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 Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders (NCT02425904), a non-randomized phase 2 study. The primary outcome is Response Rate (OR) of LCH Cohort.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02425904 |
| Phase | Phase 2 |
| Condition | Langerhans Cell Histiocytosis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dana-Farber Cancer Institute |
| Results posted | Yes |
2. Clinical Question
The study asks whether clofarabine is associated with disease responses in people with recurrent or refractory Langerhans Cell Histiocytosis (LCH) and in people with LCH-related disorders who require systemic chemotherapy. Its primary response question concerns the LCH cohort, not a comparison between clofarabine and another treatment.
Population
The registry describes people with multifocal or multisystem LCH that recurred or was refractory after at least one prior systemic chemotherapy regimen. A separate cohort included participants with LCH-related disorders who required systemic chemotherapy. The registry lists an enrollment of 25 overall.
Intervention
The intervention was clofarabine. The registry describes intravenous administration on days 1–5 at 25 mg/m2/day per cycle in the LCH cohort. Further regimen details are not reported in the registry record.
Comparator
No randomized control group is described. The registry lists a non-randomized allocation and a single-group model, with clofarabine listed for both disease cohorts. The cohorts are not a like-for-like control comparison.
Primary question
For the LCH cohort, the primary endpoint is the proportion of participants achieving a response defined by protocol criteria. Disease was evaluated at baseline and at the end of cycle 2. The response result and its 95% confidence interval are not reported in the registry record.
3. Trial Design
This is a phase II study sponsored by Dana-Farber Cancer Institute. The registry lists a non-randomized allocation, no masking, and a single-group model. It lists an enrollment of 25 and an active, not recruiting status. The registry gives a start date of 2015-05 and a primary completion date of 2020-01; these dates do not establish that all outcome data are posted.
Two disease cohorts are described, and both receive clofarabine. The recurrent or refractory LCH cohort is described as participants with multifocal or multisystem disease that recurred, or was refractory, after at least one prior systemic chemotherapy regimen. The other cohort comprises participants with LCH-related disorders requiring systemic chemotherapy. The registry gives examples including Rosai Dorfman Disease (RDD) after lack of response or recurrence following corticosteroids. It also mentions Erdheim Chester Disease (ECD) and confirmed BRAF V600E, but further detail is not reported in the registry record.
The intervention description states that clofarabine is administered intravenously on days 1–5 at 25 mg/m2/day per cycle for the LCH cohort. The complete schedule is not reported in the registry record. The primary endpoint applies to the LCH cohort. Listed secondary outcomes are 1-year progression-free survival, 1-year overall survival, and the number of participants with at least one grade 3 or higher treatment-related toxicity.
Because allocation was not randomized and no control group is described, the study does not provide a randomized estimate of a treatment contrast. The separate disease cohorts should not be treated as interchangeable comparison groups: they were defined by different diagnoses and eligibility descriptions. The registry record does not report details of the statistical analysis plan, masking procedures beyond none, or a sample-size justification.
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 | Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | LCH-related Disorders + Clofarabine |
|---|---|---|
| STARTED | 20 | 5 |
| Efficacy analysis | 20 | 4 |
| COMPLETED | 17 | 2 |
| NOT COMPLETED | 3 | 3 |
Reasons for not completing this period:
| Reason | Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | LCH-related Disorders + Clofarabine |
|---|---|---|
| Lost to Follow-up | 1 | 0 |
| Withdrawal by Subject | 2 | 0 |
| Death | 0 | 3 |
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 | Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | LCH-related Disorders + Clofarabine | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 5 | 25 | |
| Age, Customized | years | 3.4 (0.6 to 10.6) | 38.6 (10.7 to 58.2) | 4.3 (0.6 to 58.2) |
| Sex: Female, Male: Female | Participants | 15 | 2 | 17 |
| Sex: Female, Male: Male | Participants | 5 | 3 | 8 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 0 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 15 | 5 | 20 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Region of Enrollment: United States | participants | 17 | 5 | 22 |
| Region of Enrollment: Canada | participants | 3 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Response Rate (OR) of LCH Cohort, measured over Disease was evaluated at baseline and the end of cycle 2. Treatment continued after cycle 2 until disease progression or unacceptable toxicity. LCH treatment duration has a median of 5.8 months with range 2.1-7 months..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | proportion of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the response rate (OR) in the LCH cohort, defined as the proportion of participants achieving a protocol-defined response on treatment. The registry describes response categories: disease resolution (NAD) or regression (AD better) as better response; stable or unchanged disease as intermediate response; and disease progression as worse response. The precise rule for which category or categories count in the primary response numerator is not reported in the registry record.
