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 Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS (NCT02706899), a randomized phase 1, phase 2 study. The primary outcome is Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02706899 |
| Phase | Phase 1, Phase 2 |
| Condition | Myelodysplastic Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Seagen Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with previously untreated myelodysplastic syndrome classified as International Prognostic Scoring System Intermediate-2 or high risk. The registry record describes the study population as having higher-risk disease.
Intervention
Vadastuximab talirine, also identified as SGN-CD33A or 33A, given in combination with azacitidine. The safety groups are identified by 33A doses of 5 mcg/kg and 10 mcg/kg, each with azacitidine.
Comparator
The registry describes a placebo for 33A combined with azacitidine as an arm. The posted safety-group details cover the two 33A dose groups, not a placebo group; placebo-group outcome figures are not reported in the registry record.
Primary question
The phase 1 primary outcome was whether a recommended vadastuximab talirine dose could be identified for the phase 2 portion. The record says no recommended dose was identified because the study was terminated; dose delays and reductions are reported in lieu of a dose recommendation.
The study addressed a dose-selection question within a phase 1/2 trial, rather than presenting a single comparative estimate of clinical benefit. Its listed secondary outcomes include safety, response, progression-free survival, transformation to acute myeloid leukemia, and overall survival. Numerical results for those secondary efficacy outcomes are not reported in the registry record.
The record identifies the study as randomized, quadruple-masked, and parallel. Those design labels describe the intended allocation and masking structure, but do not establish what comparisons can be estimated from the posted outcome information. Enrollment was 19, and the study status is terminated.
3. Trial Design
This was a phase 1/2, randomized, quadruple-masked, parallel study of vadastuximab talirine plus azacitidine in patients with previously untreated IPSS Intermediate-2 or high-risk myelodysplastic syndrome. The registry lists vadastuximab talirine, azacitidine, and placebo for 33A among the interventions. Its arm descriptions identify 33A plus azacitidine and placebo plus azacitidine. Safety details are posted for 33A at 5 mcg/kg with azacitidine and 33A at 10 mcg/kg with azacitidine.
Randomization means that allocation was described as random; the registry record does not report the sequence-generation method, allocation concealment procedures, or the roles masked under quadruple masking. A parallel model indicates that the arms were designed to be followed as separate groups rather than as a crossover. The record does not report treatment schedules or the duration of individual treatment.
The study began in 2016-02, and its primary completion date is listed as 2017-11-06. The status is terminated. Enrollment is recorded as 19. The registry record does not report a reason for termination beyond noting that the recommended dose was not identified due to study termination. It also does not report a target enrollment or the planned duration of follow-up.
The primary outcome was a phase 1 dose-selection measure, with a timeframe of up to 1 year. The registry lists several secondary outcomes, including adverse events and laboratory abnormalities, complete response, hematologic improvement, duration of response, progression-free survival, transformation to acute myeloid leukemia, and overall survival. The posted information does not give a single comparative analysis covering these outcomes.
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 | 33A (5 mcg/kg) + Azacitidine | 33A (10 mcg/kg) + Azacitidine |
|---|---|---|
| STARTED | 13 | 6 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 13 | 6 |
Reasons for not completing this period:
| Reason | 33A (5 mcg/kg) + Azacitidine | 33A (10 mcg/kg) + Azacitidine |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Death | 8 | 0 |
| Study Termination by Sponsor | 4 | 6 |
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 | 33A (5 mcg/kg) + Azacitidine | 33A (10 mcg/kg) + Azacitidine | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 6 | 19 | |
| Age, Continuous | years | 72 (46 to 83) | 66 (57 to 81) | 72 (46 to 83) |
| Sex: Female, Male: Female | Participants | 6 | 2 | 8 |
| Sex: Female, Male: Male | Participants | 7 | 4 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 6 | 19 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 1 | 4 |
| Race (NIH/OMB): White | Participants | 10 | 5 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 13 | 6 | 19 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: Grade 0: Normal activity | Participants | 6 | 2 | 8 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: Grade 1: Symptoms but ambulatory | Participants | 6 | 4 | 10 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: Grade 2: In bed less than 50% of the time | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study, measured over Up to 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of doses |
| Endpoint classification | not reduced to a single comparison |
The primary outcome was the recommended dose of vadastuximab talirine for the phase 2 portion of the study, with the outcome unit described as number of doses and a timeframe of up to 1 year. This is a dose-selection endpoint: its purpose is to identify a dose to carry forward, rather than to quantify a treatment effect on a clinical outcome such as response or survival.
