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 A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia (NCT01187017), a na phase 1, phase 2 study. The primary outcome is Response Rate at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01187017 |
| Phase | Phase 1, Phase 2 |
| Condition | Aplastic Anemia, Neutropenia, Pancytopenia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Heart, Lung, and Blood Institute (NHLBI) |
| Results posted | Yes |
2. Clinical Question
Population
Participants with refractory severe aplastic anemia (SAA). The registry record says 1 participant was enrolled. Its background describes refractory SAA as disease that has not responded to initial treatment with antithymocyte globulin (ATG) and cyclosporine (CsA); the record does not provide additional eligibility details for the enrolled participant.
Intervention
Fludarabine plus cyclophosphamide (Flu/Cy). The arm description specifies fludarabine at 125 mg/m squared plus cyclophosphamide at 60 mg/kg.
Comparator
There was no separate comparator group. The trial is recorded as single-group, with allocation listed as NA and masking as none. It therefore does not provide a concurrent control comparison.
Primary question
Whether participants with refractory SAA had a hematologic response at 6 months after receiving fludarabine and cyclophosphamide. Response was to be classified as complete, partial, or no response. The registry record does not report the observed response category or response count.
The clinical context described in the record is the need for additional treatment after failure to respond to initial ATG plus CsA. It states that, for patients without a matched bone marrow transplant donor, there is no well-defined standard therapy. The background also discusses prior experience with other treatment approaches and infection risk, but those descriptions are rationale, not results from this pilot study.
The central question is consequently descriptive: what hematologic response category was observed at the specified assessment after this regimen? With no control group, the study cannot estimate a comparative treatment effect against another regimen or against no treatment. Because the registry does not report the primary outcome result, the response question cannot be answered from the posted results.
3. Trial Design
The registry describes a completed phase 1/2 pilot study of fludarabine plus cyclophosphamide in severe aplastic anemia. The title and background focus on refractory severe aplastic anemia. The record lists the study as single-group, with allocation recorded as NA and masking as none. There is no randomized allocation or masked comparison described.
The intervention arm is named Fludarabine/Cyclophosphamide in Participants with Severe Aplastic Anemia. Its description specifies fludarabine at 125 mg/m squared plus cyclophosphamide at 60 mg/kg. The registry lists both drugs as interventions. The enrollment entry is 1, and the primary outcome population description likewise says 1 participant was enrolled.
The primary completion date is 2012-07, the study start is 2010-08, and the status is completed. The primary outcome is response rate at 6 months, defined in the record as a hematologic response classified as complete, partial, or no response. Secondary outcomes include hematologic response, disease relapse, clonal evolution, and survival following Flu/Cy. Although the record lists these outcomes, it does not report their numerical results in the registry record for this analysis.
A single-group design can describe what occurred among participants receiving the regimen, but it does not by itself distinguish treatment effects from the natural course of disease, other care, or chance variation. The registry does not report a comparison arm, a masking procedure, or allocation method beyond the entries noted above. It also does not report detailed procedures for treatment delivery, follow-up, or outcome adjudication.
The pilot designation and phase 1/2 classification are part of the registry description. A sample-size justification, a protocol-based statistical analysis plan, and any interim-analysis plan are not reported in the registry record. Those omissions limit what can be said about the planned precision and inferential framework; they should not be filled in by assuming conventions used in other trials.
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 | Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: There was 1 participant enrolled in this study.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Response Rate at 6 Months, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is response rate at 6 months. The registry describes assessing blood counts at that time to evaluate hematologic response in participants with refractory severe aplastic anemia who received fludarabine and cyclophosphamide. The response classification is complete response, partial response, or no response. The record does not provide definitions or thresholds for those categories, so the specific criteria used to assign a response cannot be described from the registry entry.
This endpoint is used to represent a clinical and hematologic outcome rather than simply whether the regimen was administered. In general, a categorical response endpoint can make an outcome easier to describe consistently by assigning participants to prespecified response categories. A fixed assessment time also defines when the outcome is evaluated; it does not, by itself, establish what happens before or after that assessment.
The registry does not report the primary endpoint result: it gives no count or category for response at 6 months. Therefore, the posted record supports describing the endpoint and its intended assessment, but not stating whether the enrolled participant had a complete response, a partial response, or no response. It also does not report the detailed blood-count criteria, the handling of an assessment that could not be completed, or whether any independent review was used.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a study question and intervention but does not report the primary hematologic response result. It states that 1 participant was enrolled and that blood counts were to be evaluated at 6 months. It does not give the observed response category or count. As a result, there is no posted primary estimate from which to describe the response rate or its precision.
