Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (NCT02882321), a non-randomized phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) Defined as the Highest Dose Studied for Which the Observed Incidence of Dose Limiting Toxicities (DLT) is Less Than 33%.

2. Clinical Question

The study also listed response, duration of response, progression-free survival, and overall survival as secondary outcomes. These outcomes could describe antitumor activity and time-to-event experience, but no outcome estimates or analyses for them are reported in the registry record. The stated trial rationale was to examine side effects and identify a dose for a drug intended to block enzymes needed for cancer-cell growth. That rationale is not evidence of clinical benefit. The listed design and posted results support a description of the dose-finding question and safety counts, not a comparative conclusion about treatment effects.

3. Trial Design

NCT02882321 is a phase 1 study titled “Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia.” The registry identifies M.D. Anderson Cancer Center as sponsor. The study is marked non-randomized, unmasked, and parallel, with enrollment of 17. Its status is terminated. The reason for termination is not reported in the registry record.

The four listed cohorts received IACS-010759 at different starting doses: 0.5 mg, 1 mg, 2 mg, and 2.5 mg. The cohort descriptions specify oral once-daily dosing on days 1-7 during induction. For the 2 mg and 2.5 mg cohorts, maintenance is also described: dosing on days 8 and 15 of course 1, then days 1, 8, and 15 of subsequent courses. The provided description for the 2.5 mg cohort ends mid-word after “cours”; further details are not reported in the registry record. The descriptions do not give equivalent maintenance schedules for the first two cohorts.

The study began on 2016-09-29 and has a primary completion date of 2022-04-15. These dates describe the registry timeline, not the availability of a complete results analysis. Although the primary outcome concerns maximum tolerated dose, the record does not describe dose-assignment rules, escalation or de-escalation procedures, cohort-size rules, or a statistical analysis plan. Those design details should not be inferred from the presence of multiple starting-dose cohorts.

Because the study was non-randomized and its listed groups are treatment cohorts, cohort differences may reflect more than dose. The registry description does not establish that participants in different cohorts were comparable or that allocation was governed by a random mechanism. The design therefore addresses an early-phase dose-finding question rather than a controlled comparison of IACS-010759 with another treatment.

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 Maximum Tolerated Dose (MTD) Defined as the Highest Dose Studied for Which the Observed Incidence of Dose Limiting Toxicities (DLT) is Less Than 33%, measured over Up to 28 days.

The primary endpoint is maximum tolerated dose, expressed in milligrams. The registry defines it as the highest dose studied for which the observed incidence of dose-limiting toxicities is less than 33%. The stated assessment window is up to 28 days, and toxicities were to be assessed according to National Cancer Institute Common Toxicity Criteria version 4.03.

This endpoint is used in early-phase dose-finding because it links observed toxicity during a specified period to the selection of a dose for further study. It is a safety-based decision criterion, not an estimate of tumor response or survival benefit. The phrase “highest dose studied” also matters: the endpoint concerns the doses actually evaluated under the study’s procedures, not every possible dose.

The registry record does not report the number or proportion of participants with dose-limiting toxicities by dose, the dose ultimately selected, or the maximum tolerated dose result. It also does not report the operational definition of a dose-limiting toxicity beyond the reference to the toxicity criteria. As a result, the endpoint’s definition can be described, but its observed value and the evidence supporting any dose decision cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the dose-finding endpoint means. The primary outcome is a threshold-based dose-selection measure. In general, maximum tolerated dose is intended to identify a dose that satisfies a prespecified toxicity criterion within an observation period. Here, the registry defines it as the highest dose studied with an observed dose-limiting toxicity incidence below 33%, assessed up to 28 days. This is a rule for interpreting observed toxicity, not a guarantee that the selected dose is safe for every participant or that it is effective.

The endpoint depends on how dose-limiting toxicity is defined, which participants contribute to the assessment, and how observations are handled when follow-up is incomplete. The record names National Cancer Institute Common Toxicity Criteria version 4.03, but does not report the detailed dose-limiting toxicity definition, analysis population, or missing-observation rules. The observed toxicity counts used for the endpoint and the selected dose are also not reported in the registry record.

How to read cohort counts. A count of participants affected is a descriptive summary, and its meaning depends on the number of participants at risk and the event definition. In this study, cohort sizes are small, so each participant’s experience contributes materially to the group summary. Such counts can flag events recorded during the study, but they do not by themselves establish causality, compare treatment doses fairly, or quantify uncertainty. General statistical principle: estimates based on small groups tend to be less precise than estimates based on larger groups, and uncertainty intervals help convey that imprecision. No confidence intervals for the adverse-event counts are reported in the registry record.

The serious adverse-event counts and the other adverse-event counts are separate summaries. They should not be merged or treated as if they measure the same severity category. The registry also lists serious adverse-event terms with percentages, but does not make the denominator and grouping basis explicit in the summary. A percentage without a clearly described denominator is difficult to interpret as a participant-level risk or a dose-specific rate.

