A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (NCT00217594), a na phase 2 study. The primary outcome is Response to Treatment - Hematologic Improvement or Complete Response.

2. Clinical Question

3. Trial Design

This completed phase 2 study evaluated alemtuzumab in patients with myelodysplastic syndrome. The registry record lists an enrollment of 40 and a single-group model. Allocation is not applicable, and masking is none. These features identify the study as a treatment study without a concurrent control arm and without masking. They do not establish what other procedures, if any, were used to reduce bias.

The intervention description specifies a 1-mg intravenous test dose, followed the next day by 10 mg/dose intravenously for 10 days. The record lists alemtuzumab as the drug intervention. It gives no separate treatment arm against which to compare the intervention.

The registry record lists the study start as 2005-07-21, primary completion as 2017-02-06, and status as completed. The sponsor is the National Heart, Lung, and Blood Institute. These registry entries describe the study’s administrative record, but do not show when each participant was treated or followed.

The enrollment of 40 and the safety group of 31 are distinct figures in the record. Why those counts differ is not reported in the registry record. The number with evaluable primary endpoint data is also not reported in the registry record. No protocol rationale for the enrollment target, sample-size justification, or account of any changes to the study design is reported in the registry record. A single-group design can describe outcomes among participants receiving the intervention, but it does not by itself separate treatment effects from the natural course of disease, other care, or selection effects.

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: Out of 40 enrolled subjects, only 31 subjects were evaluable.

Overall 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.

6. Primary Endpoint

The registry lists the primary outcome as Response to Treatment - Hematologic Improvement or Complete Response, measured over 3 months.

The primary endpoint is the count of participants with hematologic improvement or complete response at 3 months after the first dose of alemtuzumab. The registry description says the criteria follow International Working Group definitions. Hematologic improvement concerns responses in the erythroid, platelet, and neutrophil lineages among patients with abnormal pretreatment values. The listed criteria include anemia or red-cell transfusion dependence, low platelet count or platelet-transfusion dependence, and low absolute neutrophil count.

Complete response is described using bone marrow and blood-count criteria. The registry definition includes less than 5% marrow blasts without evidence of dysplasia, along with normalization of peripheral blood counts. The specified count thresholds include hemoglobin of 110 g/L (11 g/dL) or more for patients not receiving erythropoietin or transfusions, a neutrophil count of 1.5 × 10⁹/L or more, and a platelet count of 100 × 10⁹/L or more.

As a general statistical concept, a response endpoint can translate several clinical measurements into a participant-level classification. That makes the outcome countable, but the classification depends on applying the stated criteria consistently and having the relevant measurements available. The record gives the endpoint definition and timeframe, but the number of responders, the denominator used for analysis, and the handling of missing measurements are not reported in the registry record. The endpoint’s intended role is therefore clear; its observed result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level response: each participant either meets the stated response definition at the specified assessment time or does not. The registry describes the endpoint as a count of participants, rather than a continuous measurement such as a blood-cell value. In general, a binary endpoint can be summarized as a number of participants meeting the definition and the number assessed. Those quantities allow estimation of the response proportion and its uncertainty. The response count and analysis denominator are not reported in the registry record, so neither can be interpreted for this study.

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimate. For a response proportion, it would help show how much precision the observed data support, given the number of participants assessed and the analysis method. A narrow interval generally indicates greater precision than a wide interval, while neither interval width nor the point estimate resolves design limitations such as the lack of a comparison group. No confidence interval for the primary response endpoint is reported in the registry record.

A p-value, if calculated, would address how compatible the observed data are with a specified statistical null hypothesis under the assumptions of a test. It would not measure the size or clinical importance of a response, and it would not correct the lack of a control group. The registry record lists no analyses and does not report a p-value or a hypothesis test for the primary endpoint. It is therefore not appropriate to infer statistical significance or lack of significance.

Why does the endpoint definition matter?

The endpoint combines hematologic improvement or complete response under criteria attributed to the International Working Group. The improvement criteria refer to pretreatment abnormalities in different blood-cell lineages, while complete response includes marrow and peripheral blood requirements. This means that classification depends on both baseline status and follow-up measurements. In general, a combined endpoint may count participants who meet different component criteria under a common response label. Its interpretation depends on precisely how components are combined, whether overlap is possible, and how missing assessments are handled. Those operational details are not reported in the registry record beyond the endpoint description.

The timeframe is 3 months after the first dose. A fixed assessment time gives an outcome a defined point of reference. It does not indicate whether additional assessments occurred, whether responses were sustained, or how participants who did not complete the scheduled assessment were treated analytically. Such follow-up and analysis details are not reported in the registry record.

