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 A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma (NCT01672736), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01672736 |
| Phase | Phase 1, 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 Health Network, Toronto |
| Results posted | Yes |
2. Clinical Question
Population
Patients with relapsed or relapsed/refractory multiple myeloma. The registry record lists an enrollment of 19 and describes the study as multicenter. It does not provide further eligibility details or report characteristics of the participants who enrolled.
Intervention
ASP7487 (OSI-906) in combination with bortezomib, also named Velcade, and dexamethasone. The registry describes ASP7487 as administered orally at 75, 100 and 150 mg BID continuously for each cycle. Bortezomib and dexamethasone were scheduled alongside it.
Comparator
There was no separate comparator group. The trial is recorded as non-randomized, open-label and single-group, so it does not provide a concurrent control for comparing outcomes under the combination with outcomes under another treatment or no treatment.
Primary question
The designated primary outcome is the maximum tolerated dose of the combination of ASP7487 with Velcade and dexamethasone, measured in milligrams. The description also states that Phase 2 was intended to evaluate antitumor activity at the maximum tolerated dose established in Phase 1. The registry record does not report a result for either objective.
The central clinical research question was whether a tolerable dose of ASP7487 could be identified when it was combined with bortezomib and dexamethasone in people with relapsed or relapsed/refractory multiple myeloma. The Phase 1 component is described as dose escalation. The Phase 2 component is described as an expansion at the maximum tolerated dose, with objective response rate as its stated aim. These are planned aims, not evidence that a dose was established or that a response outcome was observed.
Because this is a single-group trial, its design addresses feasibility and activity within the treated group rather than a comparative treatment effect. There is no randomized allocation or control arm in the registry record. Consequently, the record cannot support a direct comparison of outcomes between the combination and an alternative. The registry status is terminated, but the reason for termination is not reported in the registry record.
3. Trial Design
The registry records a Phase 1/2, multicenter, open-label, non-randomized, single-group study of ASP7487 (OSI-906) with bortezomib and dexamethasone. Enrollment is listed as 19. The trial began in 2012-09, its primary completion date is 2017-03-27, and its status is terminated. The reason it was terminated is not reported in the registry record.
The brief description assigns different aims to the phases. Phase 1 involved dose escalation to determine the maximum tolerated dose of ASP7487 in combination with the recommended dose and schedule of bortezomib and dexamethasone. Phase 2 involved expanding treatment at the maximum tolerated dose established in Phase 1 to evaluate antitumor activity and establish the objective response rate. Although the primary outcome measure is the maximum tolerated dose, the registry record does not include a numerical dose result or a reported objective response rate.
The intervention is recorded as ASP7487, Velcade and dexamethasone. ASP7487 was described as oral dosing at 75, 100 and 150 mg BID continuously for each cycle. Bortezomib was described at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone was administered on bortezomib administration days at 20 mg. These are the recorded regimen details; the registry record does not report how many participants received each ASP7487 dose level or how long participants remained on treatment.
Open-label means the study was not masked, and non-randomized means treatment assignment was not allocated by randomization. With a single group and no control arm, outcome changes cannot be contrasted against a concurrent comparison group. The registry record does not report a more detailed allocation procedure, a sample-size justification, or the statistical plan used to evaluate the study objectives.
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 | ASP7487, Velcade, Dexamethasone |
|---|---|
| STARTED | 19 |
| COMPLETED | 16 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | ASP7487, Velcade, Dexamethasone |
|---|---|
| Available drug expired on 31 May 16 | 3 |
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 | ASP7487, Velcade, Dexamethasone |
|---|---|---|
| Participants analysed | 19 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 |
| Age, Categorical: >=65 years | Participants | 7 |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 17 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Canada | Participants | 18 |
| Region of Enrollment: United States | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone, measured over 45 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligrams |
| Endpoint classification | not reduced to a single comparison |
The primary outcome measure is titled maximum tolerated dose of ASP7487 (OSI-906) with Velcade and dexamethasone. It is recorded as a numerical measure in milligrams, with a timeframe of 45 months. The registry description says that the Phase 1 objective was to determine the maximum tolerated dose of ASP7487 when combined with the recommended dose and schedule of bortezomib and dexamethasone. The outcome is therefore intended to capture dose-finding rather than a direct comparison of clinical outcomes between groups.
