Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer (NCT00074269), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The clinical rationale describes chemotherapy before donor-cell transplantation as an approach intended to suppress tumor growth and reduce rejection of donor cells. Donor cells may replace the recipient’s immune system and may contribute to a graft-versus-tumor effect; donor lymphocyte infusion is described as a way to increase that effect. The rationale also recognizes immune responses against normal cells and lists antithymocyte globulin, cyclosporine, and methotrexate as measures intended to limit them. These statements describe the study rationale, not findings from the five participants. The registry record does not report detailed response results, progression-free survival results, or overall survival results.

3. Trial Design

This was a phase II, single-group study of allogeneic peripheral blood progenitor cell transplantation in patients with metastatic breast cancer. The title identifies antithymocyte globulin, high-dose melphalan, and fludarabine as part of the treatment approach. Other interventions listed in the registry are filgrastim, graft-versus-tumor induction therapy, therapeutic allogeneic lymphocytes, cyclosporine, and methotrexate. The record does not give a detailed treatment schedule or explain which participants received each listed intervention at what time.

The design was not randomized: allocation is listed as not applicable, the model is single group, and masking is listed as none. There is no separate comparator arm in the registry record. Consequently, the trial does not make a like-for-like comparison between the transplant approach and another treatment. Any observed participant counts describe the treated group, rather than a contrast that isolates a treatment effect.

The registry records an enrollment of 5 and states that the study was closed early due to lack of accrual. Its status is terminated. The recorded study start is 2003-07 and the primary completion is 2008-03. The primary endpoint has a stated timeframe of 5 years post transplant. The record does not explain whether every participant completed that timeframe, how follow-up was handled after early closure, or what criteria determined termination beyond the stated lack of accrual.

Secondary outcomes include progression-free survival, overall survival, response as measured at 12 months post allografting, and frequency of induction of full donor chimerism of lymphocytes as measured at 1 month post allografting. The record lists 7 outcome measures overall, but does not provide analysis results for the secondary outcomes. It records no analyses. The protocol’s sample-size justification, interim analysis plan, and detailed statistical analysis plan are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: study was closed early due to lack of accrual.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: This is a pilot study. The original planned target accrual was 15 male or female patients age 18-60 but due to poor enrollment the study was closed to accrual early after 5 patients had been enrolled.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over 5 years post transplant.

The primary endpoint is the number of participants with adverse events, expressed as a participant count. Its stated assessment timeframe is 5 years post transplant. A participant-count endpoint records how many people experienced an event, rather than the total number of separate event episodes. It can give a basic description of the number of participants with reported adverse events during the stated period.

This kind of endpoint is used to describe safety experience in the treated group. It is not, by itself, a measure of whether the treatment caused an event. Without a comparison group, event counts cannot show how the frequency differs from what would have occurred under another treatment or in the absence of the study regimen. The registry record does not state an event definition, severity grading rules, attribution rules, or the method used to collect events.

The adverse-event results list 5 participants at risk for other adverse events, with 5 affected, and 5 at risk for serious adverse events, with 0 affected. The record also lists 3 deaths. These are distinct reported counts; they do not establish the cause, timing, or relationship of events or deaths to treatment. The registry does not report participant-level follow-up details or explain whether all participants were observed for the full stated timeframe. Accordingly, the counts describe the posted safety information but do not establish a complete event history for every participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching the method to the design and the information actually recorded. This study is identified as a single-group phase II trial, with allocation listed as not applicable and masking listed as none. There is no randomized comparison in the registry record. The central statistical task supported by the posted safety information is therefore descriptive: to state how many participants were recorded in each adverse-event category and how many deaths were listed, without assigning a comparative treatment effect.

What does a participant count describe?

A count of participants with an event tells how many people in the group met the recorded event criterion. It differs from an event count, which could include multiple events experienced by one person. For the primary endpoint, the registry specifies the number of participants with adverse events and names participants as the unit. The posted figures list 5 participants at risk for other adverse events and 5 affected, alongside 5 at risk for serious adverse events and 0 affected. The record does not provide individual event histories, event episode counts, or definitions sufficient to reconstruct the categorization.

For interpretation, the denominator matters: a count is meaningful in relation to the participants who were considered at risk or observed. Here, the record lists 5 at risk in each reported category. It does not say whether the same follow-up and ascertainment procedures applied to every participant, or whether every participant contributed the full 5 years post transplant. This uncertainty limits what the reported counts can say about the full intended timeframe.

Why is a single-group design different?

A comparative trial estimates a contrast between groups, whereas a single-group study describes outcomes in the one group enrolled. With no control group, the registry record offers no internal estimate of what event frequency or clinical course would have been under an alternative strategy. Any difference between an observed outcome and an external expectation would also be difficult to interpret without details about the external population and how it was selected. No such comparison is reported. General statistical reasoning therefore cautions against turning these participant counts into a causal claim.

Randomization, when used, helps make groups comparable on average, while masking can reduce certain measurement or reporting biases. This study is not randomized and has no masking recorded. Those design features do not invalidate the descriptive counts, but they restrict the kinds of inference the design can support. The registry record does not explain whether event assessment was standardized or independently reviewed.

