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 Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia (NCT00184054), a na phase 2 study. The primary outcome is Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00184054 |
| Phase | Phase 2 |
| Condition | Acute Myelogenous Leukemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Southern California |
| Results posted | Yes |
2. Clinical Question
Population
Adults with acute myelogenous leukemia (AML) that had not responded to previous treatment or who were unable to receive chemotherapy, as described in the registry summary. Response assessment was specified for subjects who received at least 2 treatment cycles.
Intervention
Arsenic trioxide (ATO) with ascorbic acid. The regimen describes ATO at 0.25 mg/kg/day intravenously for 25 days over a 35-day period, with ascorbic acid at 1000 mg/day intravenously every other day that ATO was given.
Comparator
There was no separate comparator arm. The registry describes a single-group study, with allocation recorded as NA and masking as none.
Primary question
Among eligible participants receiving at least 2 cycles, how many had a complete remission (CR) or complete remission with incomplete blood count recovery (CRi), assessed up to 1 year?
The study was registered as a phase II trial of the combination in adult non-APL AML. The registry summary describes its purpose as assessing whether the combination was effective and studying how the drugs affect participants. That stated purpose is not itself evidence of benefit: the registry record does not report the primary response count, an estimated response rate, or an analysis of that endpoint.
The clinical question is therefore descriptive rather than comparative. Without a control group, the registry cannot directly compare the combination with another treatment or with no study treatment. The record also does not provide a reported result that would establish how many participants met the response definition. The clinical question and the answer available from the registry are distinct: the question is specified, but its primary outcome result is not reported in the registry record.
3. Trial Design
This is a phase II, single-group study of arsenic trioxide plus ascorbic acid in adult non-APL AML. The registry lists University of Southern California as the sponsor. Allocation is recorded as NA, masking as none, and the study model as single group. There is no randomized control arm or like-for-like comparator described. The study status is terminated; the reason for termination is not reported in the registry record.
The registry records enrollment of 11 participants, a start date of 2002-04, and primary completion in 2009-06. The intervention description specifies intravenous ATO at 0.25 mg/kg/day for 25 days over a 35-day period, and intravenous ascorbic acid at 1000 mg/day every other day that ATO was given. The registry lists acute myelogenous leukemia as the condition.
The response population is described as all subjects who received at least 2 cycles of treatment. Participants who did not complete at least 2 cycles were not evaluated for response. The endpoint description also says that patients who failed to achieve CR or CRi after 2 cycles were considered treatment failures. The number of enrolled participants who completed the required treatment cycles, and the number included in the response analysis, are not reported in the registry record.
No protocol details beyond those recorded are available for interpreting the design. The registry does not report a sample-size justification, a statistical analysis plan, interim analyses, or a reason for termination. Those omissions mean that enrollment and study status can be described, but cannot be used to infer the original recruitment target, decision rules, or why the study ended.
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: The study has no pre-assignment. All subjects were given the same treatment.
Overall Study
| Stage | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|
| STARTED | 11 |
| COMPLETED | 10 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: All subjects who received at least 2 cycles of treatment as part of this study are included in the analysis of response.
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: All participants were included in the analysis.
| Characteristic | Unit | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|---|
| Participants analysed | 11 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 |
| Age, Categorical: >=65 years | Participants | 7 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 6 |
| Region of Enrollment: United States | participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With a Response (Complete Remissions (CR) and Complete Remission With Incomplete Blood Count Recovery (CRi), measured over Up to 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with a response, defined as complete remission (CR) or complete remission with incomplete blood count recovery (CRi), assessed up to 1 year. CR requires ANC of at least 1000/mcl, platelet count of at least 100,000/mcl, and bone marrow with fewer than 5% blasts. CRi uses the same criteria, but ANC may be below 1,000/mcl and/or platelet count may be below 100,000/mcl.
This endpoint groups two related response categories. CR represents remission meeting the stated blood count and marrow criteria; CRi allows incomplete blood count recovery while retaining the other stated remission criteria. Reporting the number who meet either definition gives a count-based description of response in the eligible response population. It does not, by itself, show how response compares with another treatment, because this study has a single group.
The registry specifies that patients who failed to achieve CR or CRi after 2 cycles were considered treatment failures. Participants who did not complete at least 2 cycles were not evaluated for response. The analysis population is described as subjects who received at least 2 cycles. The actual number assessed and the number meeting either response definition are not reported in the registry record. As a result, the endpoint definition is available, but its observed outcome is not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the study as a phase II investigation of ATO with ascorbic acid and records 11 participants enrolled. It also describes a primary response endpoint and the population intended for response assessment. However, it does not report the number of participants who achieved CR or CRi, a response proportion, an uncertainty interval, or a statistical test for the primary endpoint. There is therefore no registry-reported primary response estimate to interpret.
