A Study to Evaluate the Pharmacokinetics, Safety,and Efficacy of Omacetaxine Given Subcutaneously as a Fixed Dose in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) (Referred to as the SYNSINCT Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Pharmacokinetics, Safety,and Efficacy of Omacetaxine Given Subcutaneously as a Fixed Dose in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) (Referred to as the SYNSINCT Study) (NCT02078960), a na phase 1, phase 2 study. The primary outcome is Number of Participants Who Achieved a Major Response at Any Time During Treatment.

2. Clinical Question

The registry describes a Phase 1/Phase 2 study for people with chronic myeloid leukemia in chronic or accelerated phase after failure of 2 or more tyrosine kinase inhibitor therapies. Its stated purpose was to investigate pharmacokinetics and preliminary safety and efficacy after fixed-dose administration of omacetaxine. The primary endpoint was a count of participants who achieved a major response at any time during treatment, assessed by the Independent Data Monitoring Committee.

For chronic phase disease, major response meant a major cytogenetic response: either complete cytogenetic response, defined as no Ph+ metaphases, or partial cytogenetic response, defined as up to 35% Ph+ metaphases. A complete hematologic response alone did not qualify as a major response for this group. For accelerated phase disease, major response meant a major hematologic response, defined as complete hematologic response or no evidence of leukemia, and/or a major cytogenetic response.

The registry lists 10 enrolled participants, but the numerical result for the primary endpoint is not reported in the registry record. The record therefore does not establish how many participants met the response definition, nor does it provide a treatment-versus-control estimate. The question is descriptive within this single group, rather than a comparative question about differences between treatments.

3. Trial Design

This was an open-label, single-group Phase 1/Phase 2 clinical study of omacetaxine mepesuccinate, administered subcutaneously as a fixed dose. The registry lists allocation as not applicable and masking as none. There was no randomized comparison group. Accordingly, the design can describe outcomes among participants receiving the study intervention, but it cannot directly compare those outcomes with a concurrent control group.

The intended population was people with chronic phase or accelerated phase chronic myeloid leukemia who had failed 2 or more tyrosine kinase inhibitor therapies. The registry lists 10 enrolled participants. The study status is terminated. The listed start date is 2014-10-09, and the primary completion date is 2017-07-06. The reason for termination is not reported in the registry record.

The arm description states that the study would include up to a 7-day screening period and treatment for up to 12 months in the Phase 1 and Phase 2 portions, depending on response and tolerability. It also describes an end-of-treatment follow-up visit approximately 28 days after the last dose. These are descriptions of the study plan; the registry does not report how long each participant was treated.

The stated purpose was to investigate pharmacokinetics and preliminary safety and efficacy following fixed-dose administration. The primary endpoint concerned major response at any time during treatment. Secondary outcomes included response duration, molecular response, progression-free status, survival status, and pharmacokinetic measures. Specific reasons for choosing this design, the intended enrollment rationale, and the statistical plan are 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.

Before assignment: Of the 14 patients screened, 9 patients at 3 centers in the US and 1 patient at a single centre in France met entry criteria and were considered to be eligible for enrollment into the study.

Treatment Period

Reasons for not completing this period:

Follow-up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Enrolled participants

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Enrolled patients

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Achieved a Major Response at Any Time During Treatment, measured over Day 1 up to Month 15 (longest treatment duration).

The primary endpoint is the number of participants who achieved a major response at any time during treatment, with the assessment period described as Day 1 up to Month 15 (longest treatment duration). It is a participant count, not a time-to-event measure or a continuous measurement. The registry says the Independent Data Monitoring Committee assessments are summarized.

The definition differs by disease phase. In chronic phase chronic myeloid leukemia, major response was a major cytogenetic response: complete cytogenetic response with no Ph+ metaphases, or partial cytogenetic response with up to 35% Ph+ metaphases. A complete hematologic response was explicitly not considered a major response for this group. In accelerated phase disease, major response was a major hematologic response, defined as complete hematologic response or no evidence of leukemia, and/or a major cytogenetic response.

In general, a response endpoint can provide a structured way to describe whether participants met specified disease-assessment criteria during a treatment period. A count is straightforward to interpret as the number meeting those criteria, but its meaning depends on a clearly defined assessment, population, and observation period. The registry identifies enrolled participants as the primary population, but does not report the numerical primary result, the number assessed, or details about missing assessments. The result is therefore not reported in the registry record, and the endpoint cannot be quantified from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study, not a randomized treatment comparison. Allocation is listed as not applicable, masking as none, and the model as single group. These are design features, not statistical test results. The record does not report a statistical analysis plan, so the specific methods used to analyze the primary and secondary outcomes are not reported in the registry record.

What does a participant count represent?

The primary measure is a count of participants who achieved a major response at any time during treatment. A count summarizes how many participants met the endpoint definition; it is not itself a comparison between treatment groups. The registry identifies enrolled participants as the population for this outcome. It does not report the number who were evaluable, the number with missing assessments, or whether the analysis population differed from the enrolled population.

