Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS) (NCT01700335), a na phase 1 study. The primary outcome is Number of Participants Who Experienced Dose-limiting Toxicities (DLTs).

2. Clinical Question

The study's stated purpose was to investigate tolerability, determine dose-limiting toxicity and the maximum tolerated dose, and estimate a recommended dose for phase II studies. Pharmacokinetics and antitumor effects were also intended to be investigated. These aims place the study in an early-phase, dose-finding context: the central question concerns tolerability at the tested doses, rather than a comparison of treatment with an independent control.

The registry record identifies two dose groups, but it does not describe a randomized comparison between them. Differences in outcomes across those groups therefore cannot be read as the effect of one dose versus another under controlled, like-for-like conditions. The record reports 3 participants at risk in the 1200 mg/day group and 6 in the 1800 mg/day group for the adverse-event summaries. Those small group counts make event counts especially important to interpret cautiously.

The primary endpoint is a participant count for dose-limiting toxicity, with the definition tied to specified adverse-event criteria and observation through Cycle 2. Although that endpoint is named, its result is not reported in the registry record. The record also lists hematologic remission and hematologic improvement as secondary outcomes, with response-duration requirements under IWG 2006 criteria. Their results are not reported in the registry record either. Thus, the stated clinical question can be described, but the posted results do not answer it with a reported primary endpoint count.

3. Trial Design

This is a Phase I clinical trial sponsored by SymBio Pharmaceuticals. The registry record classifies it as a single-group study, with allocation listed as NA and masking as none. It reports 9 participants enrolled. The study is marked completed, with a start date of 2012-06 and primary completion in 2015-02.

SyB L-1101 is the listed intervention. The study description identifies a 1200 mg/day cohort and an 1800 mg/day cohort. For the 1200 mg/day group, it reports intravenous administration for 3 consecutive days followed by an 11-day observation period. The record identifies the 1800 mg/day group, but a complete administration description for that cohort is not reported in the registry record. The adverse-event summaries give 3 participants at risk in the 1200 mg/day group and 6 in the 1800 mg/day group.

The design is not a randomized, controlled comparison. The dose groups are cohorts within a single-group study, not independently assigned intervention and control arms. Consequently, a difference between their observed event counts would be descriptive; it would not by itself isolate a causal dose effect. Enrollment and event counts also offer limited precision for estimating event rates, particularly when a small change in the number of participants with an event would substantially alter the observed count.

The primary outcome is the number of participants who experienced dose-limiting toxicities, with a timeframe listed as up to 60 weeks. The definition specifies qualifying events occurring by the final observation in Cycle 2 and states that the Efficacy and Safety Assessment Committee was also to assess DLTs. The relationship between the broad timeframe and the Cycle 2 criterion is not further explained in the registry record. A detailed statistical analysis plan, including the planned approach to comparing cohorts, is not reported in the registry record.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Dose-limiting Toxicities (DLTs), measured over Up to 60 weeks.

The primary endpoint is the number of participants who experienced dose-limiting toxicities (DLTs). It is a count of participants meeting a clinical event definition, rather than a measurement of average change in a laboratory value or time until an event. The registry record lists the endpoint timeframe as up to 60 weeks and defines DLTs by qualifying adverse events occurring by the final observation in Cycle 2. It also says DLTs were to be assessed by the Efficacy and Safety Assessment Committee.

The definition includes Grade 3 or higher non-hematologic toxicity, with specified exceptions, and certain Grade 3 or higher mouth, esophageal, or swallowing toxicities that persist for >= 4 days. The record further describes conditions under which some otherwise excluded symptoms qualify. These criteria matter because the endpoint is not simply a count of all adverse events: it is a count based on severity, duration, causal attribution, and the stated assessment process.

In general, DLT endpoints are used in early-phase studies to summarize treatment-limiting toxicity during a defined observation window and inform dose selection. They do not, on their own, measure antitumor benefit. The registry record does not report the number of participants meeting the DLT definition, so the primary endpoint's observed result cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: each participant either met the DLT definition or did not, within the specified assessment window. The posted endpoint is not a continuous measurement. For a binary outcome, descriptive reporting commonly includes both the number of participants with the event and the number assessed. Those quantities help readers distinguish an event count from its denominator. Here, the registry record does not report the primary endpoint count or an analysis of it, so a DLT frequency or uncertainty estimate cannot be interpreted.