In general, dose-finding studies use escalating doses to identify a dose considered tolerable under the study’s rules. The maximum tolerated dose is meaningful only in relation to the rules used to define dose-limiting toxicity, the observation period, and how participants are assigned to dose levels. Those operational details are not reported in the registry record. The registry lists milligrams as the unit but does not state a numerical outcome value, specify which ASP7487 dose was selected, or give the method by which a maximum tolerated dose was determined.
The Phase 2 description separately names antitumor activity and objective response rate as aims at the dose established in Phase 1. That aim is not the primary outcome title, and the registry record does not report an objective response result. A stated endpoint or study objective should not be read as an observed finding: without the outcome data and analysis, the registry entry does not establish whether the dose-finding or activity objectives were met.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study design and selected safety counts, but it does not report the primary endpoint result. The outcome measure is maximum tolerated dose in milligrams, yet no dose value or dose-selection conclusion is present. The record also describes a Phase 2 objective of evaluating antitumor activity and establishing objective response rate, but gives no response estimate or analysis. Thus, the posted information does not quantify efficacy or show how precisely an efficacy estimate was measured.
There is no randomized comparison. Participants received the combination in a single group, so there is no concurrent control group against which to estimate a difference in outcomes. Even if an outcome were reported for the treated group, a within-group result alone would not isolate the contribution of ASP7487 from that of bortezomib, dexamethasone, prior treatment, or the course of the disease. The registry entry therefore does not support a comparative treatment effect.
The enrollment is listed as 19. The adverse-event record lists 19 at risk for other adverse events and 19 affected, and 19 at risk for serious adverse events with 8 affected. These are descriptive safety counts in the registry. They do not provide event timing, duration, severity grades beyond the serious-event classification, or a comparison with another group. The listed serious-event terms include lung infection and fever, each reported as 10.5%, as well as several terms reported as 5.3%. The record does not specify the event-level denominators or provide enough detail to interpret those percentages as comparative risks.
The record lists 2 deaths. It also includes death due to multiple myeloma among the serious adverse-event terms at 5.3%. These entries should be read as registry safety reporting, not as proof that treatment caused a death or as a complete account of causes of death. The relationship of individual events or deaths to treatment is not reported in the registry record.
In statistical terms, the principal limitation is not a wide or narrow confidence interval but the absence of a reported outcome estimate and analysis. No confidence interval, hypothesis test, or effect estimate is reported in the registry record. Without those, precision and statistical uncertainty for the primary outcome and the Phase 2 activity objective cannot be assessed. The terminated status is recorded, but it does not by itself explain why the study ended or establish whether its objectives were completed.
9. Statistical Methods Explained
The design determines which statistical questions can be addressed. This trial is recorded as a single-group study without randomization or masking. Participants received ASP7487 with bortezomib and dexamethasone; there is no separate control group in the registry record. As a result, the design can describe outcomes observed in the treated group if those outcomes are reported, but it cannot estimate a randomized contrast between the combination and another treatment. That distinction is important: an observed outcome in one group is not, by itself, evidence that the treatment caused the outcome.
What does dose escalation assess?
In general, dose escalation is a way to examine tolerability across dose levels and select a dose for further study. The Phase 1 description says that ASP7487 dose escalation was used to determine the maximum tolerated dose with bortezomib and dexamethasone. Interpreting such a result ordinarily depends on predefined rules for what counts as dose-limiting toxicity, the period during which toxicity is assessed, and the procedure for moving between doses. Those details are not reported in the registry record. The recorded primary outcome is a numerical dose in milligrams, but there is no reported value or selection rule in the posted results.
The regimen description names ASP7487 doses of 75, 100 and 150 mg BID. These are listed dose levels, not proof that all participants received every dose or that a particular dose was selected as the maximum tolerated dose. The registry record does not provide the allocation of participants across dose levels, dose-limiting toxicity counts by level, or a dose-escalation analysis. Those omissions prevent reconstruction of the dose-finding decision from the registry entry.
What can the Phase 2 objective show?