The registry record explicitly states that a recommended dose was not identified in phase 1 because the study was terminated. It says that the number of dose delays and reductions is reported in lieu of a dose recommendation. The numerical counts of delays and reductions are not reported in the registry record, so the primary outcome cannot be interpreted as a dose recommendation or as a numerical comparison between dose groups.
In general, dose selection in an early-phase study can use information about tolerability and treatment delivery to decide which dose merits further study. That general purpose should not be confused with evidence of comparative efficacy. Here, the record does not report a selected phase 2 dose, nor does it provide a single estimate of benefit associated with either dose.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central primary-outcome result is that no recommended dose of vadastuximab talirine was identified for the phase 2 portion, with study termination given as the reason. Dose delays and reductions are described as reported in lieu of a recommendation, but their numerical results are not reported in the registry record. Consequently, the primary endpoint does not support a dose-selection conclusion from the posted figures.
The study was randomized and parallel, but the posted results do not give a single comparative estimate for the primary endpoint. The primary measure is itself a dose-selection outcome, and the registry notes that it has several categories or time points and is not reduced to one comparison. Randomization is a design feature, not a substitute for reporting group-level outcome data or an analysis. The registry also lists no analyses. This does not establish that no analyses were conducted; it means that analyses are not listed in the registry record.
Enrollment was 19. The adverse-event information includes serious events, other adverse events, and deaths for the two listed 33A dose groups. These figures are descriptive counts, not estimates adjusted for differences in follow-up or patient characteristics. The record does not provide a placebo-plus-azacitidine safety group in the posted adverse-event details, so those details do not permit a direct safety comparison with placebo plus azacitidine.
The registry lists response and time-to-event outcomes, including complete response, hematologic improvement, duration of response, progression-free survival, transformation to acute myeloid leukemia, and overall survival. Numerical results for these outcomes are not reported in the registry record. It is therefore not possible to use the posted information to quantify treatment effects on response or survival, or to assess their precision with confidence intervals.
In general, an estimate is more informative when its uncertainty is reported alongside it. A confidence interval describes a range of values compatible with the data under the analysis assumptions; it does not guarantee that the true effect lies within that interval. No confidence intervals or comparative effect estimates are reported for the primary outcome in the registry record. The appropriate statistical reading is therefore limited: the study ended without a recommended dose identified, and the posted information does not establish comparative efficacy or comparative safety.
9. Statistical Methods Explained
What does randomization contribute?
The registry describes allocation as randomized. In general, random allocation aims to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics at the start of a study. It does not ensure that groups are identical, particularly when enrollment is limited, and it does not by itself show that a treatment caused an observed outcome. Estimation still depends on having outcome data, a defined comparison, and an analysis appropriate to the design.
The record does not report how the random sequence was generated or how allocation was concealed. It labels the study quadruple-masked, but does not identify which groups of people were masked or describe how masking was maintained. Those details are not reported in the registry record, so the design labels cannot be expanded into more specific claims about study procedures.
What does the primary outcome measure?
The phase 1 outcome concerns identifying a recommended dose for the phase 2 portion. The registry says no recommended dose was identified because the study was terminated, and that dose delays and reductions were reported in lieu of a dose recommendation. This differs from an efficacy endpoint: dose selection is intended to guide which dose to take forward, while efficacy endpoints describe outcomes such as response or survival. The numerical delay and reduction results are not reported in the registry record.
