studies to describe whether disease measures meet predefined criteria for improvement during treatment. Here, the registry cites criteria that distinguish complete response, partial response, stable disease, and progression, with a separate description of symptomatic deterioration. The stated primary endpoint combines only complete and partial response; it does not combine stable disease or progression with response.
The intended assessment schedule was baseline and every 4 weeks during study treatment, continuing until treatment discontinuation for disease progression, unacceptable toxicities, or patient withdrawal. Repeated assessment can identify response status over the treatment period, but a participant-level response summary also depends on how assessments are interpreted and how missing or incomplete evaluations are handled. Those details are not reported in the registry record.
The record states that a 95% confidence interval was intended to be estimated using binomial proportions, but was not computed due to small sample size. A confidence interval would express the uncertainty around an estimated response proportion; without the response count and denominator, neither that estimate nor its precision can be assessed from the posted results. The endpoint definition is reported, but the primary outcome result itself is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record identifies a primary response endpoint but does not post its result. It does not give the number of participants with complete or partial response, or the number assessed for response. Consequently, no response proportion or interval can be reported from this record. This is not evidence that no participants responded; the result is simply not reported in the registry record.
Enrollment was 6, and the study was single-group. Even if a response count were available, it would describe the outcomes observed among this small group and would be statistically uncertain. The registry explicitly says that the planned 95% confidence interval based on binomial proportions was not computed due to small sample size. The lack of an interval leaves the precision of any primary response estimate unavailable as well as its value.
The absence of a comparator also matters. An outcome observed among people receiving aflibercept cannot by itself show what would have happened to comparable participants under another treatment or without the study treatment. A single-group result is descriptive, not a randomized estimate of a treatment contrast. No causal conclusion about the effect of aflibercept follows from the design or the posted counts.
The status is terminated. The registry record does not state why the study was terminated, whether termination affected recruitment or follow-up, or whether the planned assessments were completed. The primary completion date is recorded as 2010-10, but that date does not establish the completeness of every outcome assessment. The number enrolled is not necessarily the number with evaluable response data, and the record does not state the analysis population.
The safety information is also limited. For the treatment group, 0 of 6 participants at risk are recorded as having a serious adverse event, while 6 of 6 are recorded as having other adverse events. No serious adverse event terms are listed, and deaths are not reported. These counts describe the registry entries; they do not establish whether events were caused by treatment, how severe non-serious events were, how long participants were followed, or whether all relevant events were captured.
Secondary outcomes include survival, toxicities, and laboratory or tissue measures, but results for them are not reported in the registry record. No analyses are listed. In combination, these omissions mean that the record offers a description of the question, planned regimen, endpoint definitions, and limited safety counts, but not enough results to estimate antitumor activity or fully characterize safety. The appropriate interpretation is therefore about what was recorded and what remains unknown, rather than a conclusion about treatment performance.
9. Statistical Methods Explained
The registry identifies overall response as a count of participants with complete or partial response. A count endpoint is constructed by applying the response definitions to each participant’s assessments and counting those who meet the specified categories. To turn that count into a response proportion, an analysis also needs a denominator: the number of participants included in the response evaluation. The record reports enrollment of 6 but does not report the response count, the evaluated denominator, or the resulting proportion. Enrollment alone should not be assumed to equal the number analyzed.
The response definitions distinguish several clinical states. Complete response requires complete absence of monoclonal protein by immunofixation for a minimum of 6 weeks. Near complete response is separately defined in the registry, but it is not part of the stated primary endpoint, which combines complete and partial response. Partial response requires a sustained decrease in production of monoclonal serum protein to 50% or less of pretreatment value. Stable disease means no significant change from baseline. Progression includes a rise in production rate meeting the stated criterion or changes in lesions or marrow plasmacytosis. Symptomatic deterioration is also described. Clear distinctions matter because a participant’s classification depends on the endpoint’s prespecified categories, not simply on whether a clinician considered the disease better or worse.
The endpoint was to be assessed at baseline and every 4 weeks during study treatment until discontinuation because of disease progression, unacceptable toxicities, or patient withdrawal. Repeated assessments can capture response over time, but a final summary requires a rule for combining assessments. For example, an analysis plan may specify whether a response must be confirmed, which assessment period determines the best response, and how a participant without a later assessment is classified. These rules are not reported in the registry record and should not be inferred from the outcome definition alone.
The registry says a 95% confidence interval for the binomial response estimate was intended but was not computed due to small sample size. In general, a binomial proportion represents the share of evaluated participants meeting a binary outcome, such as response versus no response. A confidence interval gives a range of values compatible with the observed estimate under the method’s assumptions, expressing statistical uncertainty rather than a guarantee that the true value falls within that particular interval. Small samples tend to make estimates less precise, and an interval may be wide. In this record, the response estimate and interval are both unavailable, so their numerical precision cannot be assessed.
The interval method is described only as based on binomial proportions. The record does not specify a particular interval formula or report a calculated interval. It would therefore be inappropriate to reconstruct one: the response count and analysis denominator are missing, and the registry explicitly says the intended interval was not computed. General descriptions of binomial methods explain the type of analysis, but do not substitute for the missing trial result.