The Phase 2 description says that the combination at the maximum tolerated dose was to be evaluated for antitumor activity, with objective response rate as the stated aim. In general, an objective response rate is a proportion based on a defined set of response categories and an analysis population. Interpreting it requires the response criteria, the assessment schedule, the number of participants evaluable for response, and a clear definition of how missing or unevaluable assessments are handled. These details and any response estimate are not reported in the registry record.
A response proportion in a single group would describe the frequency of recorded responses in that group under the trial’s assessment rules. It would not on its own establish how that frequency compares with a different treatment or what would have happened to the same participants without the regimen. A comparative estimate generally requires a comparison group and an analysis that accounts for the study design. This trial has no randomized comparator in the registry record.
What do uncertainty measures mean?
In general, a confidence interval describes a range of estimates that are compatible with the observed data under the statistical model and its assumptions. It conveys uncertainty around an estimate; it does not guarantee that the true value lies in the interval, nor does it address biases caused by design or missing information. The registry record reports no confidence interval for the primary outcome or for response. Consequently, readers cannot use the posted results to judge the statistical precision of these outcomes.
A hypothesis test, when used, evaluates compatibility between data and a specified null model under stated assumptions. A p-value is not the probability that a treatment works, and it does not measure the size or clinical importance of an effect. No hypothesis-test result for the primary outcome or Phase 2 activity objective is reported in the registry record. The record also does not report a detailed statistical analysis plan, so it is not possible to determine whether such tests were planned or how they would have been specified.
How should planning calculations be understood?
In general, sample-size planning calculations illustrate how many participants might be needed under stated assumptions about the effect to detect, significance level, allocation, and statistical model. They are prospective planning exercises, not measurements of what happened in a trial. A calculation based on an observed effect is especially dependent on that effect estimate and should not be called observed power. The stated planning assumptions for this study context specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. They are planning assumptions, not evidence that this single-group trial used a two-arm design or those values to plan enrollment.
For time-to-event outcomes, a planning illustration may express the required information as an event count; other types may express participants per arm. Such illustrations do not change the actual study design, establish that the trial was adequately powered, or replace results from the enrolled group. The registry record does not report a trial-specific sample-size justification or a statistical plan connecting those planning assumptions to this study’s enrollment.
Why do the safety counts not establish comparative risk?
In general, safety counts are interpreted in relation to the population assessed, the period of observation, event definitions, and whether the count represents participants with at least one event or individual events. Serious adverse events and other adverse events are separate reporting categories. Counts in one treatment group can describe what was recorded there, but without a comparator they do not estimate an excess risk attributable to treatment. The registry record reports serious and other adverse-event counts, but does not include the fuller timing, grading, exposure, or comparative information needed for those interpretations.
Finally, statistical analysis depends on who is included. An intention-to-treat population, a safety population, and an evaluable population can differ, and each answers a different question. The registry record does not describe analysis populations for the primary outcome or Phase 2 activity objective. The safety entries do give their own at-risk counts, but those counts should not automatically be treated as the denominator for an unreported efficacy analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan describing multiplicity control, missing-data methods, or analysis populations for the efficacy objectives. It names a primary dose-finding outcome and also describes Phase 2 antitumor activity and objective response rate as aims. Without a plan, it is not possible to determine which analyses were prespecified as primary or secondary for inference, whether multiple comparisons or endpoints were anticipated, or how any resulting statistical uncertainty was handled.
In general, multiplicity arises when several outcomes, dose levels, time points, or subgroup comparisons are examined. Testing many questions can increase the chance of obtaining apparently notable findings by chance if the analysis does not account for the number and structure of those tests. That general concern does not establish that a particular multiplicity problem occurred in this trial; the registry record does not report enough information to assess the analyses that may have been conducted.
Missing-data handling also matters because incomplete outcome assessments can change the population contributing to an estimate and may bias results if missingness is related to outcomes. The record does not report how missing or unevaluable response assessments were handled, how withdrawals were treated, or whether any imputation method was used. It also does not identify the analysis population for the primary outcome or response objective.