The primary outcome is not reduced to one comparison because it has several categories or time points. In general, a single summary can simplify interpretation, but combining categories or time points requires clear definitions and a prespecified method. Without the component results and analysis details, it is not possible to reconstruct a single estimate or determine how different categories contributed to a decision.
How should uncertainty be considered?
In general, an estimate describes the observed result, while a standard error or confidence interval conveys its sampling uncertainty under specified assumptions. A confidence interval can help readers judge how much precision the data support, but it cannot correct bias, missing outcome data, or an inappropriate analysis. The registry record does not report confidence intervals for the primary outcome or a comparative effect estimate for it.
For event counts, the amount of information depends on the number of observed events and the way participants were followed. A proportion based on a small group can change substantially when a small number of observations differ. Enrollment was 19, but that total does not reveal the precision of any particular outcome estimate, and the posted information does not provide uncertainty intervals for the adverse-event figures.
What can be learned from the parallel design?
In general, a parallel design assigns participants to a study arm and assesses outcomes by assigned group. It avoids the within-person treatment-period comparisons used in a crossover design, but interpretation still depends on allocation, follow-up, adherence, and analysis choices. The registry record labels this study parallel, but does not report treatment schedules, follow-up completeness, or an analysis population for the posted outcomes.
Masking and randomization address different sources of potential bias. Randomization concerns how treatment groups are formed; masking can reduce the influence of treatment knowledge on care, outcome assessment, or reporting. The registry's quadruple-masked label does not specify which people were masked, so the reader cannot assess those roles from the registry record alone.
Are planning calculations equivalent to observed power?
No. In general, a planning calculation describes a hypothetical design under stated assumptions; it is not a measure of the probability that an observed result is true. The record does not report a trial-specific sample-size justification or a statistical plan that would connect planning assumptions to the study's design. Any planning illustration based on an observed effect should be read as a hypothetical calculation, not as observed power or as evidence that the study had adequate precision.
The registry record lists no analyses. This should not be interpreted as proof that statistical analyses were never performed. It means that the registry information does not describe analysis methods, model specifications, adjustment factors, handling of repeated assessments, or an approach to multiple outcomes. Those omissions limit reproducibility and make it inappropriate to infer an unreported method from the design labels or outcome names.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 9 outcome measures and 0 analyses. The named secondary outcomes cover safety and laboratory abnormalities, complete response, hematologic improvement, duration of response, progression-free survival, transformation to acute myeloid leukemia, and overall survival. The primary outcome also involves multiple categories or time points and is not reduced to one comparison.
When a study assesses several outcomes or several comparisons, the chance of at least one apparently notable result can increase if each is interpreted without accounting for multiplicity. In general, a prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory analyses can help readers understand how to interpret multiple tests. The registry record does not report a multiplicity strategy, hypothesis hierarchy, or statistical analysis plan. No claim can therefore be made about whether or how multiplicity was handled.
The registry record does not report how missing outcome data were handled, whether follow-up was complete, or which analysis populations were used. It also does not report whether analyses were based on assigned treatment, treatment received, or another population definition. These details matter because exclusions and incomplete follow-up can affect the results and the interpretation of comparisons. The absence of those descriptions in the record does not establish that data were missing or that a particular population was used; it means those matters are not reported in the registry record.
Because no analysis results are listed, there are no reported p-values or comparative estimates to assess for multiplicity or missing-data sensitivity. The listed outcomes describe what was intended for assessment, not numerical findings for each endpoint.
