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 BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients With AML in Complete Remission With High Risk to Relapse (NCT01690624), a non-randomized phase 1 study. The primary outcome is Determination of the Maximum Tolerated Dose (MTD) of BI 836858.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01690624 |
| Phase | Phase 1 |
| Condition | Leukemia, Myeloid, Acute |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
The trial included patients with acute myeloid leukemia (AML) who had refractory or relapsed disease, as well as patients in complete remission with high risk to relapse. The registry record describes eligibility for these groups but does not report further eligibility criteria in the information available for this analysis. The recorded enrollment is 30.
Intervention
Participants received BI 836858 as monotherapy at escalating dose levels. The relapsed or refractory AML groups received 10 mg, 20 mg, or 40 mg intravenously on day 1 and day 8 of 14-day cycles. The complete-remission group received 40 mg intravenously on day 1 of the first three cycles, with less frequent administration described thereafter; the later schedule is incomplete in the registry record.
Comparator
There was no randomized control group. The dose groups were sequential, non-randomized cohorts, so comparisons between them are not like-for-like control comparisons. Differences between groups cannot be separated from differences in the patients enrolled, the disease setting, or the dose schedule using the information reported in the registry record.
Primary question
The primary objective was to determine the maximum tolerated dose (MTD) of BI 836858, measured in milligrams. The registry record says the trial was discontinued before reaching this endpoint. It therefore does not report an MTD determination. The broader stated aim was to examine safety and tolerability across escalating doses; the reported serious adverse event figures describe safety observations but do not, on their own, establish a dose as tolerable or identify an MTD.
3. Trial Design
This was a phase I, open-label, non-randomized trial using a sequential cohort dose-escalation model. The registry record identifies Boehringer Ingelheim as the sponsor and lists the trial status as completed. It records enrollment of 30. The trial started on 2012-09-13, and primary completion is recorded as 2018-05-21.
The treatment was BI 836858 given as an intravenous infusion. The relapsed or refractory AML cohorts received 10 mg, 20 mg, or 40 mg on day 1 and day 8 of 14-day cycles. A separate 40 mg cohort was for patients with AML in complete remission and high risk to relapse; its schedule began with infusions on day 1 of the first three cycles and then changed to infusions every second cycle. The description of that later schedule is cut off in the registry record, so the full administration schedule is not reported there.
Open-label means that masking was not used, as also indicated by the record. Sequential dose escalation means the cohorts were arranged by dose rather than assigned through randomization. This design fits an exploratory dose-finding question, but it does not create a randomized comparison of dose levels or disease settings. The registry record does not report the rules governing dose escalation, the criteria for stopping escalation, or a statistical analysis plan. It also does not report a sample-size justification.
The record lists secondary outcomes spanning response categories, progression-free survival, time to treatment failure, and pharmacokinetic measures. It gives 18 outcome measures and records 0 analyses. These listings indicate the breadth of planned outcome assessment, not evidence that each outcome was analyzed or that results were reported.
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: This study initially enrolled patients diagnosed with refractory or relapsed AML who had failed at least 1 prior line of therapy and was later amended to include patients with AML who were in CR with a high risk to relapse.
Overall Study
| Stage | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) |
|---|---|---|---|---|
| STARTED | 12 | 8 | 7 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 12 | 8 | 7 | 3 |
Reasons for not completing this period:
| Reason | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) |
|---|---|---|---|---|
| PD based on IWG criteria or clinical PD | 8 | 5 | 2 | 0 |
| Adverse event (other than DLT) | 3 | 1 | 1 | 1 |
| Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Sponsor is ending trial | 0 | 0 | 0 | 1 |
| Physician Decision | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Lack of Efficacy | 1 | 1 | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: MTD evaluable set (non-replaced patients) defined as patients who completed the first two treatment cycles.
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: Treated Set (TS): TS included patients treated with at least 1 dose of BI 836858.
| Characteristic | Unit | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 12 | 8 | 7 | 3 | 30 | |
| Age, Continuous | Years | 61.0 (SD 12.4) | 60.8 (SD 7.6) | 72.3 (SD 6.7) | 49.0 (SD 17.5) | 62.4 (SD 12.1) |
| Sex: Female, Male: Female | Participants | 6 | 2 | 4 | 1 | 13 |
| Sex: Female, Male: Male | Participants | 6 | 6 | 3 | 2 | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 5 | 7 | 3 | 16 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 11 | 3 | 0 | 0 | 14 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 2 | 0 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 12 | 6 | 6 | 3 | 27 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Determination of the Maximum Tolerated Dose (MTD) of BI 836858, measured over From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Milligram (mg) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was determination of the maximum tolerated dose of BI 836858, expressed in milligrams. The registry record defines the MTD-evaluable set as non-replaced patients who completed the first two treatment cycles. Its stated endpoint timeframe runs from the first administration to the start of the fifth administration, excluding the day of the fifth administration, up to 28 days.