This absence matters because the study question is about response, not merely whether treatment was administered or whether events were recorded. Enrollment alone cannot establish an outcome. Nor can the response definition be treated as a result. The distinction between a prespecified measure and its observed value is essential: a clear endpoint does not tell the reader how often that endpoint occurred.
The design also limits what any response count could establish. A single-group study can describe outcomes among participants who received the combination, but it cannot isolate the treatment’s effect from other influences through a concurrent randomized comparison. In the absence of a comparator, there is no direct estimate of how outcomes would differ under another treatment. The registry explicitly indicates that the study is not a randomized comparison, so its arms should not be treated as a like-for-like control comparison.
The registry does report safety-related entries. It lists 11 participants at risk and 11 affected in each of its serious and other adverse-event groupings. Among the serious terms listed, sepsis is recorded at 36.4%; conjunctivitis infective at 18.2%; and anorexia, alanine aminotransferase increased, differentiation syndrome, and electrocardiogram QT corrected interval prolonged at 9.1% each. These entries describe the registry’s safety reporting, but do not supply the missing primary response result. Serious adverse events and the primary remission outcome address different questions.
These safety figures should also be read as descriptive registry entries, not as proof that the study treatment caused each event. The record does not supply a comparison group for attributing excess risk, and the listed terms do not provide a complete account of timing, duration, or clinical course. The secondary outcome is described as the number of participants with severe (Grades 3-5) adverse events, but its result is not reported in the registry record. Seriousness and severity are distinct classifications and should not be assumed to be interchangeable.
The study is marked terminated, but the reason is not reported in the registry record. The record also does not report why enrollment was 11, how many participants completed at least 2 cycles, or whether any planned interim or stopping rules were used. Taken together, these omissions support a limited reading: the registry documents the intervention, intended response measure, enrollment, and selected safety entries, while leaving the primary response outcome and important analysis details unavailable.
9. Statistical Methods Explained
For a binary endpoint such as whether a participant meets the CR-or-CRi response definition, the basic outcome is a count of participants with the event. A response proportion can be estimated by relating that count to the number assessed, but the registry does not report either the response count or the response-analysis denominator. No response proportion can therefore be interpreted from the registry record. The enrolled count of 11 is not necessarily the response denominator, because the stated response population requires receipt of at least 2 cycles.
A confidence interval is a statistical description of the uncertainty around an estimate. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. For a response proportion, interval width depends in part on the number of participants assessed and the observed response count. Since neither is reported for the primary endpoint, there is no registry-reported response estimate or confidence interval to discuss. Any general statement about precision should not be mistaken for an endpoint result in this study.
A hypothesis test addresses whether observed data are sufficiently incompatible with a specified null hypothesis, under the assumptions of the test. A p-value does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. Here, no primary endpoint test or p-value is reported in the registry record. In addition, with no comparator arm described, a treatment-versus-control hypothesis test is not part of the design information recorded.
The primary endpoint is a count rather than a continuous measurement or a time-to-event outcome. For a count, an analysis might describe the number of participants meeting the endpoint and the number assessed. If an analysis instead models counts across groups or time, the choice of model would depend on the data structure and assumptions. General statistical practice distinguishes an observed count from a model-based estimate; neither should be inferred when the registry does not report the relevant outcome data or analysis.
There is no reported analysis method for the primary endpoint. The registry record does not state whether estimates were adjusted, whether any covariates were considered, how missing outcomes were handled, or whether a particular confidence-interval or testing procedure was selected. It would be inappropriate to assign a method to the investigators without that information. The endpoint definition and analysis population can be described, but they do not reveal the actual statistical procedure used.
What does over-dispersion mean?
General explanation: over-dispersion occurs when observed variation in count data is greater than a chosen statistical model expects. When it is ignored, standard errors can be too small and confidence intervals or tests can appear more precise than warranted. It is relevant to some count models, but the registry does not report a count-model analysis for this endpoint, so over-dispersion cannot be assessed as a feature of this study’s primary analysis.
How should planning calculations be read?
General explanation: a sample-size calculation asks how many observations might be needed to detect a specified effect under stated assumptions. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It varies the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study had that probability of detecting an effect. They do not describe the actual single-group design, and they do not substitute for a protocol-based sample-size justification.