In general, a count may be accompanied by a proportion and an uncertainty interval when the relevant denominator and statistical method are specified. Neither a primary count nor a denominator for a calculated proportion is reported in the registry record. No proportion or interval should therefore be inferred from enrollment alone.

Why does the response definition matter?

Endpoint definitions determine which observations count as events. Here, chronic phase major response is defined by cytogenetic criteria, while accelerated phase major response can be defined by hematologic response or cytogenetic response. The definitions are clinically distinct, and the record does not give separate primary outcome results by phase. General interpretation of a combined endpoint should account for such differences in the criteria being applied.

The registry also describes the outcome as a response achieved at any time during treatment. In general, an “at any time” measure depends on when and how often assessments are made, how long participants remain under observation, and how missing assessments are handled. The schedule of response assessments and the approach to missing observations are not reported in the registry record.

What can uncertainty measures tell readers?

In general, a confidence interval expresses uncertainty around an estimated quantity under a stated model and method. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. A p-value, when used, assesses how compatible observed data are with a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect. The registry does not report a primary estimate, confidence interval, p-value, or the method used to calculate them. Statistical precision and evidence against a null hypothesis therefore cannot be evaluated from the registry record.

What does the design allow?

A single-group analysis can describe observed outcomes in the study group. Without a comparator, it cannot produce a randomized between-group treatment contrast. General statistical adjustments cannot replace a missing randomized control when the target is a causal treatment comparison. No adjusted or unadjusted treatment comparison is reported in the registry record.

The sample-size planning assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect set as a stated fraction of an observed effect. Those assumptions are planning illustrations, not the trial's own design or observed power. The study itself is listed as single-group; the registry does not report a sample-size justification or its statistical power plan.

Why can over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular relationship between the mean and variability. Over-dispersion occurs when variability is greater than that assumed by a model. If unaccounted for, it can make uncertainty estimates too small. This is a general statistical consideration, not a method identified for this study. The registry does not report whether a count model, an over-dispersion assessment, or any other specific model was used.

The registry lists 13 outcome measures and no analysis entries. This does not establish which analyses were conducted outside the registry record, nor whether prespecified analyses were changed. Details of the analysis populations, handling of missing data, model assumptions, and multiplicity procedures are not reported in the registry record.

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("Cohort 1", "Cohort 2", "Cohort 3")
n      <- c(2, 4, 4)
events <- c(0, 1, 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  Cohort 1  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Cohort 2  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6
ARM  Cohort 3  4  2  50.0  6.8  93.2  15.0  85.0  14.7  85.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary major-response count and secondary response, survival, progression-free, and pharmacokinetic outcomes. It records no analysis entries. This does not show whether analyses were conducted elsewhere, and the registry does not describe a statistical analysis plan or identify which outcomes were tested inferentially.

When several outcomes are assessed, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently unusual result under a set of null hypotheses. In general, methods such as a prespecified testing hierarchy or adjustment can address that issue. The registry record does not report whether any such strategy was planned or used. No adjusted or unadjusted p-values for the primary outcome are reported.

Missing-data methods are also not reported in the registry record. The entry does not state how participants with incomplete follow-up, unavailable response assessments, or early discontinuation were handled in the primary analysis. The planned treatment duration depended on response and tolerability, but this description does not establish actual exposure or the analysis consequences of stopping treatment.

The primary population is described as enrolled participants, and the record lists 10 enrolled. It does not specify whether the endpoint analysis included all enrolled participants, only those treated, or another defined population. The number with an available primary endpoint assessment is not reported. These gaps prevent evaluation of how missing observations or analysis-population choices might affect the result.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (50.0%), thrombocytopenia (50.0%), stomatitis (50.0%), abscess limb (50.0%), pneumonia (50.0%).

The registry presents serious adverse event and other adverse event entries by cohort, along with death counts. Cohort 1 lists 2 at risk and 2 affected for serious adverse events, 2 at risk and 2 affected for other adverse events, and 2 deaths. Cohort 2 lists 4 at risk and 2 affected for serious adverse events, 4 at risk and 4 affected for other adverse events, and 0 deaths. Cohort 3 lists 4 at risk and 4 affected for serious adverse events, 4 at risk and 4 affected for other adverse events, and 1 death.

The listed serious adverse event terms are neutropenia, thrombocytopenia, stomatitis, abscess limb, pneumonia, and septic shock; each is shown as 50.0%. The denominator and the relationship between these term percentages and the cohort entries are not reported in the registry record. The percentages should therefore be read as registry-listed values, not converted into counts or treated as rates across all enrolled participants.

These entries describe events recorded in the study; they do not establish that omacetaxine caused an event. The registry does not provide additional detail about event timing, severity grading, duration, or attribution. Cohort-level figures should be interpreted in that limited descriptive context.