The design is single-group, with no randomized comparator and no masking. In general, a single-arm study can describe outcomes during treatment, but it cannot use random allocation to balance both measured and unmeasured differences between treatment groups. A comparison with an external expectation would require additional assumptions and information that are not reported in the registry record. No controlled treatment effect or comparative significance test can be inferred from this design.
Enrollment of 6 is the only sample count reported for the study overall. A statistical analysis plan, a formal sample-size justification, and any interim analysis plan are not reported in the registry record. The record’s statement that a confidence interval was not computed due to small sample size explains the absence of that interval, but it does not establish why the study enrolled 6 or whether that enrollment matched a planned target. The reason for termination is also not reported.
General statistical interpretation should separate the observed count, the uncertainty around a count-based estimate, and the design’s ability to support comparisons. A small study may produce a count that is useful for describing what was recorded, while remaining too imprecise to support broad claims. Here, the primary count is not reported at all, so even a descriptive response estimate is unavailable. The safety counts offer limited descriptive information, but lack event details and follow-up context.
The registry lists no analysis entries. It does not describe the statistical methods for the secondary outcomes, the analysis populations, or how the investigators handled missing observations. For time-to-event outcomes such as progression-free survival and overall survival, general methods often account for differing follow-up and censoring, but the record does not specify whether such methods were used or provide the underlying results. Statistical concepts can clarify what information would be needed; they cannot fill in unreported trial analyses.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary response endpoint and several secondary outcomes, including progression-free survival, overall survival, toxicities, and biological measures. It does not report a strategy for controlling multiplicity, such as how interpretation would account for examining multiple outcomes. It also does not report a hierarchy among the secondary outcomes or specify which would be treated as confirmatory versus exploratory. Without such information, results across multiple endpoints would need cautious interpretation even if they were available.
No analysis entries are listed, and the record does not provide a detailed statistical analysis plan. It does not state which participants would be included in each analysis, whether analyses would use all enrolled participants or only those with evaluable assessments, or how participants who stopped treatment early would be handled. The enrolled group and the endpoint-specific analysis population should not be assumed to be identical.
Missing-data rules are not reported in the registry record. The primary endpoint requires response assessments over time, but the record does not say how absent, incomplete, or unevaluable assessments would affect a participant’s response classification. It also does not report the amount or pattern of missing outcome data. Without those details, the possible effect of missing assessments on the response summary cannot be evaluated.
The stated response assessment schedule and the reasons for discontinuation identify circumstances in which follow-up could end, but they do not establish how the analysis treated those circumstances. The record gives no reported interim analysis plan or stopping rule. It also does not say whether the termination was related to a planned statistical decision. These matters are not reported in the registry record and should not be inferred from the terminated status.
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 |
|---|---|---|---|
| Treatment (Antiangiogenesis Therapy) | 0 | 6 | 0.0% |
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 |
|---|---|
| Treatment (Antiangiogenesis Therapy) | 6 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Antiangiogenesis Therapy) |
|---|---|---|
| Hypertension | Vascular disorders | 6 of 6 |
| Anemia | Blood and lymphatic system disorders | 4 of 6 |
| Fatigue | General disorders | 3 of 6 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Voice changes | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Neutrophil count decreased | Investigations | 2 of 6 |
| Headache | Nervous system disorders | 2 of 6 |
| Insomnia | Psychiatric disorders | 1 of 6 |
| Dizziness | Nervous system disorders | 1 of 6 |
| ODYNOPHAGIA (PAINFUL SWALLOWING) | Gastrointestinal disorders | 1 of 6 |
The registry’s treatment-group safety counts list 6 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 6 at risk and 6 affected. These are counts of participants, not counts of individual events, so a participant may have experienced more than one event. The record does not provide event-level detail for the other adverse events.
No serious adverse event terms are listed. The deaths field has no reported value, so deaths are not reported in the registry record; a blank entry should not be read as a count of zero. The posted counts also do not describe event timing, duration, severity within the other-adverse-event category, or how long participants were monitored.
These safety entries are descriptive and do not establish causation. The record does not say whether an event was judged related to aflibercept, nor does it provide a comparator group for estimating relative risk. With enrollment of 6, the counts represent a small group and cannot characterize uncommon events reliably. They also do not establish that no additional events occurred beyond those captured in the registry entry.
In general, safety counts are most interpretable when the definitions, follow-up period, event terms, and analysis population are clear. Several of those details are not reported in the registry record. The figures should therefore be read narrowly as the posted participant counts for the treatment group, rather than as a complete safety profile.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II, single-group study of aflibercept was conducted in people with stage II or stage III relapsed or refractory multiple myeloma, with enrollment of 6 and terminated status. It describes a planned treatment schedule, the primary response endpoint, response criteria, secondary outcomes, and a small set of safety counts. These registry entries characterize the study and its registry entries, but do not supply a primary response result.