General: In dose-escalation research, an MTD is a dose-finding quantity used to characterize tolerability under specified treatment and assessment conditions. Its interpretation depends on the protocol’s definitions of dose-limiting toxicity, the observation window, escalation and stopping rules, and the population included in the assessment. Those rules are not reported in the registry record, so the exact decision process intended for this trial cannot be reconstructed from the endpoint description alone.
The record explicitly states that the trial was discontinued before reaching the primary endpoint. Consequently, no MTD value is reported, and the endpoint cannot be interpreted as an estimate with known precision. The timeframe and evaluable-set definition describe how the endpoint was intended to be assessed; they do not mean that the endpoint was completed. The registry record does not provide a reason for discontinuation or further details on endpoint assessment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the trial did not reach its primary endpoint. Although the primary objective was to determine the MTD, the registry record states that the trial was discontinued before that determination. There is therefore no reported MTD estimate to interpret, and the record does not establish which dose, if any, met the intended criteria.
The design was non-randomized and sequential. The listed dose groups should not be read as treatment and control arms in a comparative trial. In particular, the 40 mg group in patients with AML in complete remission is a different clinical population from the 40 mg relapsed or refractory AML group, and its administration schedule also differs. Any apparent variation in outcomes across these cohorts could reflect those differences as well as treatment dose. The registry record does not report an analysis that adjusts for such differences.
The safety information reports counts of participants affected by serious and other adverse events in each cohort, along with serious adverse event terms and percentages. These figures describe the posted safety data at the group level. They are not a randomized comparison, and the record does not provide exposure-adjusted rates, event timing, attribution to treatment, or a statistical comparison between cohorts. The serious event term “Death” is also listed among the terms with percentages; it should not be conflated with the separate group-level death counts without definitions of the coding and denominators.
The registry includes secondary outcomes such as best overall response, progression-free survival, time to treatment failure, and pharmacokinetic measures. However, it records 0 analyses and does not provide numerical results for these outcomes in the registry record used for this interpretation. Their inclusion in the outcome list does not show what was observed. No conclusion about response, survival, or drug concentration can be drawn from outcome names alone.
Planning illustrations based on observed effects, where present in the statistical material, are not trial results or evidence of observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Because this trial was non-randomized and does not present a like-for-like control comparison, such hypothetical calculations should not be read as a design rationale or as a causal comparison between its cohorts. The sample-size justification and the trial’s own statistical plan are not reported in the registry record.
9. Statistical Methods Explained
What does non-randomized, sequential allocation mean?
General: Randomization assigns participants to treatment groups using a chance process, helping make groups comparable on average. In a sequential dose-escalation design, cohorts receive dose levels in an ordered progression instead. The registry record identifies this trial as non-randomized and sequential. Its dose cohorts therefore do not function as randomized control groups. Comparisons between their observed data are descriptive unless a suitable analysis and assumptions support a stronger interpretation; no such comparative analysis is reported in the registry record.
The record lists 10 mg, 20 mg, and 40 mg cohorts for relapsed or refractory AML, and a separate 40 mg cohort for AML in complete remission with high risk to relapse. The disease setting and dosing schedule differ across the cohorts. This makes direct interpretation of cohort differences especially limited: dose, disease context, and schedule are not varied independently in the available information.
What is an MTD endpoint intended to capture?
General: Dose-finding studies commonly seek a dose that meets protocol-defined tolerability criteria during a specified assessment period. The MTD is not simply the largest dose listed in a trial. It depends on what toxicities count, how they are graded, how long participants are observed, and the rules for escalation and stopping. These protocol details are not reported in the registry record. The record does define an MTD-evaluable set as non-replaced patients who completed the first two treatment cycles and specifies a timeframe tied to administrations and up to 28 days. Those definitions explain the intended assessment framework, but the trial’s stated discontinuation before the endpoint means no MTD determination is available.