The registry lists enrollment of 19 and safety at-risk counts, but these do not define the analysis population for each efficacy question. Without participant flow, outcome availability, and analysis methods, the representativeness and precision of any unreported efficacy result cannot be evaluated. No assumptions about the missing-data or multiplicity procedures should be inferred from the trial’s phase or design.
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 |
|---|---|---|---|
| ASP7487, Velcade, Dexamethasone | 8 | 19 | 42.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ASP7487, Velcade, Dexamethasone | 2 of 19 |
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 |
|---|---|
| ASP7487, Velcade, Dexamethasone | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | ASP7487, Velcade, Dexamethasone |
|---|---|---|
| Lung infection | Infections and infestations | 2 of 19 |
| fever | General disorders | 2 of 19 |
| Alanine Aminitransferase Increased | Investigations | 1 of 19 |
| Asparate Aminotransferase increased | Investigations | 1 of 19 |
| Delirium | Nervous system disorders | 1 of 19 |
| Death due to multiple myeloma | General disorders | 1 of 19 |
| Cardiac arrest | Cardiac disorders | 1 of 19 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 19 |
| dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ASP7487, Velcade, Dexamethasone |
|---|---|---|
| Platelet count decreased | Investigations | 13 of 19 |
| Nausea | Gastrointestinal disorders | 8 of 19 |
| Creatinine Increased | Investigations | 8 of 19 |
| Anemia | Blood and lymphatic system disorders | 7 of 19 |
| Diarrhea | Gastrointestinal disorders | 7 of 19 |
| Fatigue | General disorders | 7 of 19 |
| Neuropathy | Nervous system disorders | 6 of 19 |
| Cough | Respiratory, thoracic and mediastinal disorders | 6 of 19 |
| Pneumonia/influenza | Infections and infestations | 4 of 19 |
| Headache | Nervous system disorders | 4 of 19 |
Serious events with the highest arm-level rate: lung infection (10.5%), fever (10.5%), alanine aminitransferase increased (5.3%), asparate aminotransferase increased (5.3%), delirium (5.3%).
The registry reports serious adverse events for a group with 19 at risk and 8 affected. For other adverse events, it reports 19 at risk and 19 affected. It also lists 2 deaths. These counts describe the safety information recorded for the single treatment group; they do not compare the regimen with another treatment or establish that treatment caused an event.
Among the serious-event terms, lung infection and fever are each listed at 10.5%. Alanine Aminitransferase Increased, Asparate Aminotransferase increased, delirium, and death due to multiple myeloma are each listed at 5.3%. The registry record does not provide the event-level denominators, timing, duration, or individual treatment attribution for these terms. The percentages should therefore be read as registry-reported summaries, not as comparative risks or as a complete account of all safety outcomes.
In general, a participant-level count of people with at least one serious event differs from a count of event episodes: one participant may experience more than one event. The record does not clarify the event-level counting details for these terms. Nor does it report exposure duration or a control group, both of which would matter for broader safety comparisons. The listed deaths should not be attributed to the study treatment based on these entries alone.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 1/2, open-label, non-randomized, single-group study was registered for ASP7487 with bortezomib and dexamethasone in relapsed or relapsed/refractory multiple myeloma. It describes Phase 1 dose escalation and a Phase 2 expansion intended to evaluate antitumor activity at the dose established in Phase 1. It also records an enrollment of 19, a terminated status, and selected adverse-event counts.
It does not report the numerical maximum tolerated dose, the outcome of the dose-finding process, an objective response rate, or an efficacy analysis. Therefore, the record does not show whether the primary endpoint was met or how much uncertainty surrounds any efficacy result. A stated objective is not an observed result, and the trial’s status alone does not establish why it ended or whether its objectives were completed.
The design also limits what a result from this study could establish. Without randomization or a concurrent control group, outcomes in the treated group cannot provide a direct estimate of the difference between the combination and another treatment. An observed response, if one were reported, could describe the treated group but would not by itself show how outcomes would differ under another option. The record does not provide an analysis that addresses that comparative question.
The safety entries identify reported serious adverse events, other adverse events and deaths, but do not establish treatment causation. They are not a substitute for detailed event descriptions, timing, exposure information, or comparative safety data. The record also lacks a reported analysis plan, response assessment details, and descriptions of missing data and analysis populations. These gaps constrain interpretation of both efficacy and safety.