For binary outcomes, a planning calculation must rely on assumptions about the event rates in the groups being compared and the effect size of interest. In this case, the recorded assumption refers to the observed effect, but the primary response effect is not reported in the registry record. The resulting planning display therefore should not be treated as a registry-reported analysis result or as proof that the actual study could detect a particular treatment effect. The registry does not report the original sample-size justification or the assumptions used when the study was designed.
The response definition also creates an analysis-population issue. Participants who did not complete at least 2 cycles were not evaluated for response, while those who received at least 2 cycles are identified as the response population. This means that enrollment and response assessment are different denominators. General statistical interpretation should keep those groups separate; otherwise, a response count could be read against the wrong population. The registry does not report how many participants met the cycle requirement or how non-evaluable participants were handled in any broader analysis.
Because no primary outcome result or analysis is recorded, there is no basis to assess model fit, precision, statistical significance, or robustness for the response endpoint. Any such assessment would require the missing outcome data and the analysis details. The registry’s description is sufficient to explain what the endpoint was intended to measure, but not to reconstruct or validate an unreported analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary response outcome and a secondary outcome concerning participants with severe (Grades 3-5) adverse events. It does not report a statistical analysis plan, a hierarchy for testing outcomes, an adjustment for multiple testing, or interim analyses. Whether multiplicity was considered in the study’s planned inference is not reported in the registry record. No claim about controlling the chance of false-positive findings can be made from the available analysis information.
For context, multiplicity arises when several outcomes, comparisons, or repeated tests are examined. If each is tested without an appropriate strategy, the chance of at least one apparently unusual result can increase. General methods to address this include prespecifying a primary outcome, defining a testing sequence, or adjusting inference. These are general principles; the registry does not say which, if any, were used in this study. The mere designation of a primary endpoint does not establish how other outcomes were handled statistically.
The response population is restricted to subjects who received at least 2 cycles. Participants who did not complete at least 2 cycles were not evaluated for response, and the endpoint description treats failure to achieve CR or CRi after 2 cycles as treatment failure. The number of participants in each of these situations is not reported in the registry record. Nor are reasons for noncompletion, missing response assessments, or any imputation or sensitivity analyses reported. The outcome data should therefore not be assumed complete or missing at random.
The record identifies enrollment as 11, but the count assessed for the primary endpoint is not reported. This distinction prevents using enrollment as a substitute for the response denominator. The registry also records no analyses, so it does not provide an analysis population flow or outcome-specific denominators. These gaps constrain interpretation of both completeness and the possible impact of missing data.
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 |
|---|---|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | 11 | 11 | 100.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arsenic Trioxide (ATO) Plus Ascorbic Acid | 11 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|---|
| Sepsis | Infections and infestations | 4 of 11 |
| Conjunctivitis infective | Infections and infestations | 2 of 11 |
| Anorexia | Metabolism and nutrition disorders | 1 of 11 |
| Alanine aminotransferase increased | Investigations | 1 of 11 |
| Differentiation syndrome | General disorders | 1 of 11 |
| Electrocardiogram QT corrected interval prolonged | Investigations | 1 of 11 |
| Neuropathy sensory | Nervous system disorders | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arsenic Trioxide (ATO) Plus Ascorbic Acid |
|---|---|---|
| Headache | Nervous system disorders | 5 of 11 |
| Nausea | Gastrointestinal disorders | 5 of 11 |
| Vomiting | Gastrointestinal disorders | 5 of 11 |
| Fatigue | General disorders | 3 of 11 |
| Anorexia | Metabolism and nutrition disorders | 2 of 11 |
| Localized edema | General disorders | 2 of 11 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 2 of 11 |
| Cellulitis - hand | Infections and infestations | 1 of 11 |
| Electrocardiogram QT corrected interval prolonged | Investigations | 1 of 11 |
| Urinary Tract Infection | Infections and infestations | 1 of 11 |
Serious events with the highest arm-level rate: sepsis (36.4%), conjunctivitis infective (18.2%), anorexia (9.1%), alanine aminotransferase increased (9.1%), differentiation syndrome (9.1%).
The safety record lists 11 participants at risk and 11 affected in each of the serious and other adverse-event groupings for the ATO-plus-ascorbic-acid group. The serious terms listed include sepsis at 36.4%, conjunctivitis infective at 18.2%, and anorexia, alanine aminotransferase increased, differentiation syndrome, and electrocardiogram QT corrected interval prolonged at 9.1% each. These are the registry’s reported entries; they do not provide a full narrative of each event or its timing.
The secondary outcome is the number of participants with severe (Grades 3-5) adverse events. Its outcome result is not reported in the registry record. Seriousness and severity are related but distinct concepts: seriousness generally concerns regulatory or clinical consequences, while severity describes intensity. A serious event is not automatically a Grade 3-5 event, and a severe event is not necessarily classified as serious. The categories should not be merged without participant-level definitions and results.