A dose-escalation objective is different from a test of efficacy. The primary endpoint is a dose in milligrams, rather than a response or survival measure. Response, progression-free survival, time to treatment failure, and pharmacokinetic outcomes appear in the secondary outcome list, but the registry record does not provide numerical findings for them in the registry record.
How should confidence intervals and statistical significance be understood?
General: A confidence interval describes the range of estimates that are compatible with the data under a specified statistical method. A narrow interval indicates greater precision than a wide interval, while an interval that spans a broad range signals substantial uncertainty. A p-value, when reported, measures how unusual data would be under a specified null model; it does not measure the probability that a treatment works or that the null model is true. No confidence intervals or p-values for the primary endpoint or secondary clinical outcomes are reported in the registry record used for this analysis. It is therefore not possible to assess their statistical precision or significance from the outcome listings.
Why does over-dispersion matter?
General: Over-dispersion occurs when observed variation is greater than a statistical model expects. It can make standard errors too small and confidence intervals too narrow if the model assumes less variability than the data contain. Appropriate methods may account for over-dispersion when the outcome and study design call for it. The registry record does not report the statistical models or variance assumptions used for the listed outcomes, so whether over-dispersion was considered is not reported in the registry record.
What do planning illustrations say?
General: Sample-size planning calculations describe how much information a hypothetical study might need under stated assumptions. They do not establish that a trial had a particular probability of detecting an effect after the fact. The planning illustration assumptions described for this analysis use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. Time-to-event illustrations refer to a total number of events, while other illustrations refer to participants per arm for 80% power or another stated power level.
Those calculations are planning illustrations, not observed power and not evidence about the trial’s actual design. The registry record identifies a non-randomized, sequential trial rather than a two-arm randomized comparison. It does not report a sample-size justification or say that the illustration assumptions governed enrollment. The illustrated sample sizes should therefore be understood only in relation to their stated hypothetical assumptions. They do not supply a missing MTD estimate or establish the performance of this trial’s dose-escalation process.
What can be inferred from reported outcome counts?
General: Counts describe how many participants in a defined group experienced an event, but their meaning depends on the group definition, observation period, event definition, and completeness of follow-up. A count is not a rate unless its denominator and time basis are clear. Likewise, a percentage is interpretable only when its denominator and calculation are defined. The registry record provides group-level safety counts and a list of serious event terms with percentages, but the denominator details and exposure-adjusted analyses are not reported in the registry record. The groups also do not form randomized comparisons. The figures can be described as posted, but they do not support a causal comparison between dose levels.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 18 outcome measures, including best overall response categories, progression-free survival, time to treatment failure, and pharmacokinetic outcomes. It records 0 analyses. This is important context: a list of outcomes is not the same as a set of reported estimates, and it does not indicate which outcomes were tested or how their results were handled.
When a study assesses several outcomes or makes several statistical comparisons, the chance of at least one apparently notable result can increase if each is treated as a separate test. General: Multiplicity methods, such as defining a primary comparison in advance or adjusting inference across tests, can address this issue. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or details of any statistical testing. Whether multiplicity was addressed is therefore not reported in the registry record.
The record defines the MTD-evaluable set as non-replaced patients who completed the first two treatment cycles. It does not provide corresponding analysis-population definitions for the secondary outcomes in the information. Details about missing observations, censoring, withdrawal, imputation, and handling of incomplete follow-up are not reported in the registry record. These omissions limit assessment of how the listed outcomes would have been analyzed and how complete the data were.
For the primary endpoint, the documented discontinuation before MTD determination is more consequential than a missing numerical estimate alone: the stated endpoint was not reached. The registry record does not explain how the discontinuation affected the evaluable set or whether any interim dose-finding decision was made. Such details are not reported in the registry record.