In general, a trial can contribute useful information even when it cannot answer every comparative question. Dose-finding and early activity objectives can inform later research when their methods and results are reported. For this registry entry, however, the available information supports description of the planned aims and recorded safety counts, not conclusions about the magnitude or precision of an efficacy effect.
13. Why This Trial Matters Statistically
This study is statistically notable because it combines an early-phase dose-finding objective with a later activity objective in a single-group design. Those aims require different interpretations. Dose escalation concerns tolerability and selection of a dose under specified rules, while evaluating objective response concerns the frequency of responses under defined assessment criteria. The registry describes both aims but does not report results for either.
The design also illustrates the distinction between an outcome within a treated group and a treatment effect relative to a control. A single-group study can describe observed outcomes, but it has no concurrent comparison to separate the combination’s contribution from other influences. This matters particularly in a population described as having relapsed or relapsed/refractory multiple myeloma, where the registry does not provide participant-level clinical details or an alternative-treatment group.
Another statistical lesson is that a listed endpoint is not enough to assess evidence. Interpretation depends on its operational definition, analysis population, missing-data rules, and uncertainty estimates. The primary measure is maximum tolerated dose in milligrams, but the registry does not give the dose result or the rules used to select it. The Phase 2 objective is described, but no response estimate or analysis is reported. Without these elements, neither the result nor its precision can be evaluated.
The safety information similarly demonstrates why event counts need context. Counts and percentages from a single treatment group can convey what the registry recorded, but cannot establish comparative safety or treatment causation. Details about event timing, exposure, severity, and attribution would be needed for fuller interpretation, and are not reported in the registry record.
Finally, the terminated status makes transparent reporting of trial outcomes especially relevant, but the record does not state the reason for termination. Statistical interpretation must remain bounded by what is reported: design, aims, and selected safety summaries, rather than unreported results or explanations.
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 trial-specific limitation is the single-group, non-randomized design. There is no concurrent control arm, so the study cannot estimate a randomized difference between the combination and another treatment. Open-label conduct also means the study was not masked; the registry does not report safeguards that might have been used for outcome assessment.
The registry lists enrollment of 19 but does not report participant characteristics, dose-level enrollment, duration of treatment, or participant flow. It does not state how many people contributed to each efficacy outcome or whether all enrolled participants were evaluable. As a result, the relationship between the enrolled group and any analysis population cannot be assessed.
The record identifies maximum tolerated dose as the primary outcome but provides no result, operational definition of dose-limiting toxicity, or account of the dose-escalation decision. The Phase 2 objective of evaluating antitumor activity and objective response rate is described without response criteria, assessment details, an estimate, or an uncertainty interval. The statistical analysis plan, multiplicity approach, missing-data methods, and sample-size justification are not reported in the registry record.
Safety reporting is also limited to summary counts and selected serious-event terms. The record does not report detailed event timing, duration, severity grading, treatment attribution, or exposure-adjusted comparisons. The 2 deaths are listed without enough information to assess their relationship to study treatment. The reason for the terminated status is not reported in the registry record, so no explanation for the trial ending should be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma — NCT01672736.
- Registry record last updated 2018-09-13; status last verified 2018-09.
- Results first posted 2018-09-13.
- 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
This registry entry concerns a multicenter, open-label, non-randomized, single-group Phase 1/2 trial of ASP7487 (OSI-906) with bortezomib and dexamethasone for relapsed or relapsed/refractory multiple myeloma. Enrollment is listed as 19. The trial began in 2012-09, had a primary completion date of 2017-03-27, and is recorded as terminated.
The primary outcome is maximum tolerated dose in milligrams, with a timeframe of 45 months. Phase 1 was described as dose escalation; Phase 2 was intended to assess antitumor activity and objective response rate at the dose established in Phase 1. Neither an endpoint result nor an efficacy analysis is reported in the registry record.
The safety record lists 8 affected by serious adverse events among 19 at risk, 19 affected by other adverse events among 19 at risk, and 2 deaths. Serious-event terms and percentages are reported, but the record does not provide comparative safety information or establish treatment causation.