Disease was assessed at baseline and at the end of cycle 2. Treatment could continue after cycle 2 until progression or unacceptable toxicity. The registry reports an LCH treatment duration median of 5.8 months, with a range of 2.1-7 months. That duration describes treatment exposure, not the response rate or the time at which every participant’s response was assessed.
A proportion is useful for expressing how many participants in a defined group meet an outcome criterion. Its interpretation depends on a clear numerator, denominator, assessment time, and response definition. The endpoint is clinically descriptive, but the posted record does not give the number meeting the response criterion, the denominator analyzed, or an estimate with its stated 95% confidence interval. The size and precision of the response result therefore cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies response rate in the LCH cohort as the primary endpoint, but does not report a response estimate. It also does not report the number of LCH participants classified as having better, intermediate, or worse response. As a result, the direction and magnitude of the primary outcome cannot be characterized from the registry record. Although the endpoint specifies a 95% confidence interval, the interval itself is not reported in the registry record.
This absence matters for interpretation. A response proportion describes the observed frequency of a defined outcome in the analyzed participants; it is not, by itself, an estimate of what would have happened to the same participants under another treatment. With no randomized comparator described, changes cannot be separated from other possible explanations using a between-group treatment contrast. The non-randomized, single-group design is therefore suited to describing outcomes in the enrolled cohort, rather than establishing a causal comparison with a control treatment.
The endpoint is limited to the LCH cohort, while the registry also describes a separate cohort with LCH-related disorders. Outcomes in that second cohort should not be combined with the primary LCH endpoint unless the analysis plan defines such a combination; that plan is not reported in the registry record. The diagnoses and eligibility descriptions differ, so a direct comparison between the cohorts would not function as a controlled comparison.
The registry lists 1-year progression-free survival and 1-year overall survival as secondary outcomes, but does not report estimates for either outcome. It also lists the number of participants with at least one grade 3 or higher treatment-related toxicity, without reporting that outcome’s result. The posted safety information includes participant counts and serious-event terms, but those entries do not supply the missing primary response estimate.
Consequently, the registry record supports a description of the study question, design, endpoint definition, and some safety reporting. It does not support a conclusion about the observed response frequency or its precision. A missing result is not evidence of a null result, and the registry does not explain why the primary outcome result is absent.
9. Statistical Methods Explained
The registry describes a binary proportion endpoint: the proportion of LCH participants achieving a protocol-defined response. It specifies a 95% confidence interval as the measure of uncertainty, but does not report the estimate, interval limits, or analysis population. The statistical analysis plan is not reported in the registry record.
What does a response proportion describe?
In general, a proportion is the number of participants meeting a defined outcome divided by the number assessed in a defined population. The definition of success and the denominator are essential. Here, the registry gives response categories but does not fully state which categories enter the primary response numerator, and it does not report the observed numerator or denominator. The response proportion therefore cannot be reconstructed or interpreted quantitatively from the posted record.
In general, a confidence interval expresses uncertainty around an estimate under the statistical method used. It is not a guarantee that the true value lies in a particular interval, and its width depends on the information available and the method’s assumptions. The registry’s endpoint description names a 95% confidence interval, but its limits are not reported in the registry record. No precision claim about the primary endpoint can therefore be made.