What can the single-group design estimate?

In general, a single-group study can describe observed outcomes in the people who received the intervention. It cannot directly estimate a treatment contrast against a concurrent control group because there is no such group. A numerical response proportion, if available, would therefore describe the study participants and assessment process; it would not alone identify the causal effect of alemtuzumab. The study lists allocation as not applicable, masking as none, and a single-group model. The registry record does not report a statistical adjustment plan or other method that would create a valid concurrent comparison.

The record includes a planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such a calculation is a general hypothetical planning exercise, not evidence that this study randomized participants or used a two-arm design. The study itself is listed as single group, and its own sample-size justification is not reported in the registry record. A planning illustration is not observed power and cannot substitute for the missing endpoint estimate or its uncertainty.

How should event counts be read?

For the safety outcomes, a count of affected participants differs from a count of individual events. One participant could experience more than one event; the registry’s labels describe participants affected. The listed serious adverse event terms have percentages, but the record does not provide event-level timing or a fuller account of how multiple occurrences were handled. In general, a safety proportion depends on the defined safety population, event definitions, observation period, and completeness of reporting. The listed safety group includes 31 participants at risk; the reason it does not match the enrollment figure is not reported in the registry record.

Statistical methods for the primary endpoint, including any model, confidence-interval method, missing-data procedure, or prespecified hypothesis, are not reported in the registry record. The absence of these details means that no analysis method can be attributed to the trial from this record. Statistical interpretation should therefore stay with the design and descriptive information that are actually recorded.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Alemtuzumab")
n      <- c(31)
events <- c(21)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Alemtuzumab  31  21  67.7  48.6  83.3  50.1  81.4  50.0  81.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure: response defined as hematologic improvement or complete response at 3 months. It lists no analyses. Whether the study protocol included additional outcomes, planned comparisons, or a hierarchy of hypotheses is not reported in the registry record. The number of registry outcome measures alone does not establish how many analyses were planned or performed.

Multiplicity arises when several hypotheses or outcomes are tested; with repeated testing, the chance of at least one apparently notable result can increase. As a general statistical practice, investigators may specify a primary endpoint, define a testing order, or adjust inference for multiple comparisons. Whether any such approach was prespecified or used for this study is not reported in the registry record. No inferential result is posted for the primary endpoint, so there is no reported set of tests whose multiplicity adjustment can be evaluated.

The number included in the primary endpoint analysis, the handling of missing outcome assessments, and the definition of analysis populations are not reported in the registry record. In general, missing outcome data can affect both the denominator and the interpretation of a response proportion. Analyses may use different assumptions about participants without an observed assessment; those assumptions can change the estimate and its uncertainty. No particular missing-data method should be attributed to this study.

The registry lists enrollment of 40 and a safety group of 31 at risk. These counts serve different roles in the record, and the primary endpoint denominator is not reported in the registry record. The reason for the difference is not reported in the registry record. Without the analysis population and disposition information, it is not possible to determine whether the endpoint result was based on all enrolled participants or a subset.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenic fever (9.7%), clostridium difficile diarrhea (6.5%), non-neutropenic fever (6.5%), bacterial pneumonia (3.2%), cellulitis (3.2%).

The registry lists 31 participants at risk in the alemtuzumab group. It records 15 participants affected by serious adverse events, 31 affected by other adverse events, and 0 deaths. These are participant counts in the registry’s safety record; they are not a comparison with an untreated or alternative-treatment group. The reason the safety group contains 31 participants while enrollment is 40 is not reported in the registry record.

The most frequently listed serious adverse event terms are neutropenic fever (9.7%), Clostridium difficile diarrhea (6.5%), non-neutropenic fever (6.5%), bacterial pneumonia (3.2%), cellulitis (3.2%), and shingles (3.2%). These percentages are reproduced as recorded. They describe the posted serious-event terms, not the total range of possible adverse effects, and the record does not establish that alemtuzumab caused each event. It also does not report event timing, duration, recurrence, or the full method used to assess causality.

As a general statistical distinction, participant counts and event counts are not interchangeable: one person may experience multiple events. The posted counts therefore should not be added to infer a number of unique participants, nor should the listed percentages be treated as a comparative risk estimate. The registry record does not report a control group, which prevents a direct between-group safety comparison.

13. What the Result Does, and Does Not, Mean

The registry record documents a phase 2, single-group study of alemtuzumab in patients with MDS and defines a primary response endpoint at 3 months after the first dose. It also provides a treatment schedule and a set of safety counts. These details establish what the study set out to evaluate and what safety information was posted.