In general, a proportion is the number of participants with an event divided by the number observed for that outcome. With small denominators, proportions can be unstable: one participant's status can noticeably alter the estimate. This is one reason to consider uncertainty alongside a point estimate. A confidence interval gives a range of values that, under its method and assumptions, represents uncertainty about the underlying event frequency. The registry record does not report a confidence interval for the primary outcome. No numerical interval should be inferred from the adverse-event summaries, which are separate from the primary DLT endpoint.

DLT classification also depends on the endpoint definition, not solely on the label of an adverse event. The registry description includes severity thresholds, duration criteria for specified toxicities, exclusions and exceptions, and an assessment by the Efficacy and Safety Assessment Committee. General statistical interpretation therefore depends on applying those criteria consistently to the relevant observation period. The record states that qualifying events occurred by the final observation in Cycle 2 and gives a timeframe of up to 60 weeks, but it does not provide further detail explaining how those timing descriptions relate to one another.

The study is described as single group, with no masking and allocation listed as NA. Its dose cohorts are not a randomized comparison. In general, randomized allocation helps balance known and unknown factors between groups, while an uncontrolled cohort comparison can be affected by differences in participant characteristics, care, exposure, or observation. The registry record does not report a formal adjusted comparison between the dose cohorts. Their adverse-event counts are therefore best treated as descriptive group summaries, not as estimates of a causal effect of dose.

The adverse-event results distinguish serious events from other adverse events. In general, these categories are not interchangeable: the serious-event summary captures events classified as serious, while the other-event summary is a separate category in the registry reporting. Neither category is synonymous with the DLT endpoint, whose definition uses its own criteria. A serious event is not automatically a DLT, and a DLT result cannot be inferred by adding or relabeling adverse-event counts. The record does not provide participant-level overlap among these categories.

The registry record lists 4 outcome measures and 0 analyses. It identifies hematologic remission and hematologic improvement as secondary outcomes, requiring responses to be sustained for at least 4 weeks and at least 8 weeks, respectively, under IWG 2006 criteria. It does not report results for these outcomes, nor does it provide inferential analyses of the primary endpoint. In general, reporting a duration requirement defines how a response qualifies; it does not itself establish that a response occurred or how often it occurred.

Multiplicity refers generally to the interpretive issue that arises when multiple outcomes or hypotheses are examined. Testing many outcomes can increase the chance that at least one finding appears notable by chance, depending on the analysis and decision rules. A statistical plan may address this through prespecified outcome hierarchy, adjustment, or other approaches, but the registry record does not report whether any multiplicity strategy was planned. No adjustment should be assumed, and no claim about statistical significance can be made from the outcomes listed without analysis results.

The sample-size assumptions describe planning illustrations based on the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such estimates are planning scenarios, not observed power and not a description of the actual single-group cohort design. The registry record does not report the trial's sample-size justification. No sample-size estimate can be reconstructed for the primary endpoint from the posted record because its result is not reported.

In general, a significance level is a prespecified criterion used in certain hypothesis-testing procedures; it is not a guarantee that a result is true or clinically important. A normal approximation is a mathematical simplification that can be used for some planning calculations. Whether such an approximation is suitable depends on the setting and assumptions. The planning assumptions do not establish that this was the analysis used for trial outcomes, and the registry record does not report an inferential analysis plan for those outcomes.

Over-dispersion is a general issue for count data when observed variation exceeds what a statistical model assumes. It is not a specific reported finding in this trial, and the DLT endpoint is described as a participant count rather than a repeated-event count. More broadly, data structure matters: multiple events in one participant, variable follow-up, or differing opportunities for observation can complicate interpretation. The registry record does not report enough participant-level information or analytic detail to assess such features for the posted outcomes.