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 |
|---|---|---|---|
| BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | 9 | 12 | 75.0% |
| BI 836858 20 mg (Patients With Relapsed\Refractory AML) | 8 | 8 | 100.0% |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | 6 | 7 | 85.7% |
| BI 836858 40 mg (Patients With AML in CR) | 1 | 3 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | 2 of 12 |
| BI 836858 20 mg (Patients With Relapsed\Refractory AML) | 4 of 8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | 2 of 7 |
| BI 836858 40 mg (Patients With AML in CR) | 0 of 3 |
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 |
|---|---|
| BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | 12 of 12 |
| BI 836858 20 mg (Patients With Relapsed\Refractory AML) | 8 of 8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | 7 of 7 |
| BI 836858 40 mg (Patients With AML in CR) | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 3 of 12 | 3 of 8 | 2 of 7 | 0 of 3 |
| Sepsis | Infections and infestations | 1 of 12 | 3 of 8 | 0 of 7 | 0 of 3 |
| Death | General disorders | 0 of 12 | 2 of 8 | 1 of 7 | 0 of 3 |
| Pyrexia | General disorders | 1 of 12 | 2 of 8 | 0 of 7 | 0 of 3 |
| Delirium | Psychiatric disorders | 1 of 12 | 1 of 8 | 1 of 7 | 0 of 3 |
| Atrial fibrillation | Cardiac disorders | 2 of 12 | 0 of 8 | 0 of 7 | 0 of 3 |
| Pneumonia | Infections and infestations | 1 of 12 | 1 of 8 | 0 of 7 | 0 of 3 |
| Infusion related reaction | Injury, poisoning and procedural complications | 1 of 12 | 1 of 8 | 0 of 7 | 0 of 3 |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 12 | 0 of 8 | 0 of 7 | 0 of 3 |
| Haemorrhage intracranial | Nervous system disorders | 1 of 12 | 0 of 8 | 1 of 7 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 12 | 3 of 8 | 1 of 7 | 2 of 3 |
| Anaemia | Blood and lymphatic system disorders | 4 of 12 | 3 of 8 | 3 of 7 | 3 of 3 |
| Platelet count decreased | Investigations | 3 of 12 | 2 of 8 | 3 of 7 | 2 of 3 |
| Infusion related reaction | Injury, poisoning and procedural complications | 5 of 12 | 2 of 8 | 2 of 7 | 0 of 3 |
| White blood cell count decreased | Investigations | 3 of 12 | 2 of 8 | 2 of 7 | 2 of 3 |
| Hypokalaemia | Metabolism and nutrition disorders | 2 of 12 | 4 of 8 | 1 of 7 | 1 of 3 |
| Constipation | Gastrointestinal disorders | 3 of 12 | 1 of 8 | 3 of 7 | 0 of 3 |
| Fatigue | General disorders | 4 of 12 | 1 of 8 | 0 of 7 | 2 of 3 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 12 | 3 of 8 | 1 of 7 | 0 of 3 |
| Diarrhoea | Gastrointestinal disorders | 3 of 12 | 1 of 8 | 1 of 7 | 1 of 3 |
Serious events with the highest arm-level rate: febrile neutropenia (37.5%), sepsis (37.5%), cytomegalovirus infection (33.3%), death (25.0%), pyrexia (25.0%).
The registry reports serious adverse event counts by cohort. In the 10 mg relapsed or refractory AML group, 9 participants were affected among 12 at risk. In the 20 mg relapsed or refractory AML group, 8 were affected among 8 at risk. In the 40 mg relapsed or refractory AML group, 6 were affected among 7 at risk. In the 40 mg AML in complete remission group, 1 was affected among 3 at risk. These are group-specific counts, not results from randomized comparisons.
The other adverse event counts are 12 among 12 at risk in the 10 mg group, 8 among 8 in the 20 mg group, 7 among 7 in the 40 mg relapsed or refractory group, and 3 among 3 in the complete-remission group. The record separately lists deaths as 2, 4, 2, and 0 for these respective groups. The serious event terms with listed percentages include febrile neutropenia and sepsis at 37.5% each, cytomegalovirus infection at 33.3%, and death, pyrexia, and acute kidney injury at 25.0% each.
The registry record does not report the percentage denominators, exposure time, event timing, or treatment attribution for these terms in the information used. Counts and percentages should therefore be read as descriptions of the posted safety data, not as dose-specific risks or proof that BI 836858 caused an event. The group differences cannot establish a dose-response relationship because allocation was non-randomized and the cohorts are not like-for-like comparisons.
12. What the Result Does, and Does Not, Mean
The record documents a phase I investigation of escalating BI 836858 doses in two AML settings and reports safety observations by cohort. Its primary objective was to determine the MTD, but the trial was discontinued before reaching that endpoint. The record therefore does not supply the dose-finding result that would answer the primary question.
