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 Study of Sequential Administration of Oral 6-Thioguanine After Methotrexate in Patients With LCH (NCT00588536), a na phase 2 study. The primary outcome is Determine the Incidence of Complete and Partial Response and the Duration of Response in Patients With Langerhans Cell Histiocytosis (LCH) Treated With Sequential Administration of Oral 6-TG After MTX..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00588536 |
| Phase | Phase 2 |
| Condition | Langerhans Cell Histiocytosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Langerhans Cell Histiocytosis (LCH). The registry record does not report further eligibility details, such as disease extent, prior treatment, age, or other clinical characteristics.
Intervention
The study objective describes sequential administration of oral 6-thioguanine (6-TG) after methotrexate (MTX). The listed treatment group is MTX, 6-TG, and leucovorin. The registry record does not report doses, treatment intervals, duration, or additional details of the sequence.
Comparator
No separate comparator group is described. The record identifies a single-group study, with allocation listed as not applicable. It therefore does not describe a randomized comparison or a like-for-like control group.
Primary question
The primary question is the incidence of complete and partial response, and the duration of response, among patients treated with sequential oral 6-TG after MTX. The outcome is expressed as a number of participants and has a timeframe of the conclusion of the study. The registry record does not report a response count or response-duration result.
This question concerns whether responses were observed in the treated group and how long responses lasted, as described by the study objective. Those are distinct aspects of outcome: an incidence describes response occurrence, while duration concerns persistence over time. The registry record does not specify how complete or partial response was defined, how duration was measured, or which participants were included in each assessment. Without those details and the outcome results, the record does not support a quantitative estimate of response frequency or duration. The study is identified as Phase 2 and is reported as completed; that status does not itself supply an outcome finding.
3. Trial Design
The registry record describes a Phase 2, single-group study with no masking. Allocation is listed as not applicable, and the record does not identify a separate control arm. The listed group received MTX, 6-TG, and leucovorin. The study objective describes oral 6-TG administered sequentially after MTX, but detailed treatment procedures are not reported in the registry record.
Enrollment is listed as 5. This is the registry’s enrollment figure; it should not automatically be treated as the number included in every outcome analysis, because analysis-population details are not reported in the registry record. The study is marked completed. Its recorded start is 1995-01, and its primary completion is 2008-07. Memorial Sloan Kettering Cancer Center is listed as the sponsor.
A single-group design can describe outcomes among people receiving the study regimen. Without a concurrent comparison group, however, it does not provide a direct randomized estimate of how those outcomes differ from outcomes under another treatment or usual care. The absence of masking is also part of the recorded design. The registry record does not explain why these design choices were made or provide further information about implementation.
The record gives no sample-size justification, recruitment details, eligibility criteria, treatment adherence information, or protocol-level explanation of the study design. The sample-size calculations accompanying the posted material are described as planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are not the trial’s own design rationale or observed power. Because this was a single-group study, those two-arm planning assumptions should not be read as a description of the trial’s actual allocation.
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
| Stage | MTX, 6-TG and Leucovorin |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | MTX, 6-TG and Leucovorin |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 4 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
| Region of Enrollment: United States | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Determine the Incidence of Complete and Partial Response and the Duration of Response in Patients With Langerhans Cell Histiocytosis (LCH) Treated With Sequential Administration of Oral 6-TG After MTX., measured over Conclusion of the study.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is described as determining the incidence of complete and partial response and the duration of response in patients with LCH treated with sequential oral 6-TG after MTX. The registry lists the outcome unit as participants, the parameter as a number, and the timeframe as the conclusion of the study. In this context, incidence concerns how many participants had a response, while duration concerns how long a response persisted.
These measures address different features of clinical outcome. A response count can describe whether complete or partial responses were recorded in the treated group. Duration can add information about persistence, rather than treating a response at one assessment as the whole outcome. These are general statistical distinctions; the registry record does not describe the assessment schedule or the exact method used to determine response duration.
The registry record does not report the observed number of complete or partial responses, nor does it report a duration estimate. It also does not state response criteria, whether complete and partial responses were counted separately, or how participants without a documented response were handled in duration summaries. Consequently, the endpoint description identifies what the study intended to assess, but does not provide enough posted outcome information to quantify the results or their precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a treatment sequence and a primary response objective, but it does not report the primary response findings. In particular, no observed count of complete or partial responses and no response-duration result are listed. The study’s completed status should not be mistaken for evidence that a particular response occurred: completion describes the study’s status, not the direction or size of its results.
Enrollment is listed as 5. That figure indicates the recorded enrollment, not necessarily the analysis population for every outcome. The record does not state how many participants contributed to the primary endpoint, whether every participant completed follow-up, or how response evaluability was determined. As a result, the registry record does not support calculation or interpretation of a response proportion, response duration, confidence interval, or treatment-effect estimate.
