CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation for T and B Cell Depletion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation for T and B Cell Depletion (NCT00579124), a non-randomized phase 2 study. The primary outcome is Number of Participants With Successful Engraftment.

2. Clinical Question

The study is described as a pilot evaluation of engraftment and graft-versus-host disease (GVHD) after transplantation using depleted grafts. Its stated feasibility focus also includes treatment-related mortality, with specific attention to interstitial pneumonitis, and severe GVHD. These aims describe what the study sought to evaluate; they are not evidence that any outcome occurred at a particular rate.

The donor-match strata matter when interpreting the question. Stratum 1 covers fully matched donors and specified mismatches, while Stratum 2 covers haploidentical matches and specified mismatches that include DRB1. Because allocation was non-randomized and the strata represent different matching categories, a simple comparison between their outcomes would mix treatment experience with differences in donor matching and potentially other factors. The registry record does not report an adjusted comparison or a causal treatment-effect estimate.

3. Trial Design

This was a Phase 2, non-randomized, parallel study listed as completed. The registry record lists enrollment of 93 and Children's Hospital of Philadelphia as the sponsor. The recorded start is 2005-01, and the primary completion date is 2017-01-15. The intervention is the CliniMACs device, described as being used to deplete CD3+ and CD19+ cells from peripheral stem cell grafts.

The study has two strata based on donor matching. Stratum 1 includes 6/6 or 8/8 matched donors, donors with 1 antigen or allele mismatch at A or B or DRB1, and a specified 2-antigen or allele mismatch pattern involving A and B but not DRB1. The description says grafts in this stratum undergo CD3+ and CD19+ depletion. The rest of that arm description is truncated in the registry record, so further details are not reported in the registry record.

Stratum 2 includes haploidentical matches and specified 2-antigen and/or allele mismatches where one mismatch includes DRB1. Its description specifies CD3+ and CD19+ depletion and no T-cell add back. The registry record does not report random assignment, and masking is listed as none. It does not describe a separate untreated or standard-treatment control arm.

The strata therefore provide descriptions of patient groups receiving the intervention under different donor-match conditions, not randomized treatment groups. A comparison between these groups would not isolate the effect of depletion: donor matching differs by design, and the registry record does not report methods to adjust for such differences. The enrollment field gives an overall figure, while the safety summaries report stratum-specific participants at risk. Detailed eligibility criteria, recruitment flow, baseline characteristics, treatment deviations, and follow-up completeness 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 Number of Participants With Successful Engraftment, measured over 100 days Post Transplant.

The primary endpoint is the number of participants with successful engraftment, assessed at 100 days post transplant. The registry defines success by whether a participant achieved an absolute neutrophil count (ANC) >500 and platelet count >20 x 109/l by that time. This is a binary outcome at the participant level: each participant either meets the stated definition or does not, based on the recorded counts and timing.

Engraftment is used in transplantation studies as an indicator that transplanted blood-forming cells have established the specified blood-cell production milestones. A threshold-based endpoint turns laboratory measurements into a prespecified clinical classification, which can be summarized as a count of participants meeting the definition. The specified time point also makes clear when the criteria are to be assessed; outcomes outside that time point are not interchangeable with this endpoint.

The registry record does not report how many participants met the definition, the denominator used for the primary analysis, or whether all participants had measurements available at the stated time. It also does not report an estimated proportion, confidence interval, hypothesis test, or analysis population for this endpoint. Consequently, the endpoint definition can be described, but the registry record does not establish the observed level of engraftment or the precision of an estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a participant count and defines successful engraftment using laboratory thresholds at a fixed post-transplant time. This is a binary endpoint: the outcome classification is whether the specified criteria were met. In general, binary outcomes can be reported as counts and proportions, with confidence intervals used to convey uncertainty around an estimated proportion. Those statistical summaries are not reported for the primary endpoint in the registry record, so no estimate or precision statement can be made from the endpoint definition alone.

What does non-randomized allocation mean?

