Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer (NCT02995330), a na phase 1 study. The primary outcome is Prostate-specific Antigen (PSA) Response.

2. Clinical Question

The study asks whether a six-month biochemical PSA response was observed after sex-mismatched allogeneic bone marrow transplantation followed by Cytoxan and testosterone in men with progressive metastatic castration-resistant prostate cancer. The registry describes a pilot study and lists no comparison group. Its primary outcome is the percentage of participants meeting a PSA threshold at six months after transplant.

This question concerns an outcome measured after treatment in a small, uncontrolled pilot study. The registry record does not provide an estimate of the response percentage, participant-level PSA values, or a confidence interval. Consequently, the listed endpoint establishes what the study intended to assess, but not what the observed response was or how precisely it was estimated.

3. Trial Design

The registry identifies this as a phase 1 pilot study of sex-mismatched allogeneic bone marrow transplantation for men with metastatic castration-resistant prostate cancer. The study is single-group, has no masking, and lists allocation as NA. Enrollment is recorded as 3. These features describe a small treatment study without a concurrent control group, rather than a randomized comparison.

The registry describes eligible participants as men with progressive metastatic castration-resistant prostate cancer after first-line androgen deprivation therapy alone or androgen deprivation therapy plus docetaxel. Participants were to have an identified related female donor, such as a mother, sister, daughter, or second-degree relative. The listed intervention combines bone marrow transplantation with Cytoxan and testosterone. The arm description mentions a standard non-myeloablative conditioning regimen and infusion of non-T-cell-depleted bone marrow from a related female donor. The available arm description is truncated, so further treatment details are not reported in the registry record.

The primary outcome is prostate-specific antigen response, expressed as a percentage of participants and assessed at six months. The specified endpoint is complete biochemical response, using different PSA thresholds for participants post-prostatectomy and participants post-radiation therapy. Other listed outcomes include transplant-related mortality, PSA decline, objective response, progression measures, graft-versus-host disease, and donor chimerism. The registry lists 12 outcome measures, but the outcome results are not reported in the registry record.

The study is marked terminated. The registry record gives a start date of 2017-02-09 and a primary completion date of 2021-06-16. It does not report why the study was terminated, whether the planned enrollment differed from the recorded enrollment, or whether the study ended as originally intended. The statistical analysis plan and any sample-size justification 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

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 Prostate-specific Antigen (PSA) Response, measured over 6 months.

The primary endpoint is the percentage of participants with a complete biochemical response at six months after transplant. The registry defines response as PSA <0.1 ng/mL for participants post-prostatectomy and PSA < 1 ng/mL for participants post-radiation therapy. This is a binary outcome at the participant level: each participant either meets the applicable threshold or does not, and the percentage describes the share meeting it.

PSA is a biomarker used in prostate cancer monitoring. In general, a threshold-based endpoint translates a measured value into a stated response criterion that can be counted consistently. The distinct thresholds in this study reflect the two post-treatment settings named in the registry definition; the record does not provide further rationale for the cutoffs or describe how participants in each setting were distributed.

A six-month endpoint gives a defined assessment time, but it does not by itself describe the timing or durability of a response beyond that assessment. The record does not report individual PSA measurements, the number meeting either threshold, an estimated response percentage, or uncertainty around an estimate. It therefore identifies the intended measure without showing the observed endpoint result. The relationship between this biochemical response and other outcomes in the study is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design determines what comparisons are possible. This trial is registered as single-group, with allocation listed as NA and masking listed as none. In general, a single-group study describes outcomes in participants who receive the intervention; it does not create a randomized control group. Random allocation can help balance known and unknown participant characteristics between groups, while a concurrent comparator can show how outcomes differ under another condition. Neither feature is listed for this study. As a result, an observed change or response, if reported, would be descriptive of this group and would not by itself establish a causal treatment effect.

What does a percentage endpoint represent?

The primary outcome is a percentage of participants with a complete biochemical response at six months. In general, a binary endpoint classifies each participant according to whether a prespecified condition is met, then describes the number meeting it relative to the number assessed. The registry specifies the condition using PSA thresholds that differ according to whether a participant had prostatectomy or radiation therapy. It does not report the response count, the number assessed at the endpoint, or the estimated percentage. No calculation of that percentage can therefore be made from the registry record.

For a binary endpoint, an uncertainty interval can indicate how much sampling variation is compatible with an estimated response rate. In general, a confidence interval is not a guarantee that the true value lies in the interval; it summarizes uncertainty under a statistical model and method. With enrollment recorded as 3, any estimate based on the full group would be highly sensitive to individual outcomes. The registry does not report a confidence interval, the interval method, or any other precision measure.

Why does over-dispersion matter?

In general, a statistical model for binary outcomes often assumes that outcomes vary according to a specified probability structure. Over-dispersion means the observed variability is greater than that structure would predict. If a method ignores over-dispersion when it is present, uncertainty can be understated. This concept is relevant when interpreting estimates from group-level or repeated data, but the registry does not report a model, a dispersion estimate, or a test for over-dispersion. It is not possible to say whether over-dispersion was assessed or whether it would apply to the primary endpoint analysis.