Why does the assessment time matter?
The registry says disease was evaluated at baseline and at the end of cycle 2. This defines an assessment point for response, while treatment could continue after cycle 2 until disease progression or unacceptable toxicity. A response measured at a scheduled assessment is not interchangeable with a time-to-event outcome such as progression-free survival. The registry separately lists 1-year progression-free survival and overall survival as secondary outcomes, but provides no estimates or analysis details for them.
The treatment-duration summary for the LCH cohort is a median of 5.8 months, with a range of 2.1-7 months. In general, a median identifies the middle value in an ordered set, while a range gives the minimum and maximum observed values. These descriptive summaries do not indicate how many participants responded, and they do not replace an endpoint-specific analysis.
What can the design estimate?
The study is listed as non-randomized, with no masking and a single-group model. In general, a single-group study can describe outcomes among participants receiving an intervention. Without a randomized control group, it does not provide the same protection against differences in prognosis and other influences that a randomized comparison can offer. The two disease cohorts both receive clofarabine, but their different diagnoses and eligibility descriptions mean one should not be treated as the control for the other.
General statistical interpretation also depends on how participants were selected, followed, and included in each analysis. Those details, including the analysis populations and handling of missing endpoint assessments, are not reported in the registry record. The registry lists an enrollment of 25, but it does not state how many participants contributed to the primary endpoint result.
What do planning calculations mean?
In general, sample-size calculations describe what study size may be needed under specified assumptions; they are not observed treatment effects or evidence that a study had a particular probability of detecting an effect. The listed planning approach is an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the planning quantity is total events, while other planning quantities are participants per arm. These calculations are planning illustrations, not the trial’s original design justification or observed power. The design assumptions for the trial itself are not reported in the registry record.
For binary outcomes, general methods may differ in their treatment of small samples and uncertainty. The method used for the primary confidence interval is not reported in the registry record. No unadjusted recalculation or sponsor analysis result is available in the posted information to discuss. Without the observed response data and analysis details, a method-specific appraisal of the primary estimate is not possible.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: the primary response rate in the LCH cohort, 1-year progression-free survival, 1-year overall survival, and participants with at least one grade 3 or higher treatment-related toxicity. When a study evaluates multiple outcomes, general statistical practice considers whether interpretation should account for the number of hypotheses or analyses. The multiplicity strategy for this study is not reported in the registry record, so it is not possible to determine whether or how the listed outcomes were handled as a family.
The record lists zero analyses. It does not report estimates for the primary or secondary efficacy outcomes, or the result for the specified grade 3 or higher treatment-related toxicity outcome. This does not establish that analyses were not performed; it means analyses are not reported in the registry record.
The analysis populations are not reported in the registry record. In particular, the record does not state how many participants were included in the primary response analysis, whether all enrolled participants were analyzed, or how participants without an end-of-cycle-2 assessment were treated. Missing-data methods and reasons for missing assessments are not reported in the registry record. In general, these details matter because the denominator and assumptions about missing outcomes can affect an estimated proportion.
Interim analyses, stopping rules, and a detailed statistical analysis plan are also not reported in the registry record. The record gives an enrollment of 25, but does not provide a sample-size justification for the trial. These gaps limit assessment of prespecification, selective outcome reporting, and the precision intended by the original design.