Even if a response count were available, a single-group study would describe the outcomes observed in that group rather than establish a comparative effect against another treatment. There is no separate comparator group in the record, and allocation is listed as not applicable. Differences between treated and untreated or differently treated patients cannot be estimated directly from this design. Clinical outcomes can also be influenced by patient characteristics, disease course, and other care; the registry record does not report information that would allow those factors to be assessed.
The study is labeled Phase 2, but that label does not replace the missing outcome data or establish a conclusion about efficacy. Interpretation of response would depend on the response definitions, assessment timing, follow-up completeness, and analysis population. Those details are not reported in the registry record. The listed timeframe, the conclusion of the study, does not specify how long individual participants were followed or how response duration was summarized.
The adverse-event record contains separate serious and other adverse-event counts for the treatment group. Those figures describe reported safety events, not the primary response endpoint. The registry lists 2 participants at risk and affected for serious adverse events, and 5 at risk and affected for other adverse events. Three serious-event terms are listed with percentages. These entries should be read as recorded safety reporting, not as a substitute for a full account of all clinical outcomes or a comparison of risk across treatments. The record does not report deaths.
Any sample-size figures calculated from the observed effect are planning illustrations, not observed power and not evidence that the study was adequately powered. No response effect is reported in the registry record, so the primary endpoint’s statistical precision cannot be assessed from the posted results. Overall, the registry documents the study question, design, enrollment, and selected safety information, but leaves the main outcome result unavailable.
9. Statistical Methods Explained
The registry identifies the primary outcome as a number of participants and classifies it as binary. In general, a binary outcome records whether an event or condition is present or absent for each participant. For this study, the described event of interest is complete or partial response. A count is a direct way to report how many participants experienced an event, but interpreting that count usually also requires knowing the relevant analysis population and the rules used to classify outcomes. Those details are not reported in the registry record.
What does a response count tell us?
A count alone describes the number of recorded events. A proportion would relate that count to an appropriate denominator, such as the number of participants assessed under a stated analysis rule. The registry record lists enrollment as 5, but does not say whether that figure is the denominator used for the primary outcome. It also does not report an observed response count. Therefore, no response proportion can be read from the registry record, and it would be inappropriate to infer one from the enrollment information.
Complete response and partial response are named in the outcome description, but their definitions are not reported in the registry record. In general, explicit criteria matter because they determine how observations are classified and whether results can be compared across studies. Assessment timing also matters: an outcome measured at a particular visit may not have the same meaning as one assessed over a defined follow-up period. The registry gives the timeframe as the conclusion of the study, but does not describe the assessment schedule or the criteria applied at that time.
How should duration be understood?
Duration of response is a time-to-event concept in general: it concerns the interval over which a response continues, with a defined event marking its end. Its interpretation depends on how the start and end of that interval are specified, how often participants are assessed, and how incomplete follow-up is handled. The registry record names duration of response as part of the primary objective but does not report an estimate, operational definition, or analysis method. It is therefore not possible to tell from the record how long responses lasted or how uncertainty around duration was assessed.
For time-to-event outcomes, some participants may not have an observed event by the end of follow-up. General methods can account for such incomplete observation, but the choice of method and the handling of follow-up are study-specific. No such analysis details are reported in the registry record. The outcome’s timeframe, stated as the conclusion of the study, does not itself identify the follow-up endpoint for each participant.
What does a single-group design imply?
In a single-group study, outcomes can be described for participants receiving the regimen, but there is no randomized group in the record against which to estimate a treatment contrast. Randomization is a general method for balancing known and unknown participant characteristics across groups, on average. Since this record describes one group and allocation as not applicable, it does not support a randomized comparison. Observed outcomes, if reported, would need to be interpreted as outcomes in this study group, not as proof that the regimen caused them.
Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessment or reporting. Its relevance depends on the outcome and study procedures. The registry does not describe further methods for reducing assessment or reporting bias, so no additional safeguards should be assumed.
What can be inferred about statistical testing?
The registry record lists no analysis records. It does not report a hypothesis test, confidence interval, adjustment method, or statistical plan for the primary outcome. A confidence interval is a general way to express uncertainty around an estimate: it indicates a range of values compatible with the data under the method’s assumptions. It does not guarantee that the true value lies in that range, and its width depends partly on the amount and variability of information available. Because the record does not report the primary estimate or its uncertainty, the precision of the response result cannot be evaluated.