Missing-data methods describe how an analysis handles outcomes that are unavailable for some participants. The registry record does not report a missing-data strategy or analysis populations. It is therefore not possible to determine from the record whether all enrolled participants were included in each outcome analysis, how incomplete follow-up was handled, or whether the number assessed differed from the number at risk. The adverse-event denominators are reported, but they do not resolve those questions for the DLT endpoint.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("SyB L-1101 1200 mg/Day Group", "SyB L-1101 1800 mg/Day Group")
n      <- c(3, 6)
events <- c(0, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  SyB L-1101 1200 mg/Day Group  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  SyB L-1101 1800 mg/Day Group  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures, including the primary DLT count and secondary outcomes for hematologic remission and hematologic improvement under IWG 2006 criteria. It does not report results for those secondary outcomes. Because several outcomes are identified, multiplicity is relevant as a general interpretive consideration: when multiple outcomes are analyzed, a statistical plan may specify which result is primary and whether any adjustment or hierarchy will guide interpretation. The registry record does not report a multiplicity strategy, so none should be assumed.

The record lists 0 analyses. It does not report an analysis plan, including the statistical procedures intended for the primary endpoint, how dose cohorts would be compared, or whether estimates would be adjusted for participant characteristics. It also does not report a sample-size justification. The sample-size assumptions describe planning illustrations, rather than the trial's own design, and should not be treated as evidence that the study had a particular probability of detecting an effect.

Missing-data handling and analysis populations are not reported in the registry record. The reported adverse-event denominators identify participants at risk for those summaries, but the record does not specify the population used for the primary endpoint or whether all enrolled participants were assessed for it. It also does not state how incomplete outcome observations or withdrawals, if any, were handled. These details matter because the denominator and rules for inclusion shape the interpretation of a participant count.

The primary DLT result itself is not reported, so the effect of missingness or analytical choices on that result cannot be evaluated. In general, the absence of a reported analysis is not proof that no analysis was conducted; it means that the registry record does not provide one for readers to assess.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: meningitis (16.7%), sepsis (16.7%), device related infection (16.7%), pneumonia bacterial (16.7%).

The serious adverse-event summary reports 0 participants affected among 3 at risk in the 1200 mg/day group, and 2 participants affected among 6 at risk in the 1800 mg/day group. The separate summary for other adverse events reports 3 participants affected among 3 at risk in the 1200 mg/day group and 6 among 6 at risk in the 1800 mg/day group. These are descriptive counts for the listed groups; because the study was not a randomized comparison, they do not establish that dose caused any difference between groups.

The serious adverse-event terms listed are meningitis, sepsis, device related infection, and pneumonia bacterial, each with a reported incidence of 16.7%. The record does not give corresponding event counts or explain participant-level overlap among terms. The percentages should be read as the registry's reported values, not combined or used to infer how many distinct participants experienced serious events. Deaths are not reported in the registry record.

Serious adverse events and DLTs are distinct summaries. The primary DLT definition includes specific criteria for severity, duration, causal attribution, timing, and committee assessment. The serious-event counts do not determine how many participants met that definition. Since the DLT result is not reported in the registry record, the safety summaries cannot fill that gap.

13. What the Result Does, and Does Not, Mean

The record establishes that this was a Phase I, single-group study of SyB L-1101 in patients with recurrent/relapsed or refractory myelodysplastic syndrome, with 9 participants enrolled. It identifies 1200 mg/day and 1800 mg/day dose groups and describes the study's purpose as evaluating tolerability, DLTs, the maximum tolerated dose, a recommended phase II dose, pharmacokinetics, and antitumor effects. Those are the stated aims, not all reported findings.

The posted safety summaries show serious adverse events in 0 participants among 3 at risk in the 1200 mg/day group and 2 participants among 6 at risk in the 1800 mg/day group. Other adverse events were reported in 3 participants among 3 at risk in the first group and 6 among 6 at risk in the second. The serious-event terms are listed with reported incidences of 16.7%. These figures describe the registry's event reporting; they do not, by themselves, establish comparative risks or identify a dose effect.

The record does not report the primary endpoint result: the count of participants who experienced DLTs. It also does not report the results of the listed hematologic remission and hematologic improvement outcomes, or findings for pharmacokinetics and antitumor effects. A reader therefore cannot use the posted results to determine the DLT frequency, assess the uncertainty around that frequency, or establish which dose was recommended.