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 |
|---|---|---|---|
| Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | 15 | 20 | 75.0% |
| LCH-related Disorders + Clofarabine | 4 | 4 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | 0 of 20 |
| LCH-related Disorders + Clofarabine | 3 of 4 |
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 |
|---|---|
| Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | 20 of 20 |
| LCH-related Disorders + Clofarabine | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | LCH-related Disorders + Clofarabine |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 8 of 20 | 4 of 4 |
| Neutrophil count decreased | Investigations | 8 of 20 | 2 of 4 |
| Febrile neutropenia | Blood and lymphatic system disorders | 6 of 20 | 2 of 4 |
| Platelet count decreased | Investigations | 3 of 20 | 4 of 4 |
| White blood cell decreased | Investigations | 4 of 20 | 2 of 4 |
| Lymphocyte count decreased | Investigations | 3 of 20 | 1 of 4 |
| Alanine aminotransferase increased | Investigations | 1 of 20 | 1 of 4 |
| Aspartate aminotransferase increased | Investigations | 1 of 20 | 1 of 4 |
| Device related infection | Infections and infestations | 1 of 20 | 0 of 0 |
| Hyperkalemia | Metabolism and nutrition disorders | 1 of 20 | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Recurrent or Refractory Langerhans Cell Histiocytosis (LCH) + Clofarabine | LCH-related Disorders + Clofarabine |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 11 of 20 | 3 of 4 |
| Vomiting | Gastrointestinal disorders | 12 of 20 | 2 of 4 |
| Constipation | Gastrointestinal disorders | 11 of 20 | 1 of 4 |
| Fatigue | General disorders and administration site conditions | 9 of 20 | 3 of 4 |
| Fever | General disorders and administration site conditions | 10 of 20 | 2 of 4 |
| Cough | Respiratory, thoracic and mediastinal disorders | 8 of 20 | 0 of 0 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 7 of 20 | 1 of 4 |
| Anemia | Blood and lymphatic system disorders | 5 of 20 | 2 of 4 |
| Diarrhea | Gastrointestinal disorders | 7 of 20 | 0 of 0 |
| Sinus tachycardia | Cardiac disorders | 7 of 20 | 0 of 0 |
Serious events with the highest arm-level rate: anemia (100.0%), platelet count decreased (100.0%), febrile neutropenia (50.0%), neutrophil count decreased (50.0%), white blood cell decreased (50.0%).
The registry separates safety information for the recurrent or refractory LCH cohort and the LCH-related disorders cohort. For the LCH cohort, it lists 20 participants at risk and 15 affected for serious adverse events; it lists 20 at risk and 20 affected for other adverse events. For the LCH-related disorders cohort, the corresponding counts are 4 at risk and 4 affected for serious events, and 4 at risk and 4 affected for other events. These counts describe the registry entries; they do not establish that every event was caused by clofarabine.
The listed top serious-event terms include anemia at 100.0%, platelet count decreased at 100.0%, febrile neutropenia at 50.0%, neutrophil count decreased at 50.0%, white blood cell decreased at 50.0%, and alanine aminotransferase increased at 25.0%. The denominator and details behind these term percentages are not reported in the registry record, so they should not be converted into participant counts or compared across cohorts.
The registry lists 0 deaths in the LCH cohort and 3 in the LCH-related disorders cohort. It does not report the circumstances or attribution for these deaths in the information. The listed secondary toxicity outcome is participants with at least one grade 3 or higher treatment-related toxicity, but that result is not reported in the registry record. Serious events, other events, and treatment-related toxicities are distinct reporting concepts and should not be treated as interchangeable.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a phase II evaluation of clofarabine in recurrent or refractory LCH and LCH-related disorders, with a primary response endpoint for the LCH cohort. It gives the response categories and timing of disease evaluation, along with some safety counts and serious-event terms. It does not report the observed primary response rate or its 95% confidence interval.
Accordingly, the posted information does not establish how frequently participants met the primary response definition, how precise that estimate was, or whether response differed between any groups. No randomized comparison is described, and the disease cohorts are not a like-for-like control comparison. The registry record also does not provide reported results for the listed 1-year progression-free survival, 1-year overall survival, or grade 3 or higher treatment-related toxicity outcomes.
In general, an observed response in a single-group study is a description of outcomes in that cohort. It cannot alone identify what would have occurred under a different treatment or without the intervention. The limitations are especially important when interpreting outcomes in distinct disease groups, because cohort differences can influence observed outcomes independently of treatment.