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 |
|---|---|---|---|
| 33A (5 mcg/kg) + Azacitidine | 9 | 13 | 69.2% |
| 33A (10 mcg/kg) + Azacitidine | 4 | 6 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 33A (5 mcg/kg) + Azacitidine | 8 of 13 |
| 33A (10 mcg/kg) + Azacitidine | 0 of 6 |
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 |
|---|---|
| 33A (5 mcg/kg) + Azacitidine | 13 of 13 |
| 33A (10 mcg/kg) + Azacitidine | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | 33A (5 mcg/kg) + Azacitidine | 33A (10 mcg/kg) + Azacitidine |
|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 4 of 13 | 4 of 6 |
| Pneumonia | Infections and infestations | 2 of 13 | 0 of 6 |
| Pancytopenia | Blood and lymphatic system disorders | 1 of 13 | 0 of 6 |
| Cellulitis | Infections and infestations | 1 of 13 | 0 of 6 |
| Respiratory syncytial virus infection | Infections and infestations | 1 of 13 | 0 of 6 |
| Sepsis | Infections and infestations | 1 of 13 | 0 of 6 |
| Nausea | Gastrointestinal disorders | 1 of 13 | 0 of 6 |
| Vomiting | Gastrointestinal disorders | 1 of 13 | 0 of 6 |
| Dehydration | Metabolism and nutrition disorders | 1 of 13 | 0 of 6 |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 13 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 33A (5 mcg/kg) + Azacitidine | 33A (10 mcg/kg) + Azacitidine |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 13 | 4 of 6 |
| Constipation | Gastrointestinal disorders | 6 of 13 | 4 of 6 |
| Anaemia | Blood and lymphatic system disorders | 6 of 13 | 4 of 6 |
| Fatigue | General disorders | 6 of 13 | 3 of 6 |
| Headache | Nervous system disorders | 4 of 13 | 3 of 6 |
| Dizziness | Nervous system disorders | 3 of 13 | 3 of 6 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 13 | 1 of 6 |
| Diarrhoea | Gastrointestinal disorders | 2 of 13 | 3 of 6 |
| Thrombocytopenia | Blood and lymphatic system disorders | 5 of 13 | 0 of 6 |
| Pyrexia | General disorders | 3 of 13 | 2 of 6 |
Serious events with the highest arm-level rate: febrile neutropenia (66.7%), pneumonia (15.4%), pancytopenia (7.7%), cellulitis (7.7%), respiratory syncytial virus infection (7.7%).
The registry reports serious adverse events for the 33A (5 mcg/kg) plus azacitidine group with 13 participants at risk and 9 affected, and for the 33A (10 mcg/kg) plus azacitidine group with 6 at risk and 4 affected. For other adverse events, the corresponding figures are 13 at risk and 13 affected in the 5 mcg/kg group, and 6 at risk and 6 affected in the 10 mcg/kg group. Deaths are listed as 8 and 0, respectively. These are descriptive figures; the registry record does not state that the deaths were caused by treatment.
The listed serious adverse-event terms include febrile neutropenia at 66.7%, pneumonia at 15.4%, and pancytopenia, cellulitis, respiratory syncytial virus infection, and sepsis at 7.7% each. These percentages should be read as reported, not combined into a total. In general, one participant may experience more than one event type; the registry record does not clarify whether term categories overlap or provide term-level counts alongside these percentages.
The adverse-event details posted for interpretation do not include a placebo-plus-azacitidine group. They therefore do not establish a comparative safety difference between active treatment and placebo. The record also does not provide confidence intervals or a description of follow-up for these figures, limiting assessment of their precision and comparability.
12. What the Result Does, and Does Not, Mean
The posted primary-outcome statement is specific: a recommended vadastuximab talirine dose for the phase 2 portion was not identified because the study was terminated. The registry says that dose delays and reductions were reported instead, but their numerical values are not reported in the registry record. This is not a reported dose recommendation, nor is it an estimate of a treatment effect on response or survival.
The registry includes several efficacy-related outcomes, but their numerical results are not reported in the registry record. The posted information therefore cannot establish the size or direction of an effect on complete response, hematologic improvement, duration of response, progression-free survival, transformation to acute myeloid leukemia, or overall survival. It also cannot establish that there was no effect: absence of numerical results in the record is not evidence of a null result.