The design is single-group, with no separate comparator. This matters because an outcome observed after treatment is not, on its own, an estimate of how outcomes would have differed under another treatment or no treatment. In general, a concurrent comparison group helps account for background changes and supports a treatment contrast. Without one, any description is limited to the enrolled participant's observed course, and even that course is not reported for the primary endpoint in this registry entry.
The trial is listed as phase 1/2 and pilot. Those design labels do not substitute for outcome estimates. Nor do they supply missing details about the statistical plan, response criteria, or intended level of precision. The registry record does not report a sample-size justification, interim analyses, or a statistical analysis plan. It also does not report analyses for the primary or secondary outcomes.
In general, an estimate from a very small study is highly sensitive to the outcome of each participant, and a confidence interval would ordinarily communicate uncertainty around an estimate. Here, the primary result and corresponding uncertainty are not reported, so neither a numerical response estimate nor a confidence interval can be interpreted. Any sample-size figures elsewhere in the statistical materials are planning illustrations, not observed power and not additional trial outcomes. The planning assumptions described for those illustrations are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the record does not describe these as the trial's own design assumptions.
The safety entries are also limited. The registry lists serious adverse event fields, other adverse event fields, and deaths, but the event-term percentages do not provide a full account of event timing, duration, severity grades, or attribution. The entries should be read as registry counts and labels, not as a complete safety profile. With the primary response result missing and a single-group design, the record does not support a comparative benefit-harm conclusion.
The background section gives reasons for studying a lower-dose cyclophosphamide approach with fludarabine and discusses infection concerns and supportive antibiotics. These statements explain the rationale recorded by the investigators. They should not be treated as findings from this study. The registry record does not report results that would establish whether the rationale was borne out in the enrolled participant.
9. Statistical Methods Explained
Statistical methods need to be interpreted in light of the study design and the outcomes actually reported. The registry identifies this as a single-group study, not a randomized comparison. Allocation is listed as NA and masking as none. Those fields describe the absence of a randomized, masked comparison in the record; they do not establish how every assessment was conducted.
What does a single-group design estimate?
In general, a single-group study can describe observed outcomes among the participants who received the intervention. A comparative effect requires a contrast between outcomes under different treatment conditions. When there is no concurrent comparator, the observed course cannot separate an intervention's effect from other influences such as the disease course, supportive care, or chance. This is why the trial design limits causal interpretation even if an outcome were reported.
For this study, the primary outcome is a categorical hematologic response at 6 months: complete, partial, or no response. A response rate would ordinarily be based on the number of participants meeting a response definition relative to the outcome population. The registry identifies the outcome population as 1 participant enrolled but does not report the response count or the category observed. No rate can therefore be stated from this record. The complete and partial response criteria are also not reported, making it impossible to assess the operational definition beyond the broad categories named.
How should precision be understood?
In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the observed data under a specified statistical method; it does not guarantee that the true value lies in that range. With sparse information, estimates can be imprecise, and the outcome of each participant can have substantial influence. In this registry record, no primary response estimate or interval is reported, so the uncertainty cannot be quantified.
The record lists zero analysis records. It does not report the statistical method used for the primary endpoint, any adjustment, or a formal hypothesis test. No p-value, confidence interval, or model-based estimate is reported. These absences do not mean that a particular analysis was or was not conducted outside the registry; they mean that the registry record does not supply an analysis to interpret.
What do planning illustrations mean?
Sample-size illustrations are prospective planning exercises, not descriptions of what the trial observed. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events; other illustrations are expressed as participants per arm. Those assumptions do not change this trial's recorded single-group design and should not be read as a protocol-based sample-size calculation.
In general, a planning calculation asks how much information a hypothetical study might need to detect a chosen effect under specified assumptions. It does not establish the probability that the completed study detected an effect, and it is not observed power. The record does not report the trial's own sample-size justification or a target enrollment rationale. Therefore, planning outputs should be interpreted as conditional illustrations, rather than as evidence that this pilot was designed or powered for a particular comparison.
Why do outcome definitions and timing matter?