What would uncertainty measures add?

A confidence interval is a statistical range intended to express uncertainty around an estimate under a specified method and assumptions. It does not guarantee that the true value lies in the interval, and it does not resolve limitations such as missing follow-up, outcome misclassification, or lack of a comparator. No confidence intervals or other uncertainty estimates are reported for the posted outcomes. With such a small enrolled group, any estimate of event frequency would be inherently unstable; this is a general statistical explanation, not a new calculation for this study.

A p-value assesses compatibility between data and a specified statistical model or null hypothesis. It is not a measure of clinical importance and cannot, on its own, establish causation. The registry record provides no p-values and reports no analyses. Therefore, there is no inferential test result to interpret for the primary safety endpoint or the listed secondary outcomes.

How should survival outcomes be approached?

Progression-free survival and overall survival are time-to-event outcomes. Such analyses generally use both the event information and the length of observed follow-up, with explicit handling of participants whose event has not been observed by the end of follow-up. A survival estimate can be affected by censoring, which means a participant’s event time is not observed within the available follow-up. These are general concepts. The registry record does not report survival estimates, event counts for these outcomes, censoring details, or the analysis method, so no survival curve or survival contrast can be interpreted from this record.

The listed response assessment at 12 months post allografting and donor chimerism assessment at 1 month post allografting also require defined criteria, denominators, and handling of participants without an assessment. Those details and results are not reported in the registry record. The endpoint titles alone do not show how many participants were assessed or how outcomes were classified.

What does the record say about planning and analysis?

The registry records 7 outcome measures and no analyses. It does not report a protocol-based sample-size justification, interim monitoring approach, or detailed statistical plan. A sample-size calculation is a planning exercise that depends on a target effect, variability or event assumptions, significance level, power, and design. A planning illustration is not evidence that a study achieved a particular power, and it does not replace an observed estimate or an uncertainty interval. The registry’s record does not permit a conclusion about the original design assumptions or whether the enrollment of 5 met a planned target.

Multiplicity arises when several outcomes or statistical tests are considered. Without a reported analysis plan, it is unknown whether any adjustment or outcome hierarchy was intended. Since the record lists no analysis results, there are no reported tests to evaluate for multiplicity. In general, when many outcomes are assessed, interpreting isolated findings without knowing the prespecified plan can overstate the strength of evidence. That general concern does not imply that a particular unreported result exists.

Missing-data methods are also important. A registry may list an endpoint timeframe without specifying how incomplete observation, missed assessments, or early discontinuation were handled. Here, the study was closed early due to lack of accrual, but the record does not state how early closure affected follow-up or which participants contributed to each outcome. No analysis population definitions are reported. As a result, the posted counts should be read as the recorded results, not as evidence that all planned assessments were complete or that a particular missing-data method was used.

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("Treatment")
n      <- c(5)
events <- c(5)
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  Treatment  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary count of participants with adverse events and secondary outcomes for progression-free survival, overall survival, response at 12 months post allografting, and full donor chimerism at 1 month post allografting. The record does not identify a formal hierarchy among the secondary outcomes or describe adjustment for multiple testing. It also reports no analyses. Therefore, there are no inferential findings in the record for which the effect of multiplicity adjustment can be evaluated.

In general, assessing several endpoints can increase the chance of seeing an apparently notable result by chance if each is tested separately. Prespecifying a primary outcome and an analysis strategy can help clarify which findings are confirmatory and which are exploratory. The registry identifies a primary endpoint, but the full statistical plan and any multiplicity procedures are not reported in the registry record. The listed outcome titles alone do not reveal whether all were prespecified in the same way or how they were intended to be interpreted.

The record states that the study was closed early due to lack of accrual. It does not describe missing-data rules, the completeness of follow-up, or the analysis populations used for any endpoint. In general, missing or incomplete observations can affect both the denominator and interpretation of an outcome. For the primary endpoint, the safety figures list 5 participants at risk in each category, but the record does not specify whether all participants had equivalent observation through the stated 5 years post transplant. It would be speculative to assume a particular censoring, imputation, or exclusion method.

The registry reports no interim analysis plan, early stopping boundary, or detailed analysis strategy. Early closure is attributed to lack of accrual, not to a stated statistical stopping rule. No further explanation of the decision or its statistical implications is reported.

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 non-serious adverse event terms

The safety figures list 5 participants at risk for serious adverse events, with 0 affected, and 5 participants at risk for other adverse events, with 5 affected. The record also lists 3 deaths. These are participant-level counts as recorded; they do not identify how many separate events occurred or which participants experienced more than one event. The registry does not provide the specific adverse-event terms, event dates, severity details beyond the serious category, or attribution to treatment.

The number of deaths should not be interpreted as a treatment-related death count. Cause and timing of death are not reported in the registry record, and the record does not explain the relationship, if any, between deaths and adverse events. The absence of participants in the serious adverse-event category does not establish absence of all serious harms, particularly without definitions and follow-up details. Likewise, the count of participants with other adverse events does not show whether those events were mild, clinically important, expected, or caused by the regimen.