In general, an uncontrolled early-phase study can describe events among participants exposed to a treatment and can inform questions for further research. It cannot provide the same controlled comparison as a randomized trial. Even a complete count in each dose group would need to be interpreted in light of the small enrollment, the cohort design, endpoint definitions, observation, and uncertainty. The posted record does not support a conclusion that SyB L-1101 does or does not work, nor does it support medical decisions. It supports a limited description of the study design and posted adverse-event counts, with the central primary endpoint result absent.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between an endpoint being defined and an endpoint being reported. The registry describes a specific DLT outcome, including event criteria and an observation window, but does not report the number of participants who met that definition. Without that result, the main dose-tolerability question cannot be answered from the posted primary outcome data, no matter how clear the endpoint definition is.

It also shows why study structure matters when reading event counts. The record describes a single-group Phase I study, not a randomized comparison. The 1200 mg/day and 1800 mg/day groups are dose cohorts with different reported denominators. Their counts are informative as descriptions of observed safety reporting, but any apparent difference could reflect factors other than dose. Treating the cohorts as treatment and control arms would overstate what the design can establish.

Small participant counts make transparent denominators especially important. The registry reports 3 participants at risk in one group and 6 in the other, alongside the number affected. Counts preserve the actual scale of the evidence and discourage false precision. At the same time, the lack of a reported primary outcome estimate and uncertainty measure limits even descriptive assessment of DLTs.

Finally, multiple outcomes and planning assumptions should not be mistaken for trial findings. The registry lists 4 outcome measures and 0 analyses. The sample-size assumptions are planning illustrations, not proof of observed power or a description of the study's own design. Clear separation of study aims, observed safety summaries, planned calculations, and missing results is essential to sound statistical interpretation.

15. 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 important trial-specific limitation in the registry record is the absence of the primary DLT result. Although the outcome definition and timeframe are described, the record does not report how many participants experienced a DLT. It also does not report the maximum tolerated dose or a recommended dose for phase II studies, despite identifying these as study aims. This prevents direct interpretation of the central dose-finding outcome.

The total enrollment was 9, with 3 participants at risk in the 1200 mg/day group and 6 in the 1800 mg/day group for the adverse-event summaries. Such small cohorts provide limited precision for safety descriptions. The study is single group, with no randomized control, so comparisons between dose cohorts are not controlled comparisons. The registry record does not report an adjusted analysis that might address differences between cohorts.

There is also incomplete reporting of outcomes and analysis methods. The record lists 4 outcome measures and 0 analyses. Results for the two named hematologic secondary outcomes are not reported, and no statistical analysis plan, missing-data approach, or analysis population is reported. The record does not provide a sample-size justification. These omissions limit assessment of how outcomes were selected, analyzed, and interpreted.

The adverse-event summaries do not resolve the missing DLT result. They report serious and other events as separate categories, without participant-level overlap or a mapping to the DLT criteria. Deaths are not reported in the registry record. The primary endpoint timeframe is listed as up to 60 weeks, while its description refers to qualifying events by the final observation in Cycle 2; the relationship between those timing statements is not further specified. The complete administration description for the 1800 mg/day group is also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS) — NCT01700335.
• Registry record last updated 2022-11-21; status last verified 2022-10.
• Results first posted 2016-09-14.
• 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.

19. Record Summary

The registry record describes a completed Phase I, single-group study of SyB L-1101 in patients with recurrent/relapsed or refractory myelodysplastic syndrome. It reports 9 participants enrolled and identifies 1200 mg/day and 1800 mg/day dose groups. Allocation is listed as NA and masking as none. The primary outcome is the number of participants experiencing DLTs, with a timeframe of up to 60 weeks and criteria tied to observation through Cycle 2.

Adverse-event summaries report serious events in 0 of 3 participants at risk in the 1200 mg/day group and 2 of 6 in the 1800 mg/day group. Other adverse events are reported in 3 of 3 and 6 of 6 participants, respectively. The primary DLT result, secondary outcome results, analysis plan, and missing-data methods are not reported in the registry record. The record lists 4 outcome measures and 0 analyses.