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

The registry record establishes that a Phase 1/Phase 2, open-label, single-group study was conducted to investigate fixed-dose subcutaneous omacetaxine in chronic or accelerated phase chronic myeloid leukemia after failure of 2 or more tyrosine kinase inhibitor therapies. It defines a primary endpoint based on major response and lists safety, survival, response-duration, molecular-response, and pharmacokinetic outcomes.

However, the record does not report a numerical result for the primary endpoint. It therefore does not show how many enrolled participants achieved a major response, how the result differed between disease phases, or how precise an estimate might be. The endpoint definition explains what would count as a response; it does not provide evidence about the number who responded.

The single-group design also limits interpretation. In general, outcomes observed in one study group do not supply a direct randomized comparison with another treatment. The registry does not support a comparative treatment effect estimate. The study's terminated status is recorded, but the reason for termination is not reported in the registry record, and the status does not by itself explain the clinical outcomes.

The serious adverse event entries and deaths are descriptive registry listings. They do not establish causality, and the record does not provide enough detail to interpret the listed serious event percentages as rates with a clear denominator. The pharmacokinetic outcomes are named, but their numerical results are not included in the registry record for this analysis.

In general, a statistical result is most informative when its estimate, uncertainty, analysis population, and methods are available together. Several of those elements are not reported in the registry record. The appropriate interpretation is therefore limited to the design, definitions, enrollment, and adverse event entries that are recorded; efficacy magnitude, precision, comparative effects, and missing-data sensitivity cannot be determined from this information.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and study design must be considered together. The primary endpoint is a participant count, but “major response” is defined differently for chronic phase and accelerated phase disease. The distinction is important because an overall count can combine outcomes based on different clinical assessment criteria. Without phase-specific primary results, the registry does not show how the endpoint was distributed across those groups.

The single-group design is also central to statistical interpretation. A response count can describe the study group, but a comparator is needed for a direct treatment contrast. Allocation is listed as not applicable, masking as none, and the model as single group. These registry entries prevent interpretation as a randomized comparative trial, regardless of how precisely a within-group outcome might be measured.

The record further demonstrates the difference between an outcome being defined and an outcome being reported. The primary endpoint definition is detailed, yet its numerical result is not reported in the registry record. Without that result and its uncertainty, readers cannot assess the observed response frequency or precision. The same caution applies to named pharmacokinetic outcomes whose numerical results are not present in the available record.

Finally, the cohort adverse event entries show why denominator clarity matters. Percentages listed for serious adverse event terms cannot be interpreted as population rates without knowing the relevant denominator and analysis rules. A registry can supply important design and endpoint context, but missing results and methods constrain the conclusions that can be drawn from it.

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 primary limitation is that the registry record does not report a numerical result for the primary major-response endpoint. It also does not report a primary estimate, confidence interval, p-value, or a phase-specific primary result. The endpoint definition is available, but the observed outcome and its statistical precision are not.

The study is single-group and has no randomized comparator. As a result, the record cannot provide a direct randomized comparison with another treatment. The study is open label, with masking listed as none. The registry does not report the reason for termination, the number who received treatment, actual treatment duration, or the number assessed for the primary endpoint.

Important analysis details are not reported in the registry record, including the statistical analysis plan, analysis population beyond the label of enrolled participants, handling of missing assessments, and multiplicity procedures. The record lists 13 outcome measures but no analysis entries. It does not indicate which analyses were performed or whether their methods were prespecified.

Interpretation of safety entries is limited because the registry does not report the denominator underlying the listed serious adverse event term percentages in the information available. Additional detail on event timing, grading, and attribution is not provided. The listed death counts do not, on their own, establish cause.

These limitations mean that the registry information supports description of the study design, outcome definitions, enrollment, and listed adverse event entries, but not a quantitative assessment of efficacy or comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics, Safety,and Efficacy of Omacetaxine Given Subcutaneously as a Fixed Dose in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) (Referred to as the SYNSINCT Study) — NCT02078960.
• Registry record last updated 2021-11-09; status last verified 2021-11.
• Results first posted 2019-01-14.
• 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

NCT02078960 is a terminated, open-label, single-group Phase 1/Phase 2 study of fixed-dose subcutaneous omacetaxine mepesuccinate in participants with chronic or accelerated phase chronic myeloid leukemia who had failed 2 or more tyrosine kinase inhibitor therapies. The registry lists 10 enrolled participants, a start date of 2014-10-09, and a primary completion date of 2017-07-06.

The primary outcome was the number of participants who achieved a phase-specific major response at any time during treatment. The registry record does not report the numerical primary outcome result. The record lists secondary response, survival, progression-free, and pharmacokinetic outcomes, as well as adverse event entries by cohort. It does not report the statistical analysis plan, missing-data methods, or reason for termination.