In general, a prespecified endpoint definition helps determine which observations count as events or responses, while a specified assessment time identifies the point at which participants are evaluated. Both are important for reproducibility. Here, the record states the assessment time and broad response categories, but does not report the detailed category thresholds, how missing assessments were handled, or whether outcomes were assessed by blinded reviewers. Masking is recorded as none, but the record does not describe further assessment safeguards.
The secondary outcomes concern hematologic response, relapse, clonal evolution, and survival following the regimen. Their names indicate what the investigators intended to assess, but the registry does not report numerical results for them in the registry record for this analysis. The time horizon and operational definitions for these secondary outcomes are not reported, so no additional survival or event-time method can be inferred.
Over-dispersion is a general concern when count data vary more than an assumed statistical model expects; a model that ignores it can understate uncertainty. That issue cannot be assessed from the record because the primary endpoint is described as categorical and no model or count distribution is reported. More generally, statistical methods should be matched to the outcome type and design, but a specific method should not be attributed to this study without a reported analysis plan or result.
10. Multiplicity, Missing Data and Analysis Populations
The registry names a primary outcome and secondary outcomes. The primary outcome is response rate at 6 months. Secondary outcomes include hematologic response, disease relapse, clonal evolution, and survival following fludarabine/cyclophosphamide. The record does not report a multiplicity strategy for interpreting several outcomes, such as a hierarchy, adjustment, or designation of exploratory analyses. It also does not report a statistical analysis plan describing how results across outcomes were to be handled.
In general, when many outcomes or tests are examined, the chance of at least one apparently notable finding can increase. A prespecified strategy can clarify which comparisons are confirmatory and how uncertainty should be interpreted. Without a reported strategy, no adjustment or formal error-control claim should be assumed. Since no outcome analyses are reported in the registry record, there are no posted tests or estimates for which a multiplicity adjustment can be evaluated.
Missing-data handling is not reported in the registry record. The entry does not say how an absent 6-month assessment, incomplete blood counts, withdrawal, or other unavailable outcome information would be treated. It does not report imputation, a complete-case approach, or sensitivity analyses. These methods should not be inferred from the endpoint description alone.
The primary outcome population is described as the 1 participant enrolled, but the registry does not provide further analysis-population definitions, such as criteria for inclusion in an efficacy or safety analysis. It does not report whether all enrolled participants were analyzed according to an intention-to-treat principle or another population definition. In general, clarity about analysis populations and missing outcomes helps readers judge how observed data relate to the intended question. Here, those details are unavailable, and the primary response result itself is not reported.
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 |
|---|---|---|---|
| Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia | 0 of 1 |
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 |
|---|---|
| Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia | 0 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Fludarabine/Cyclophosphamide in Participants With Severe Aplastic Anemia |
|---|---|---|
| infection | Infections and infestations | 1 of 1 |
| neutropenic fever | Infections and infestations | 1 of 1 |
Serious events with the highest arm-level rate: infection (100.0%), neutropenic fever (100.0%).
The registry lists 1 participant at risk for serious adverse events and 1 participant affected in the Fludarabine/Cyclophosphamide group. For other adverse events, it lists 1 participant at risk and 0 affected. The death count is 0. These are registry fields; the entry does not provide event-level timing, duration, severity grading, or attribution to study treatment.
The listed top serious adverse event terms are infection and neutropenic fever, each reported as 100.0%. The registry does not explain the denominator or how these term percentages relate to the serious-event participant fields. They should not be read as additional participants or as proof that the terms occurred independently; the same participant could be represented across more than one term. The record also does not provide detailed case descriptions or a breakdown of seriousness criteria.
In general, adverse event counts describe reported events within a defined observation and reporting framework; they do not alone establish causation. The registry entry does not report enough detail to assess event timing, exposure duration, or whether investigators considered events related to the regimen. With the small enrollment and limited event detail, the fields offer only a narrow description of recorded safety information, not a complete estimate of risk or a comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record shows that a phase 1/2, single-group pilot study of fludarabine plus cyclophosphamide was completed and that 1 participant was enrolled. It defines a primary hematologic response assessment at 6 months and identifies complete, partial, and no response as the possible categories. The primary response result is not reported in the registry record, so the posted information does not establish which category was observed.
The study also has no concurrent comparator. In general, an outcome observed in a treated group is not equivalent to a treatment effect: a treatment effect is a contrast with an outcome under another condition. This record cannot make that contrast. The study's pilot and phase 1/2 labels identify its registry classification but do not remedy the lack of a reported primary result or a control group.