The safety figures describe events in the two listed 33A dose groups. They are not a direct comparison against placebo plus azacitidine, because placebo-group safety figures are not reported in the posted details. Death counts are not, by themselves, evidence that treatment caused those deaths. Attribution and comparative interpretation require information that is not reported in the registry record.
In general, a randomized design can support comparative inference when outcomes and analysis methods are reported and when the relevant assumptions are reasonable. The randomized label alone does not supply missing estimates, uncertainty intervals, or details about outcome follow-up. With enrollment of 19 and no listed analyses, interpretation should remain descriptive and limited to the reported record rather than extending to claims about efficacy or comparative safety.
13. Why This Trial Matters Statistically
This trial is statistically notable because its main phase 1 question was dose selection, but the registry reports that no recommended dose was identified before study termination. That outcome illustrates an important distinction: an early-phase study can be designed to identify a dose for later study, yet its recorded result may not yield a dose recommendation. Without numerical dose-delay and dose-reduction results, readers cannot examine the evidence that would have informed dose selection.
The randomized, quadruple-masked, parallel design supplies important context, but design labels do not replace outcome reporting. The registry lists a placebo-plus-azacitidine arm, while the posted adverse-event details describe only the two vadastuximab talirine dose groups. This gap matters for comparative interpretation: descriptive event counts in active-treatment groups alone do not quantify how outcomes differ from the comparator.
The study also lists multiple secondary outcomes spanning safety, response, and survival. Those outcomes can answer different questions and may have different follow-up and analysis requirements. The record lists no analyses and does not report a statistical plan, so the reader cannot evaluate how the outcomes were prioritized, how multiplicity was addressed, or how incomplete observations were handled.
More broadly, the record demonstrates why conclusions depend on both design and reporting. Randomization can support a comparison, but only when the comparison and its uncertainty are reported. The termination status, lack of a recommended dose, and absence of numerical secondary efficacy results sharply limit what can be inferred from the posted information.
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 registry record does not report a reason for termination beyond linking termination to the failure to identify a recommended dose. It does not give numerical counts for dose delays or reductions, so the primary endpoint cannot be examined in detail. It also does not provide a selected dose for the phase 2 portion.
Although the study is described as randomized and quadruple-masked, the sequence-generation procedure, allocation concealment, and identities of the masked groups are not reported in the registry record. Treatment schedules and the duration of individual follow-up are also not reported. The primary outcome has multiple categories or time points and is not reduced to a single comparison, which limits concise comparative interpretation.
The registry lists 9 outcome measures and 0 analyses, but numerical results for the secondary efficacy outcomes are not reported in the registry record. No analysis plan, multiplicity approach, missing-data method, or analysis-population definition is reported. The adverse-event figures cover two active-dose groups; corresponding placebo-plus-azacitidine safety details are not reported in the posted information. Confidence intervals and comparative estimates are not reported for these outcomes.
Enrollment was 19. The registry does not report a target enrollment or a trial-specific sample-size justification. These limitations do not show that analyses or procedures were absent; they define what cannot be assessed from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS — NCT02706899.
- Registry record last updated 2019-02-12; status last verified 2019-01.
- Results first posted 2018-12-21.
- 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
NCT02706899 is a phase 1/2 randomized, quadruple-masked, parallel study of vadastuximab talirine plus azacitidine in previously untreated IPSS Intermediate-2 or high-risk myelodysplastic syndrome. The record lists enrollment of 19, a start date of 2016-02, primary completion on 2017-11-06, and terminated status.
The primary outcome was selection of a recommended vadastuximab talirine dose for phase 2, with dose delays and reductions reported in lieu of a recommendation. The registry states that no recommended dose was identified because the study was terminated. It lists 9 outcome measures and 0 analyses. Numerical results for the secondary efficacy outcomes, as well as numerical dose-delay and dose-reduction results, are not reported in the registry record.