What is known about the statistical analysis?

The registry lists zero analysis entries. It does not report the statistical methods used for the primary or secondary outcomes, the analysis population, the handling of missing data, or the calculation of uncertainty. The statistical plan, any adjustment for covariates, and any interim analyses are not reported in the registry record. No particular method should be assumed from the outcome definitions alone.

The study lists several secondary outcome types. In general, an analysis of multiple outcomes raises a multiplicity question: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Possible approaches include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary findings as exploratory. The registry identifies a primary endpoint and lists secondary outcomes, but it does not report whether multiplicity was addressed or how secondary results were interpreted.

How should planning illustrations be read?

The planning assumptions associated with sample-size illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations describe planning for a stated fraction of an observed effect. Time-to-event illustrations use a total event count; other illustrations use participants per arm. These are planning assumptions, not a description of the registered single-group design. In particular, an equal-allocation, two-arm calculation does not turn this study into a controlled comparison.

In general, sample-size calculations estimate the amount of information a future design might need under chosen assumptions. They depend on the effect size, variability, analysis method, and target power. They are not observed power, do not establish the chance that a treatment is effective, and cannot substitute for reported results. Here, the registry record does not report the observed primary effect or the analysis from which a planning illustration could be interpreted. The study's own design justification is not reported in the registry record.

Time-to-event outcomes such as time to PSA progression and time to clinical or radiographic progression require information about event timing and follow-up. In general, censoring occurs when a participant's event time is not observed during the available follow-up; suitable methods account for that incomplete timing. The registry lists these outcomes but does not report event counts, follow-up distributions, censoring details, estimates, or analysis methods. No conclusion about progression can be drawn from the outcome titles alone.

Finally, statistical interpretation depends on the population included in each analysis and whether observations are missing. The registry does not report whether all enrolled participants contributed to each endpoint, how missing assessments were handled, or whether analyses followed a prespecified population definition. These omissions prevent reconstruction of the analysis and assessment of the robustness of any result. Since no analysis entries or endpoint values are reported, there is no posted estimate to recalculate.

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("Bone Marrow Transplantation")
n      <- c(3)
events <- c(0)
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  Bone Marrow Transplantation  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PSA response endpoint and multiple secondary outcomes, including PSA decline, objective response, progression, transplant-related mortality, graft-versus-host disease, and donor chimerism. It reports 12 outcome measures but zero analysis entries. No results are reported for the primary or secondary measures, and the record does not describe whether multiplicity was addressed.

In general, testing several outcomes can increase the chance of finding at least one result that appears noteworthy by chance. A statistical plan may address this through adjustment, a hierarchy of outcomes, or by explicitly treating secondary analyses as exploratory. Which, if any, approach was used is not reported in the registry record. The outcome list alone does not establish that every endpoint was analyzed or that any particular result was confirmatory.

The record does not report missing-data counts, endpoint-specific denominators, reasons for missing assessments, imputation methods, or sensitivity analyses. It also does not identify the analysis population for the primary endpoint or secondary outcomes. These details matter because an estimate may depend on which participants were assessed and how unavailable measurements are handled. Enrollment of 3 does not establish that all participants had an evaluable six-month PSA result.

In general, an analysis population definition states which participants contribute to a given analysis, while a missing-data method states how unavailable measurements are treated. Without those definitions and the underlying outcome counts, the observed analysis cannot be reconstructed or checked for sensitivity to missing observations. The registry record does not report whether analysis choices were prespecified, changed, or applied consistently across outcomes.

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.

The registry records 0 serious adverse events among 3 participants at risk in the bone marrow transplantation group. It also records 0 other adverse events among 3 participants at risk and 0 deaths. No top serious adverse-event terms are listed. These are recorded counts for the group described in the registry; they are not estimates of a risk-free treatment.

A zero count in a small group does not establish that an event cannot occur or that its underlying risk is zero. In general, the precision of safety estimates depends on the amount of observed information, and a small study can miss uncommon events. The registry does not report event definitions, event-level details, exposure time, follow-up duration for safety, or methods used to collect adverse events. The figures should therefore be read as the counts recorded, not as comprehensive evidence about safety.

The registry lists transplant-related mortality and graft-versus-host disease among secondary outcomes, but outcome results for those measures are not reported in the registry record. The adverse-event counts do not provide results for every named safety outcome. The reason the study was terminated is also not reported, so the status cannot be interpreted as evidence of a safety-related stopping decision.

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

The registry record establishes that a phase 1 pilot study was registered to assess sex-mismatched allogeneic bone marrow transplantation followed by Cytoxan and testosterone in men with metastatic castration-resistant prostate cancer. It specifies a six-month PSA response endpoint and several secondary outcomes. It does not report the primary response result, secondary outcome results, or statistical analyses. Accordingly, the posted record does not provide an estimate of how often the primary response occurred.