The available adverse-event entries are relevant descriptive information, but they do not replace the missing efficacy outcome or the listed toxicity endpoint result. The death counts are reported by cohort, but the record does not provide attribution details. Neither the event-term percentages nor cohort counts should be interpreted as a comparative treatment effect.
The appropriate conclusion is therefore bounded: the registry describes the study design, question, endpoint definition, and selected safety data, while leaving the primary response result and several analysis details unreported. An unreported result should not be read as evidence that the outcome was absent, favorable, or unfavorable.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction between defining an endpoint and reporting its result. The registry specifies a response-rate question for the LCH cohort, describes response categories, names a 95% confidence interval, and gives an assessment time. Yet the response estimate, interval, and analysis denominator are not reported in the registry record. A clearly described endpoint is necessary for interpretation, but it cannot substitute for the numerical result.
The design also illustrates the limits of a non-randomized, single-group study. Such a design can document outcomes among participants receiving clofarabine, but it does not create a randomized treatment contrast. The presence of two cohorts does not supply a control comparison when those cohorts differ by disease description and both receive the intervention.
Another statistical issue is the separation of efficacy, time-to-event, and safety outcomes. Response rate, 1-year progression-free survival, 1-year overall survival, and treatment-related toxicity answer different questions and require their own definitions and analysis details. The registry lists these outcomes but does not report their analyses or results. Safety counts and serious-event terms provide a separate descriptive view, not a substitute for the absent primary endpoint estimate.
Finally, planning illustrations must be distinguished from the trial’s original design and from evidence of observed power. The listed approach describes assumptions for illustrative calculations, while the trial’s own sample-size justification is not reported in the registry record. Together, these features show why readers need endpoint results, analysis populations, uncertainty estimates, and design details to assess what a clinical study can support.
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 for interpreting this trial from the registry record is that the primary response result is not reported. The response count, denominator, proportion, and 95% confidence interval are absent. Although the response categories are described, the exact rule for which category or categories count toward the primary response numerator is not reported in the registry record.
The study is non-randomized, has no masking, and is listed as a single-group model. No randomized control group is described. This prevents a randomized estimate of the difference between clofarabine and another treatment. The two cohorts are defined by different disease descriptions and should not be treated as a substitute for control and intervention groups.
The registry lists enrollment of 25, but does not report the number analyzed for the primary endpoint, the analysis population, losses to follow-up, or missing-data handling. It also does not report the detailed statistical analysis plan, multiplicity approach, interim analyses, or trial sample-size justification. These omissions limit assessment of precision and of how the analysis was conducted.
Secondary outcomes are listed without their results. Safety entries include cohort counts and serious-event terms, but the denominator for term percentages and details of event attribution are not reported in the registry record. The record also does not explain the three deaths listed in the LCH-related disorders cohort. These reporting limitations do not establish that outcomes were not measured; they restrict what can be concluded from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders — NCT02425904.
- Registry record last updated 2026-06-23; status last verified 2026-06.
- Results first posted 2022-02-16.
- 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 NCT02425904, a phase II, non-randomized study of clofarabine in recurrent or refractory LCH and LCH-related disorders. It lists Dana-Farber Cancer Institute as sponsor, an enrollment of 25, no masking, a single-group model, and an active, not recruiting status.
The primary endpoint is response rate in the LCH cohort, with disease assessment at baseline and the end of cycle 2. Response categories are described, but the result and its 95% confidence interval are not reported in the registry record. Listed secondary outcomes include 1-year progression-free survival, 1-year overall survival, and participants with at least one grade 3 or higher treatment-related toxicity; their results are not reported.
The record includes cohort-level safety counts, serious-event terms, and deaths. It does not report a randomized comparator, detailed analysis populations, missing-data methods, multiplicity procedures, or the trial’s sample-size justification.