The listed percentages are descriptive and do not establish that the intervention caused the events. There is no comparator arm for a direct safety comparison, and the registry does not report further context about attribution, duration, or outcomes. The number of deaths is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II single-group study of ATO with ascorbic acid enrolled 11 participants and specified a primary endpoint based on CR or CRi. It also records the regimen, response eligibility rule, study status, and selected adverse-event terms. These are useful descriptions of what the study set out to assess and what safety entries were recorded.
Those details do not establish the primary outcome. The number of participants achieving CR or CRi, the response denominator, and an estimate of response are not reported in the registry record. The study’s stated purpose should not be confused with an observed finding. Without the endpoint result, readers cannot determine from this record how often the defined response occurred or how precisely it was estimated.
The single-group design also means that outcomes cannot be compared directly with a concurrent control group. Even if a response count were available, it would describe participants in this study and would not by itself separate treatment effects from other explanations. No randomized comparison is described. The record does not support a claim about the treatment’s comparative effect.
The adverse-event entries describe events recorded in the registry, but they do not establish causation. The listed percentages are not a substitute for a comparative safety analysis, and the severe adverse-event outcome has no reported result. Similarly, the study’s terminated status does not explain why it ended; that reason is not reported in the registry record.
In short, the record supports a careful account of the trial’s design and its registered outcome definitions, but not a conclusion about response or comparative effectiveness. It also offers selected safety reporting without enough information to make a causal comparison. Missing outcome and analysis details should remain explicit rather than being filled in by inference.
13. Why This Trial Matters Statistically
This study illustrates a basic distinction in clinical-trial interpretation: an endpoint definition is not an endpoint result. The registry specifies CR and CRi criteria, a response assessment timeframe, and a population based on receiving at least 2 cycles. Yet it does not report how many participants met those criteria. A reader can understand what was intended to count as response without knowing the observed response experience.
It also highlights why denominators matter. Enrollment is recorded as 11, while the response population excludes participants who did not complete at least 2 cycles. Since the number reaching that threshold is not reported, the enrolled count cannot stand in for the analysis denominator. Keeping enrollment, treatment exposure, and outcome assessment distinct is important when reading any trial record.
The single-group design reinforces the difference between description and comparison. A study can describe the outcomes observed among participants receiving a regimen, but comparison with an alternative requires a suitable comparator and a defined analysis. The registry records no randomized comparison, so readers should not interpret the record as a direct estimate of relative treatment effect.
Finally, the study’s safety entries show why outcome labels and reporting completeness matter. Serious events, severe events, and response are different outcome concepts, and the registry has no reported result for the severe adverse-event endpoint. The available information supports a transparent account of what is and is not documented, rather than a definitive claim about efficacy or safety.
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 important limitation for interpretation is that the registry record does not report the primary response count, the response-analysis denominator, an estimate, or a statistical test. It also does not report the result for the secondary severe adverse-event outcome. As a result, the central outcome questions cannot be answered from the registry record.
The study is single group, with no randomized comparator described. This design cannot provide a direct like-for-like comparison. The registry status is terminated, but the reason for termination is not reported in the registry record. Enrollment is 11; the number who received at least 2 cycles and the number assessed for response are not stated.
Other important analysis details are also absent: the registry does not report a sample-size justification, statistical analysis plan, interim analyses, handling of missing outcomes, or a reason for termination. It does not report participant-level safety details, the context or attribution of the listed events, or the number of deaths. The safety entries therefore have limited context, and cannot establish causation or support a comparative risk estimate.
These limitations are specific to what the registry documents. They do not establish that analyses or additional information never existed; those details are simply not reported in the registry record. Interpretation should be restricted to the registered design, endpoint definitions, enrollment, and listed safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia — NCT00184054.
- Registry record last updated 2014-07-25; status last verified 2014-07.
- Results first posted 2014-07-17.
- 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
The registry describes a phase II, single-group study of arsenic trioxide with ascorbic acid in adult non-APL AML, sponsored by University of Southern California. It records enrollment of 11 participants, study status as terminated, and response assessment up to 1 year among subjects who received at least 2 cycles. The primary endpoint is the number achieving CR or CRi.
The primary response result and the severe adverse-event outcome result are not reported in the registry record. The record lists serious adverse-event terms and percentages, but provides no comparator for a direct treatment comparison. The reason for termination, sample-size justification, statistical analysis plan, and missing-data methods are also not reported in the registry record.