The study is single-group and has no listed comparator arm. In general, observations from a single group can describe what happened to participants receiving the study regimen, but a comparison with another group is needed to estimate how outcomes differ between treatment strategies. Even if an outcome were reported, the design would limit conclusions about whether the intervention caused it. The available record contains no outcome value from which to make even a descriptive estimate.

The enrollment recorded as 3 also limits the amount of information that could be obtained about outcomes and their precision. The registry does not report an uncertainty interval for the primary endpoint or any other precision measure. It is therefore not possible to judge the range of response values compatible with the observed data or to assess how stable an estimate might be.

The recorded safety counts are 0 serious adverse events, 0 other adverse events, and 0 deaths among 3 at risk. These counts describe the registry entry and do not prove that the intervention has no safety risks. The record does not give event-level details or the reason for termination, and it does not report results for the named transplant-related mortality or graft-versus-host disease outcomes.

These limits do not make the registry record uninformative: it identifies the intended population, regimen, study structure, endpoint definition, and recorded safety counts. They do mean that the record cannot support a conclusion about treatment benefit, comparative effectiveness, or the full safety profile. The distinction between a planned measurement and a reported result is essential to a careful reading.

14. Why This Trial Matters Statistically

This study illustrates why design information and outcome information need to be read separately. The registry defines a clinically specific question, an intervention, and a six-month PSA threshold, but does not report the resulting endpoint value. Knowing what an outcome was intended to measure cannot answer what the study observed. Statistical interpretation begins with the actual estimates and their denominators; those are absent from the registry record.

The single-group design is also statistically important. Without a concurrent comparator, the study can describe outcomes within the treated group if they are reported, but it cannot directly estimate a difference between treatment strategies. The allocation entry of NA and the absence of masking are consistent with the registered single-group structure. A causal comparison should not be inferred from the intervention and endpoint descriptions.

The small recorded enrollment makes precision especially important. A percentage from a small study can change substantially when an individual participant's outcome changes. Confidence intervals and transparent outcome counts help readers assess that uncertainty. Neither an endpoint estimate nor an interval is reported in the registry record, so its precision cannot be evaluated.

The case also highlights the difference between a trial's listed outcomes and its analyzed outcomes. The registry names 12 outcome measures and zero analysis entries. Without posted results, analysis methods, missing-data handling, or analysis populations, readers cannot assess consistency across endpoints or determine whether findings were robust. Likewise, the status of terminated does not reveal why the study ended.

For biostatistical interpretation, the key lesson is that design, measurement, analysis, and reporting each contribute distinct information. Here, the design and intended measures can be described, but the results needed for statistical inference are not reported. Preserving that distinction avoids turning an endpoint definition or a zero event count into a stronger claim than the registry supports.

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.

Several limitations specific to this record constrain interpretation. The study is registered as a single-group phase 1 pilot study, with no comparator and no masking. Its recorded enrollment is 3. These design features limit direct comparative inference and the amount of information available to characterize outcome frequency or precision.

The primary endpoint is defined, but its result is not reported. The registry does not give the number of participants meeting the PSA thresholds, endpoint-specific denominators, individual PSA values, or an uncertainty interval. It also does not report results for the named secondary outcomes. As a result, no response estimate or assessment of progression, objective response, transplant-related mortality, graft-versus-host disease, or donor chimerism can be made from this record.

The intervention description is incomplete. It identifies bone marrow transplantation followed by Cytoxan and testosterone and mentions conditioning and donor marrow infusion, but the arm description is truncated. Further regimen details are not reported in the registry record. The reason for termination is also not reported, so the status cannot be linked to a particular operational or clinical explanation.

There is no reported statistical analysis plan, analysis population, missing-data approach, multiplicity method, or interim analysis information. The registry lists zero analysis entries. Without these details and the underlying outcome data, the reported analyses cannot be reproduced or evaluated for sensitivity. Any unreported protocol rationale or design decision should not be inferred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer — NCT02995330.
• Registry record last updated 2024-02-13; status last verified 2024-02.
• Results first posted 2024-02-13.
• 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 NCT02995330, a phase 1 pilot study of sex-mismatched allogeneic bone marrow transplantation for men with metastatic castration-resistant prostate cancer. It is listed as single-group, with no masking and allocation recorded as NA. Enrollment is 3, and the study status is terminated.

The primary outcome is the percentage of participants with complete biochemical PSA response at six months, using thresholds of PSA <0.1 ng/mL post-prostatectomy and PSA < 1 ng/mL post-radiation therapy. The record lists 12 outcome measures but zero analysis entries. The primary endpoint result and secondary outcome results are not reported in the registry record.

The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths among 3 participants at risk. These counts do not establish an absence of risk. The statistical analysis plan, missing-data methods, analysis populations, and reason for termination are not reported in the registry record.