The record does not report the number of participants who met the primary response definition, the denominator assessed, or an estimate of response with its uncertainty. It therefore does not show the magnitude or precision of the primary endpoint result. The absence of a posted endpoint result should not be read as either evidence of response or evidence of no response.

Even if a response count were available, the single-group design would limit causal interpretation. Outcomes among treated participants do not, on their own, show what would have occurred in comparable patients without the intervention or under another treatment. The design provides no concurrent treatment contrast, and the registry record does not report an alternative analysis that establishes one.

The safety counts describe participants affected in the recorded group. They do not determine whether events were caused by the intervention, and they cannot quantify risk relative to another treatment. The serious-event terms identify events recorded in the registry, but do not provide a complete account of their clinical course or a comparative safety estimate.

In general, a registry record is useful for examining study design, endpoint definitions, and posted results. For this study, the design and safety information are more fully described than the primary efficacy outcome. The registry record does not report the statistical plan, endpoint analysis population, missing-data handling, or a sample-size justification. Conclusions should remain limited to the registry entries recorded: the study was completed, used a single-group design, specified a hematologic response endpoint, and posted descriptive safety counts. It does not provide enough information to quantify the primary response result or to establish a comparative treatment effect.

14. Why This Trial Matters Statistically

This study illustrates why a clearly stated endpoint and a reported endpoint result are both needed for statistical interpretation. The registry record defines hematologic improvement or complete response using specific marrow and blood-count criteria and gives the assessment time. That makes the intended outcome recognizable. However, without the number of participants meeting the definition and the denominator assessed, the endpoint cannot be quantified from the registry record.

It also illustrates the distinction between describing outcomes and estimating a comparative effect. A single-group study can record what happened among participants receiving an intervention, but there is no concurrent control arm to distinguish the intervention’s contribution from other explanations. A result from such a design needs to be interpreted according to that limitation, even when the endpoint criteria are detailed.

The difference between the enrollment count of 40 and the safety group of 31 at risk highlights the importance of population definitions. Enrollment, safety, and primary endpoint populations can differ, but the reasons for those specific counts and the primary endpoint denominator are not reported in the registry record. Clear participant accounting is needed to understand which observations contribute to each estimate.

Finally, the record shows why statistical transparency includes more than a named endpoint. Analysis methods, handling of missing assessments, multiplicity plans, and sample-size rationale affect how results should be read. Those details are not reported in the registry record. The study is therefore a useful example of how a record may describe the clinical question and safety observations while leaving the primary quantitative result and its statistical precision unavailable.

15. 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 primary limitation is that the registry record does not report the primary endpoint result. It gives the response definition and timeframe but no responder count, analysis denominator, estimate, confidence interval, or test result. As a result, the central efficacy outcome cannot be quantified from the record.

The single-group design has no concurrent comparator, and masking is listed as none. This limits causal interpretation and leaves open the possibility of bias in outcome assessment or other study processes. The record does not report whether any other procedures were used to address these concerns.

The enrollment is 40, whereas the safety group lists 31 participants at risk. The reason for the difference, the number assessed for the primary endpoint, and participant disposition are not reported in the registry record. Thus, it is not possible to connect the safety denominator to the endpoint population or to determine how incomplete follow-up may have affected the response assessment.

The endpoint combines hematologic improvement or complete response. The record describes criteria but does not report component-specific results, how overlapping categories were handled, or how missing measurements affected classification. It also does not report whether response was sustained beyond the stated assessment time.

The registry record does not report a statistical analysis plan, missing-data procedures, multiplicity approach, or sample-size justification. Safety details are also limited: serious adverse event counts and selected terms are posted, but event timing, duration, causality assessment, and a comparative safety estimate are not reported in the registry record. These gaps restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome — NCT00217594.
• Registry record last updated 2018-10-30; status last verified 2017-10-17.
• Results first posted 2018-09-24.
• 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.

19. Record Summary

The registry record describes a completed phase 2 study of alemtuzumab in myelodysplastic syndrome, with an enrollment of 40 and a single-group design. Participants received a 1-mg test dose followed by 10 mg/dose intravenously for 10 days. The primary endpoint was hematologic improvement or complete response at 3 months after the first dose, defined using International Working Group criteria.

The record lists a safety group of 31 participants at risk, 15 affected by serious adverse events, 31 affected by other adverse events, and 0 deaths. The primary response result, endpoint analysis denominator, and statistical analyses are not reported in the registry record. The lack of a comparator also limits interpretation of treatment effects and comparative safety.