Why randomization matters. General statistical principle: random allocation helps balance measured and unmeasured participant characteristics across groups, on average, making a direct comparison more credible. This study is non-randomized, and its treatment cohorts are not a like-for-like control comparison. Cohort contrasts may be affected by differences in who entered each cohort, treatment timing, or other factors; the registry record does not provide enough information to adjust for such differences. Therefore, a difference in observed counts across cohorts would not, by itself, demonstrate that dose caused the difference.

The registry describes a parallel model and four treatment cohorts. Parallel groups can be followed as distinct groups, but the label does not establish random assignment or comparability. The record does not specify the allocation process, cohort entry criteria, or whether participants could move between cohorts. It is not appropriate to infer those procedures from the design labels alone.

Secondary outcomes and analysis. The listed secondary outcomes are participants with a response, duration of response, progression-free survival, and overall survival. General statistical principle: response is typically summarized as a categorical outcome, while duration and survival outcomes involve time and may require methods that account for censoring when event times are not fully observed. The registry record does not provide outcome definitions, time origin, censoring rules, estimates, or analysis methods for these outcomes. Thus, those general methods cannot be attributed to this study’s actual analysis.

The record lists five outcome measures and zero analyses. This indicates that the registry results summary does not include statistical analyses for the listed outcomes. It does not establish that no analyses were conducted outside the registry. No p-values, effect estimates, confidence intervals, or model results for efficacy outcomes are reported in the registry record.

Uncertainty and sample size. General statistical principle: a confidence interval describes a range of values compatible with the data and the analysis assumptions; it is not a guarantee that the true value lies in that range. No confidence interval is reported for the primary endpoint or the secondary outcomes, so the precision of those estimates cannot be evaluated from the record. The enrollment of 17 is a study-level count, not an estimate of statistical power.

Sample-size calculations are planning tools and depend on assumptions about the outcome, the effect to detect, the significance level, allocation, and statistical method. They are not observed evidence about treatment effects. The registry record does not report a study-specific sample-size justification or analysis plan. It also does not provide the observed effect estimates needed to interpret a planning illustration as a trial result. No sample-size illustration should be read as observed power or as evidence that a clinical effect was demonstrated.

Multiplicity refers, in general, to the increased chance of at least one misleading positive finding when several hypotheses are tested. The study lists multiple outcomes, but no testing hierarchy, multiplicity adjustment, or inferential analysis is reported in the registry record. Without that information, it is not possible to determine how any outcome testing was prioritized or interpreted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary dose-finding outcome and secondary outcomes covering response, duration of response, progression-free survival, and overall survival. It does not report an analysis plan describing a testing hierarchy, multiplicity adjustment, or confirmatory role for any secondary outcome. General statistical principle: when several outcomes are tested, the chance of a chance-positive result can rise unless the analysis plan accounts for that multiplicity. No adjustment method or associated inference is reported in the registry record, so the handling of multiple outcomes cannot be evaluated.

Missing-data procedures are not reported in the registry record. This includes rules for incomplete toxicity observation, missed assessments, withdrawal, and incomplete follow-up for response or survival. Those details matter because the endpoint depends on toxicity observed during up to 28 days, while response duration and survival outcomes depend on follow-up over time. The record does not state how participants with incomplete observations were included or excluded.

Analysis populations are also not reported. The registry does not specify which participants contributed to each endpoint, whether all enrolled participants were analyzed, or whether eligibility for an endpoint required receiving treatment or completing an assessment. Accordingly, the cohort adverse-event counts can be described as posted, but the population definitions behind other outcomes cannot be reconstructed.

The registry records 17 participants enrolled and five outcome measures, but zero analyses. It does not report a study-specific sample-size justification, interim analysis procedures, or a statistical analysis plan. The absence of these details in the registry record does not establish what investigators may have done outside the record; it limits what can be assessed from the posted information.

11. 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: infection (66.7%), neurology (33.3%), neuropathy (33.3%), pleural effusion (33.3%), hemorrhage/bleeding-other (specify) (28.6%).

The safety summary separates serious adverse events from other adverse events and reports the number at risk and affected within each treatment cohort. For serious adverse events, the affected counts are 3 of 4 in Cohort 1, 2 of 3 in Cohort 2, 3 of 3 in Cohort 3, and 4 of 7 in Cohort 4. For other adverse events, the affected counts are 4 of 4, 3 of 3, 3 of 3, and 7 of 7, respectively. These counts should be read within their cohort sizes rather than as evidence of a dose trend.

The registry lists serious adverse-event terms and percentages, including Infection at 66.7% and Neurology and Neuropathy at 33.3%. The summary does not specify the denominator and detailed grouping basis for these percentages. It also reports deaths by cohort as 0, 1, 1, and 3. The registry summary does not establish whether those deaths were caused by treatment, so they should not be interpreted as treatment-related deaths.

These safety summaries are descriptive. The registry record does not report confidence intervals, a comparative safety analysis, or the dose-limiting toxicity results needed to determine the primary endpoint. Adverse-event counts should not be treated as proof of causation or as a substitute for the protocol-defined endpoint.