The safety fields report serious adverse event counts, other adverse event counts, death count, and two serious event terms with percentages. They are limited registry entries, not a complete account of event characteristics or treatment attribution. They do not support a comparative safety conclusion.
The listed sample-size material is described as a planning illustration based on an observed effect and specified hypothetical assumptions. Such illustrations are not observed power and do not provide evidence that a treatment effect was detected. The registry does not report the trial's own sample-size justification or statistical analysis plan.
Accordingly, the record supports a description of the intended question, design, intervention, and limited safety entries. It does not support a numerical claim about hematologic response, a conclusion about comparative benefit or harm, or a claim that the regimen was effective or ineffective. The absence of a reported result is an information limitation, not evidence that a particular response did or did not occur.
13. Why This Trial Matters Statistically
This trial matters statistically because its design and reporting illustrate the difference between asking a clinical question and having enough reported information to answer it. The registry defines a 6-month hematologic response endpoint for refractory severe aplastic anemia and describes the regimen being studied. Yet it does not report the response category or count. A clearly named endpoint cannot substitute for the result needed to estimate an outcome.
The single-group design also shapes the scope of inference. In general, a one-group study can document outcomes in participants receiving an intervention, but a comparator is needed to estimate how those outcomes differ from an alternative. That distinction is especially important when interpreting pilot research: descriptive observations can motivate further study, but they do not establish a comparative treatment effect.
The enrollment entry is 1, which makes the reporting of the individual outcome especially consequential for understanding the study. The registry does not give that primary outcome result, response criteria in detail, or precision measures. Thus, neither the magnitude nor uncertainty of the primary response can be assessed from the record.
The registry's safety fields also show why event counts need context. Counts and term percentages are not a full safety analysis without definitions, observation details, and attribution. In general, statistical interpretation depends on knowing who was analyzed, how outcomes were measured, and how unavailable observations were handled; several such details are not reported in the registry record.
The planning illustrations provide a separate teaching point: hypothetical sample-size calculations depend on assumptions and do not describe the evidence generated by a completed study. They should not be mistaken for observed power. Overall, this record is useful for examining how design, endpoint reporting, and missing analysis details constrain inference, even when the clinical question and intervention are plainly identified.
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 trial-specific limitation is the single-group design. With no separate comparator, the record cannot support a direct estimate of how outcomes differ from another treatment or condition. Allocation is listed as NA and masking as none. The registry does not describe additional measures to reduce assessment bias.
Enrollment was 1. The primary outcome is described, but the result at 6 months is not reported. The registry also does not give detailed criteria for complete or partial response, or the method used to classify blood-count results. This prevents assessment of the outcome definition and leaves the intended response question unanswered in the posted results.
The registry does not report a statistical analysis plan, sample-size justification, interim analyses, analysis-population definitions, missing-data procedures, or outcome estimates with precision measures. It lists secondary outcomes but does not provide their numerical results or sufficient detail to interpret their timing and definitions. The entry does not explain whether adverse event terms refer to separate events or how their percentages were calculated.
Safety information is limited to the listed participant counts, death count, and serious adverse event terms. The record does not report duration of observation, event timing, severity grades, or attribution. These limitations prevent a comprehensive interpretation of safety information and preclude a comparative assessment.
These are limitations of what the registry record reports; they do not establish what information may exist outside the entry. The posted record alone supports only a narrow description of the design, intended endpoint, enrollment, and recorded safety fields.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia — NCT01187017.
- Registry record last updated 2021-07-02; status last verified 2016-02.
- Results first posted 2016-03-02.
- 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
NCT01187017 is a completed phase 1/2, single-group pilot study titled A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia. The study start is 2010-08, and primary completion is 2012-07. Enrollment is recorded as 1. Allocation is listed as NA, and masking as none.
The intervention is fludarabine at 125 mg/m squared plus cyclophosphamide at 60 mg/kg. The primary endpoint is hematologic response at 6 months, classified as complete, partial, or no response. The registry record does not report the primary response result or numerical results for the secondary outcomes.
Safety fields list 1 participant at risk and 1 affected for serious adverse events, 1 at risk and 0 affected for other adverse events, and 0 deaths. Infection and neutropenic fever are each listed as serious adverse event terms at 100.0%. The record does not report the statistical analysis plan, missing-data approach, or detailed response criteria.