For a binary outcome, methods for estimating uncertainty generally depend on the event count, the denominator, and the chosen statistical approach. When data are sparse, standard approximations may perform poorly; exact or other small-sample methods may be considered in general, depending on the analysis question. The registry record does not state which method was planned or used. No particular method should be attributed to the investigators based on the posted record.
Planning calculations described with the posted material use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are explicitly planning illustrations derived from the observed effect, rather than the trial’s own design calculations. For most outcomes, such illustrations are expressed as participants per arm; time-to-event illustrations are expressed as a total number of events. These general planning conventions do not establish the power of this completed single-group study. Sample-size illustrations are not observed power, and they cannot fill the gap left by the unreported primary result.
In general, over-dispersion matters when observed variability is greater than a model assumes; a model that ignores it can understate uncertainty. That concept is not a reported feature of this binary primary outcome, and the registry record does not identify an over-dispersion analysis. Similarly, no adjusted analysis or covariate model is reported. The statistically appropriate conclusion is therefore limited: the record describes a binary response objective and a duration objective, but does not provide the estimates or methods needed to judge their magnitude or precision.
10. Multiplicity, Missing Data and Analysis Populations
The primary objective includes complete response, partial response, and duration of response. These are related but not identical outcome components. The registry record does not explain whether they were treated as separate analyses, combined into one response measure, or ordered in a prespecified hierarchy. It also does not report a plan for handling the possibility of multiple statistical tests. In general, testing several outcomes can increase the chance of finding an apparently notable result by chance; adjustment or a prespecified testing strategy may address that issue. No such strategy is reported, so it should not be assumed that multiplicity was controlled or ignored.
No analysis records are listed in the registry. The record does not report which participants were included in the primary analysis, whether the analysis followed an intention-to-treat principle, or whether participants were excluded for missing or unevaluable outcomes. Enrollment is listed as 5, but the primary endpoint’s analysis population and denominator are not reported in the registry record.
Missing-data methods are also not described. In general, missing outcomes can affect an estimate if the participants without recorded outcomes differ from those with observed outcomes. Approaches may include explicit assumptions, sensitivity analyses, or other prespecified methods; the appropriate choice depends on the reason for missingness and the analysis objective. None of these methods is reported in the registry record. The posted outcome description therefore does not establish whether there were missing assessments, how they were handled, or whether follow-up was complete.
Response-duration analyses can also depend on incomplete follow-up and the definition of an event. The record does not report how participants without a documented end of response were handled. These omissions limit the ability to assess selection, missing-data, and multiplicity concerns, but they do not establish that a particular problem occurred. They identify information that is 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 |
|---|---|---|---|
| MTX, 6-TG and Leucovorin | 2 | 5 | 40.0% |
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 |
|---|---|
| MTX, 6-TG and Leucovorin | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | MTX, 6-TG and Leucovorin |
|---|---|---|
| Fever | General disorders | 1 of 5 |
| Neutrophil count decreased | Investigations | 1 of 5 |
| Platelet count decreased | Investigations | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MTX, 6-TG and Leucovorin |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 4 of 5 |
| White blood cell decreased | Investigations | 2 of 5 |
| Platelet count decreased | Investigations | 2 of 5 |
| Abdominal pain/cramping | Gastrointestinal disorders | 1 of 5 |
| Anorexia | Metabolism and nutrition disorders | 1 of 5 |
| Blood bilirubin increased | Investigations | 1 of 5 |
| Bone pain | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Sore throat | Respiratory, thoracic and mediastinal disorders | 1 of 5 |
| Creatinine increased | Investigations | 1 of 5 |
| Diarrhea | Gastrointestinal disorders | 1 of 5 |
Serious events with the highest arm-level rate: fever (20.0%), neutrophil count decreased (20.0%), platelet count decreased (20.0%).
The registry lists safety figures for the group described as MTX, 6-TG and leucovorin. For serious adverse events, 5 participants are listed as at risk and 2 as affected. For other adverse events, 5 are listed as at risk and 5 as affected. These are separate registry categories; the record does not explain the category definitions or whether the same participant could appear in both.
The most frequent serious-event terms listed are Fever, Neutrophil count decreased, and Platelet count decreased, each reported as 20.0%. These percentages should be read as the registry’s reported values, without inferring additional event counts or totals. The record does not state the duration of safety observation, the severity grading system, or whether the terms refer to participants or event episodes.
The safety entries do not establish comparative risk because the study has no separate comparator group. Deaths are not reported in the registry record. These safety figures are limited to the entries described and should not be interpreted as a complete account of all possible harms or as a measure of treatment effect.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2, single-group study was conducted to assess complete and partial response and response duration among patients with LCH treated with sequential oral 6-TG after MTX. It also records MTX, 6-TG, and leucovorin as the treatment group, enrollment of 5, and completed status. These registry entries describe the study question and its recorded design; they do not state what the primary outcome showed.