The endpoint timeframe is stated as 5 years post transplant, but completeness of observation over that timeframe is not described. These results are descriptive safety information from the enrolled group, not a comparative safety estimate.

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

The posted record supports a limited description of safety observations in a small group treated in a single-group phase II study. It reports an enrollment of 5, 0 participants affected by serious adverse events, 5 affected by other adverse events, and 3 deaths. The study closed early due to lack of accrual and is listed as terminated. These registry entries characterize the registry’s recorded information; they do not establish why any participant experienced an event or died.

The record does not provide a control group, so it cannot estimate how the outcomes compare with another treatment or with a different clinical course. It also does not report inferential analyses, confidence intervals, p-values, or adjusted treatment effects. The event counts should not be treated as proof that the regimen caused or prevented an outcome. Nor should the absence of a serious adverse event in the posted count be read as proof that the approach is free of serious risks.

The study’s stated purpose concerns a transplant approach for metastatic breast cancer, but the posted results described in the registry do not include response, progression-free survival, or overall survival findings. Those outcomes are listed, but their results are not reported in the registry record. Thus, the available information does not establish whether the regimen affected tumor response or survival. Likewise, donor chimerism is listed as an outcome without a reported result.

In general, statistical evidence is more informative when outcome definitions, complete follow-up, analysis methods, and uncertainty estimates are available. Their absence does not mean that a result was favorable or unfavorable; it means that the registry record does not make that result available for interpretation. The narrow conclusion is that a small, early-closed, single-group study has these posted safety counts, while key details needed to assess completeness, attribution, and clinical outcomes are not reported.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clinical rationale and evidence that can be interpreted from posted results. The rationale describes a potential graft-versus-tumor effect and measures intended to limit immune responses against normal cells. Those mechanisms motivated the intervention, but the registry’s reported counts do not test whether those mechanisms produced clinical benefit. The trial’s listed secondary outcomes include response, progression-free survival, overall survival, and donor chimerism, yet corresponding results are not reported in the registry record.

It also shows why design determines the scope of statistical conclusions. A single-group study can describe what was recorded among participants, but it cannot make a randomized treatment comparison. In this case, the enrollment was 5 and the study closed early because of lack of accrual. Even a carefully reported event count in a small group does not, by itself, identify the cause of events or quantify how outcomes would differ under another approach.

The record also highlights the value of complete outcome reporting. A named endpoint and a stated timeframe do not reveal the event definitions, observation completeness, handling of missing assessments, or analysis population. Such details matter for evaluating what a count represents. Likewise, listing several secondary outcomes without their results leaves questions about clinical outcomes unanswered.

Statistically, the available evidence is descriptive and limited. No analyses are reported, and there are no uncertainty estimates with which to judge the precision of an effect. Recognizing these limits is important: the counts remain useful as a record of what was posted, but they should not be expanded into claims about comparative safety, efficacy, or causal effects.

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 registry record gives little detail about the conduct and analysis of this study. Although the primary endpoint is a count of participants with adverse events and the timeframe is 5 years post transplant, event definitions, grading criteria, attribution procedures, and collection methods are not reported. The record does not describe whether follow-up was complete for all participants or how time outside observation was handled.

The single-group design has no concurrent comparator, and the record lists no masking. Those features limit causal and comparative interpretation. The small recorded enrollment of 5 and closure due to lack of accrual further constrain how broadly the descriptive experience can be interpreted. The record does not report why accrual was limited, the planned enrollment target, or a protocol-based sample-size justification.

Deaths are listed, but their causes, timing, and relationship to treatment are not reported. Specific adverse-event terms and event episode counts are also absent. The reported serious and other adverse-event categories therefore do not provide a detailed clinical account of harms.

Although secondary outcomes include response, progression-free survival, overall survival, and donor chimerism, results for them are not reported in the registry record. No analyses, confidence intervals, p-values, analysis populations, missing-data procedures, interim analysis plan, or full statistical plan are reported. The record also does not explain how early closure affected planned assessments or follow-up. These gaps limit conclusions to the posted descriptive counts and prevent assessment of the precision or completeness of other outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer — NCT00074269.
• Registry record last updated 2023-06-05; status last verified 2023-05.
• Results first posted 2014-11-24.
• 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

NCT00074269 is a phase II, single-group study of allogeneic peripheral blood progenitor cell transplantation for metastatic breast cancer. The registry lists antithymocyte globulin, high-dose melphalan, and fludarabine among the treatment components, with additional biological and drug interventions. Allocation is not applicable, masking is none, and no comparator group is recorded.

The study enrolled 5 participants, closed early due to lack of accrual, and is listed as terminated. Its primary endpoint is the number of participants with adverse events, with a timeframe of 5 years post transplant. The posted safety figures list 0 of 5 participants with serious adverse events, 5 of 5 with other adverse events, and 3 deaths. The record does not report event details, causes of death, or comparative analyses.

Secondary outcomes include survival, response, and donor chimerism, but their results are not reported in the registry record. No analyses or detailed statistical plan are listed.