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

The posted information establishes that NCT02882321 was a phase 1, non-randomized study of IACS-010759 in participants with recurrent or refractory acute myeloid leukemia. It records four treatment cohorts with different starting doses and a primary objective focused on maximum tolerated dose. It also records adverse-event counts and lists response and survival outcomes as secondary measures.

The information does not establish which dose met the maximum tolerated dose definition. The observed dose-limiting toxicity results and the selected dose are not reported in the registry record. Nor are response, duration-of-response, progression-free-survival, or overall-survival estimates reported. Consequently, the posted results do not allow estimation of antitumor activity, comparison with another treatment, or assessment of the precision of any efficacy estimate.

The safety counts show that adverse events were recorded among participants in each cohort, but the counts alone do not establish that IACS-010759 caused those events. The cohort groups were not randomized, are small, and are not a like-for-like control comparison. The record does not report an adjusted comparison or uncertainty intervals. It is therefore not possible to attribute differences among cohort counts to dose or draw a causal conclusion from those differences.

The registry status is terminated, but the reason for termination is not reported in the registry record. That status alone does not explain whether the study stopped for safety, feasibility, administrative, or other reasons. Likewise, the stated biological rationale for the drug is a rationale, not evidence that the treatment achieved a clinical outcome.

The most defensible reading is limited: the record describes the study design and the safety information that was posted, while leaving the primary dose-finding result and secondary outcome analyses unavailable. It does not support a conclusion that the drug works or does not work, or a conclusion about its comparative safety or benefit.

13. Why This Trial Matters Statistically

This trial illustrates why early-phase studies are interpreted differently from randomized treatment comparisons. The central question was dose-finding, with maximum tolerated dose defined through an observed toxicity threshold over up to 28 days. That endpoint is distinct from response or survival, and a dose-finding result would not, on its own, establish clinical benefit.

The four treatment cohorts make the registry’s non-randomized design important to interpretation. Cohort-level safety counts can describe what was recorded, but differences between these groups do not isolate a dose effect when allocation is not randomized and comparability is not established. The small cohort counts also make it essential to attend to uncertainty rather than treating a count or percentage as a stable estimate.

The record further demonstrates that a list of planned outcomes is not equivalent to reported results. Response and survival outcomes are named, but no analyses for them are posted. Without estimates, definitions, analysis populations, and follow-up rules, readers cannot assess those outcomes or their precision. Similarly, a primary endpoint definition is not a primary endpoint finding: the registry’s criterion is stated, but the resulting dose is absent.

Statistically, the useful distinction is between what the record describes and what it supports. The design, cohort starting doses, endpoint definition, and adverse-event counts are descriptive details. A causal dose comparison, a dose recommendation, and an efficacy conclusion would require results and methods that are not reported in the registry record. Recognizing that boundary prevents a descriptive phase 1 record from being read as comparative evidence.

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 main limitation is that the registry record does not report the primary endpoint result. It defines maximum tolerated dose but does not provide dose-limiting toxicity counts by dose or state the maximum tolerated dose identified. The secondary outcomes are listed without results or analyses. This prevents evaluation of both the dose-finding objective and the stated response and survival outcomes.

The study is non-randomized, and the listed groups are treatment cohorts rather than a like-for-like control comparison. The record does not describe enough about cohort assignment or participant characteristics to assess comparability. Differences among cohort counts therefore cannot be interpreted as causal dose effects.

Enrollment was 17, with small participant counts in each cohort. Estimates based on such groups can be imprecise, yet confidence intervals and other uncertainty measures are not reported. The registry also does not report analysis populations, missing-data rules, detailed dose-limiting toxicity criteria, multiplicity procedures, a study-specific sample-size justification, or an analysis plan. These omissions limit the reproducibility and statistical assessment of the reported outcomes.

The serious adverse-event percentages are listed without an explicit denominator or detailed grouping basis in the summary. The cohort death counts are also not accompanied by information establishing treatment causality. Finally, the record states that the study was terminated but does not report why. These limitations constrain interpretation of the safety information and do not permit a conclusion about the reason for study termination.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia — NCT02882321.
• Registry record last updated 2023-06-15; status last verified 2023-06.
• Results first posted 2023-06-15.
• 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.

18. Record Summary

NCT02882321 is a phase 1, non-randomized, unmasked, parallel study of oxidative phosphorylation inhibitor IACS-010759 in recurrent or refractory acute myeloid leukemia. The sponsor is M.D. Anderson Cancer Center. The registry records enrollment of 17, a start date of 2016-09-29, primary completion on 2022-04-15, and terminated status.

Four treatment cohorts are listed, with starting doses of 0.5 mg, 1 mg, 2 mg, and 2.5 mg. The primary outcome is maximum tolerated dose, defined by a dose-limiting toxicity incidence below 33% over up to 28 days. The record does not report the primary endpoint result. Response, duration of response, progression-free survival, and overall survival are listed as secondary outcomes, with no analyses reported.

Adverse-event counts are posted by cohort, but the record does not establish treatment causality or provide a like-for-like control comparison. The reason for termination and the study’s detailed statistical plan are not reported in the registry record.