The reported adverse event counts give a descriptive account of affected participants in the listed groups. They do not establish that one dose was safer than another. The cohorts were non-randomized, and the complete-remission group differed from the relapsed or refractory groups in both population and schedule. No adjusted or randomized comparison is reported in the registry record. Similarly, the secondary outcome names do not establish clinical benefit or harm: the record lists outcomes but records 0 analyses, and numerical results for those outcomes are not included in the registry record used.
General: Statistical interpretation depends on both the estimate and its uncertainty, as well as the design that produced it. A count without a defined observation period or a comparative design cannot answer a causal question by itself. A planned endpoint that was not reached is not equivalent to a negative finding; it is an unavailable result for that endpoint. In this trial, the absence of an MTD determination should not be converted into a claim that no dose was tolerable or that a particular dose was appropriate.
Any sample-size calculations based on observed effects are hypothetical planning exercises under their stated assumptions. They are not observed power and do not replace the missing dose-finding result. Overall, the registry record supports description of the trial’s design, intended endpoint, discontinuation before that endpoint, and posted safety counts. It does not support a causal efficacy conclusion, an MTD claim, or a definitive comparison of safety across cohorts.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint and design must be read together. A dose-escalation study can be organized to estimate tolerability at escalating doses, but the intended conclusion depends on reaching the endpoint under defined decision rules. Here, the registry record says that the study was discontinued before determining the MTD. The primary dose-finding question consequently remains unanswered in the posted record.
The example also shows why cohort labels should not be mistaken for comparative treatment arms. Non-randomized sequential cohorts can be useful for describing observations as dose levels change, but patients in separate cohorts may differ for reasons beyond dose. In this record, one cohort is explicitly for AML in complete remission with high risk to relapse, whereas the other cohorts are for relapsed or refractory AML. The schedule is also not identical. Those features prevent a straightforward interpretation of differences as dose effects.
There is a separate distinction between having outcomes listed and having analyses reported. The record includes response, survival, treatment-failure, and pharmacokinetic outcomes but records 0 analyses. This distinction matters to readers assessing how much evidence a registry entry contains: outcome definitions communicate what was intended for assessment, while numerical analyses are needed to evaluate what was observed and with what precision.
Finally, safety counts are informative descriptions but are not self-interpreting. Their meaning depends on denominators, observation time, definitions, and attribution. The registry record does not report all of these details in the registry record. Reading the counts with the design and endpoint status in view helps avoid treating descriptive cohort data as a causal comparison or a completed dose-finding result.
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 most direct limitation is that the primary endpoint was not reached. The registry record says the trial was discontinued before determining the MTD, but does not report why it was discontinued, whether a dose-escalation decision had been made, or how discontinuation affected endpoint assessment. As a result, the intended dose-finding conclusion is unavailable.
The allocation was non-randomized and sequential, with no like-for-like control comparison. The clinical settings differed between cohorts, and the complete-remission group had a distinct schedule. These design features limit comparisons of safety or other outcomes by dose. The registry record does not describe statistical adjustment for differences between cohorts.
The available record also leaves important analytic details unreported. The dose-escalation rules, toxicity criteria, statistical analysis plan, sample-size justification, multiplicity approach, missing-data methods, and secondary-outcome analysis populations are not reported in the registry record. The full later administration schedule for the complete-remission group is also not reported in the registry record because its description is incomplete.
For safety interpretation, the registry lists counts and serious event terms with percentages but does not provide the denominator definitions, exposure-adjusted rates, event timing, or treatment attribution in the information. These limitations mean the figures are descriptive and should not be read as estimates of comparative risk. The registry’s outcome list, despite covering clinical and pharmacokinetic measures, does not include numerical results for those measures in the registry record used for this analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients With AML in Complete Remission With High Risk to Relapse — NCT01690624.
- Registry record last updated 2025-01-27; status last verified 2024-12.
- Results first posted 2025-01-27.
- 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
NCT01690624 is a phase I, open-label, non-randomized, sequential dose-escalation trial of BI 836858 in patients with refractory or relapsed AML and patients with AML in complete remission with high risk to relapse. Boehringer Ingelheim is listed as sponsor. The record lists enrollment of 30 and status as completed.
The primary endpoint was determination of the MTD in milligrams, using an evaluable set defined as non-replaced patients who completed the first two treatment cycles. The registry record states that the trial was discontinued before reaching that endpoint. It lists 18 outcome measures and records 0 analyses. Safety counts and serious adverse event terms are reported by cohort, but the non-randomized design does not support like-for-like dose comparisons.