The record does not report how many participants achieved complete or partial response, how many were assessed, or a response proportion. It states that a 95% confidence interval was intended but not computed due to small sample size. As a result, the posted information cannot establish the size or precision of the response estimate. It also cannot show whether participants experienced stable disease, progression, or symptomatic deterioration in the numbers described by the response criteria.
The safety entries show 0 of 6 participants at risk with a recorded serious adverse event and 6 of 6 with a recorded other adverse event. These counts do not say whether events were treatment-related, identify the other event terms, or provide information on event duration and follow-up. The record does not report deaths. Such entries are not sufficient to establish that the treatment is safe or unsafe.
Because the study has no randomized comparator, it cannot estimate a comparative treatment effect. The registry summary includes proposed mechanisms, but those statements are rationale rather than trial findings. The record also does not report results for survival or the other secondary outcomes. Thus, it does not establish whether aflibercept changed disease outcomes, how outcomes compare with another approach, or the balance of benefits and harms.
The appropriate conclusion is limited: the registry documents a small, terminated, single-group study and describes its planned endpoint and available safety counts, while leaving the primary efficacy result and many analysis details unreported. Missing results should not be interpreted as evidence of no response or of no safety events beyond the posted counts. Nor should the study design or rationale be treated as proof of a treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically informative because its registry record illustrates the difference between a defined endpoint and a reported endpoint result. The primary outcome is clearly named and its response categories are described, yet the record does not provide the response count or the denominator used for analysis. Without those values, readers cannot obtain even a descriptive response estimate from the posted results.
The record also explicitly states that a 95% confidence interval was intended but not computed due to small sample size. This highlights why precision matters alongside an estimate: a count or proportion from a small group can be highly uncertain, and a confidence interval would help communicate that uncertainty. In this case, the estimate itself is not reported, so the intended interval cannot be evaluated or reconstructed.
The single-group design makes the distinction between description and comparison especially important. A study can document what happened to participants receiving an intervention, but without a comparator it cannot isolate an effect relative to another treatment. The treatment rationale and planned regimen do not change that limitation. Any inference beyond the participants’ recorded experience would require assumptions or evidence not presented in the registry record.
The safety figures similarly demonstrate the value of context. Counts of participants with serious and other adverse events are useful descriptive entries, but they are not a complete account of event types, timing, attribution, or follow-up. A small enrollment also limits the ability to characterize less common harms. Readers need the counts and their definitions, but should not turn them into broader claims about safety.
Finally, the terminated status and unreported analysis details matter for transparency. The reason for termination, missing-data handling, analysis populations, and multiplicity approach are not reported in the registry record. Recognizing those gaps is part of sound statistical reading: a clearly defined endpoint is not a substitute for a posted result, and a registry status does not explain why a study ended.
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 endpoint result is not reported in the registry record. The number of participants with complete or partial response, the number assessed, and the resulting response estimate are unavailable. Although the record says a 95% confidence interval was intended, it also says that interval was not computed due to small sample size.
Enrollment was 6, which limits the amount of information available from this study. The record does not state how many participants completed treatment or had evaluable response assessments. It does not report treatment exposure, the number of courses received, or reasons for individual treatment discontinuation. The planned schedule therefore cannot be treated as a description of actual exposure.
The design has no comparator group, and masking is listed as none. It cannot provide a randomized contrast or separate treatment-associated outcomes from other explanations. The study is also marked terminated, but the reason for termination is not reported. The registry record does not establish whether termination affected recruitment, assessment, follow-up, or availability of results.
Important analysis details are absent: the statistical analysis plan, sample-size justification, analysis populations, missing-data rules, and approach to multiple outcomes are not reported. The record does not provide results for the listed secondary outcomes, and it lists no analysis entries. This prevents assessment of consistency across outcomes or of the methods used to analyze them.
Safety reporting is limited to participant counts for serious and other adverse events. Serious event terms are not listed, deaths are not reported, and other event terms and event-level details are unavailable. The registry entries do not establish attribution, duration of monitoring, or completeness of event capture. Together, these limitations restrict both efficacy interpretation and safety characterization; they should not be replaced with assumptions about unreported results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Aflibercept for Relapsed Multiple Myeloma — NCT00437034.
- Registry record last updated 2021-02-08; status last verified 2021-01.
- Results first posted 2015-07-29.
- 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
NCT00437034 is a phase II, single-group study titled “Aflibercept for Relapsed Multiple Myeloma,” sponsored by the National Cancer Institute (NCI). The registry lists enrollment of 6, no masking, and terminated status. The study start is recorded as 2007-01 and primary completion as 2010-10.
The intervention was intravenous aflibercept, planned over 1 hour on day 1 and repeated every 2 weeks for up to 6 courses unless disease progression or unacceptable toxicity occurred. The primary endpoint was the number of participants with complete or partial response, assessed at baseline and every 4 weeks during study treatment.
The registry describes response criteria but does not report the primary response count or estimate. It says a 95% confidence interval was intended but was not computed due to small sample size. Safety entries list 0 of 6 participants at risk with a serious adverse event and 6 of 6 with other adverse events. No serious event terms are listed, and deaths are not reported. Results for the secondary outcomes, the reason for termination, and key analysis details are not reported in the registry record.