The registry record does not report the number of participants who had a complete response or partial response, or how long responses lasted. It therefore does not support a numerical claim about response frequency, duration, or precision. The absence of a posted result should not be interpreted as no responses, just as study completion should not be interpreted as evidence of benefit.
Even with a reported response count, a single-group result would not by itself show what would have happened to comparable patients under another treatment. There is no separate comparator group and no randomized treatment contrast in the registry record. A descriptive outcome in the treated group and a causal comparison between treatments are different statistical questions.
The safety entries show that serious and other adverse events were recorded, including the three serious-event terms each listed at 20.0%. The record also lists 2 participants affected for serious events and 5 affected for other events. These figures describe the registry’s safety entries; they do not provide a controlled comparison, explain event timing, or establish the overall balance of benefits and harms.
Accordingly, the most defensible reading is narrow: the registry documents the intended response objectives, a small recorded enrollment, a single-group design, and selected safety counts, while leaving the main response results and analysis details unreported. The record cannot establish whether the regimen produced responses, how durable any responses were, or how outcomes compare with another approach.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a research question and a reported result. The registry states a clear broad objective—response incidence and duration—but does not report the outcome values needed to answer it. A well-described endpoint is not a substitute for a numerical estimate, and a completed study status does not supply one.
The single-group design also clarifies the difference between describing outcomes and estimating a comparative treatment effect. A count within a treated group can summarize what was observed, but a comparison needs an appropriate reference group and a defined contrast. The record does not describe a comparator. That distinction remains important even when an endpoint is clinically meaningful and the treatment sequence is clearly stated.
Enrollment is listed as 5, making the importance of precise denominators and transparent uncertainty especially clear. In general, a small amount of information can yield imprecise estimates, and each outcome requires an explicit analysis population. The record does not report the primary outcome count, denominator, confidence interval, or analysis method, so statistical precision cannot be judged.
The record also illustrates why safety reporting needs careful interpretation. Serious and other adverse-event categories are reported separately, while the study has no comparison group and no detailed safety follow-up description in the registry record. Counts and event terms can describe what was recorded, but they do not by themselves provide a comparative assessment.
Finally, the planning illustrations described with the posted material should remain distinct from the trial’s actual results and design rationale. They are not observed power and do not repair missing endpoint reporting. Taken together, these features make the record useful for understanding the limits of inference from registry information: design, endpoint, analysis population, and results all matter, and they answer different questions.
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.
Several trial-specific details needed to interpret the primary outcome are not reported in the registry record. Response definitions are absent, as are the assessment schedule, the method for determining response duration, and the analysis population. The primary outcome is framed as a number of participants, but no complete-response count, partial-response count, or duration estimate is posted. The record therefore does not permit an assessment of outcome magnitude or precision.
The single-group design has no separate comparator, and allocation is listed as not applicable. This prevents a direct randomized comparison within the reported study. The record also lists no masking. It does not provide further detail about response assessment procedures or other measures that might limit assessment bias.
Enrollment is listed as 5, but the registry does not report participant characteristics, eligibility criteria, treatment adherence, follow-up completeness, or the number contributing to each outcome. The treatment objective specifies a sequence of oral 6-TG after MTX, and the group lists leucovorin, but doses, timing, and other treatment details are not reported in the registry record.
Analysis methods are not described, and no analysis records are listed. The record does not state how missing outcomes, multiplicity across response components, or incomplete response-duration follow-up were handled. Safety information is also limited: the record does not explain event definitions, observation time, severity grading, or the reporting basis for terms and percentages. These are limits of the registry record; they do not establish that a particular design or reporting problem occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Sequential Administration of Oral 6-Thioguanine After Methotrexate in Patients With LCH — NCT00588536.
- Registry record last updated 2015-05-04; status last verified 2015-04.
- Results first posted 2015-05-04.
- 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 record describes a completed Phase 2, single-group study of sequential oral 6-TG after MTX for LCH, with MTX, 6-TG, and leucovorin listed for the treatment group. Enrollment is listed as 5; masking is listed as none, and allocation as not applicable. The recorded study start is 1995-01, primary completion is 2008-07, and Memorial Sloan Kettering Cancer Center is the sponsor.
The primary objective concerns the incidence of complete and partial response and duration of response, with the timeframe stated as the conclusion of the study. The registry record does not report the response results or duration estimate, and no analysis records are listed. Safety entries report serious adverse events in 2 of 5 at risk and other adverse events in 5 of 5 at risk; Fever, Neutrophil count decreased, and Platelet count decreased are each listed at 20.0%. Deaths are not reported in the registry record.