In general, random assignment helps balance both measured and unmeasured characteristics between treatment groups, on average. This study is listed as non-randomized, with strata defined by donor matching. The participants in these strata are not assigned to otherwise comparable groups by chance. Donor match is itself a basis for the grouping, so outcome differences between strata cannot be treated as an unbiased estimate of a treatment effect. An adjusted analysis might attempt to address measured differences, but the registry record reports no such analysis. It also does not report enough detail to judge what adjustment would be suitable.

The parallel model indicates that groups are followed in parallel rather than participants crossing between treatments. That description does not by itself establish that the groups are comparable. Masking is listed as none. In general, masking can reduce the influence of knowledge of treatment assignment on outcome assessment or reporting, where relevant. For a threshold-based laboratory endpoint, the possibility and importance of such influence depend on measurement and assessment procedures, which are not described in the registry record.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. Its width reflects precision: wider intervals indicate greater uncertainty about the value being estimated. A p-value, when used, addresses compatibility between data and a specified null hypothesis under a statistical model; it does not measure clinical importance or prove that a hypothesis is true. Neither confidence intervals nor p-values for the primary outcome are reported in the registry record. Without an outcome estimate and its denominator, precision cannot be assessed.

For safety counts, the at-risk figures give context for the reported affected-participant counts in each stratum. In general, count summaries are easier to interpret when event definitions, observation periods, and denominators are consistent and explicit. Here, the registry lists counts and participants at risk, but does not report detailed event timing, duration of risk, recurrence, or how participants with multiple events were handled. The safety entries should therefore be read as descriptive summaries, not as rates adjusted for follow-up time or as inferential comparisons.

What does the planning illustration represent?

The registry's sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as targeting a stated fraction of an observed effect. In general, a planning calculation explores how many participants might be needed under specified assumptions about an effect, variability, significance level, and power. Such a calculation is prospective and assumption-dependent; it is not the trial's observed power and does not establish that a study detected an effect.

The assumptions also say that time-to-event planning tables use total events, while other planning outputs use participants per arm. However, the registry record does not report a primary observed effect or numerical planning results. It also does not describe the effect estimate used as the basis of the illustration, the event assumptions, or whether the illustration matches the non-randomized two-stratum design. Accordingly, no sample-size conclusion can be drawn from those assumptions alone. The equal-allocation assumption should not be mistaken for a description of the actual stratum sizes.

What analyses are absent?

The record lists no analyses. It does not report a statistical model, an unadjusted or adjusted primary-outcome comparison, methods for missing measurements, subgroup analyses, multiplicity control, or sensitivity analyses. It also does not report an analysis population, such as whether the primary outcome includes every enrolled participant or only those with observed measurements. These omissions limit interpretation because analysis choices can affect the estimate and its uncertainty. General statistical explanations describe what those methods would mean; they do not imply that any method was used in this study.

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("Stratum 1", "Stratum 2")
n      <- c(87, 5)
events <- c(87, 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  Stratum 1  87  87  100.0  95.8  100.0  95.8  100.0  95.9  100.0
ARM  Stratum 2  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 one primary outcome measure and no analyses. It does not report a statistical analysis plan specifying how primary and secondary outcomes would be tested, whether multiple hypotheses were planned, or how multiplicity would be handled. In general, testing multiple outcomes or subgroups can increase the chance of apparently notable findings arising by chance. Prespecified testing strategies can help control that issue. No such strategy is reported in the registry record, so the extent to which multiplicity was considered is not reported in the registry record.

Missing-data handling is also not described. The record does not state how participants without an ANC or platelet assessment by 100 days would be classified, whether measurements outside the stated time point were accepted, or how incomplete follow-up was addressed. It does not report the number of participants with observed primary-outcome data or the denominator used for an analysis. In general, missing outcome information can affect both an estimate and its precision, especially if missingness is related to participants' health or outcomes. The record does not provide information to assess that possibility.

The analysis population is not reported in the registry record. It is therefore unclear whether the intended primary analysis covered all enrolled participants, participants who received a transplant, or a different defined group. Although enrollment and safety denominators are listed, those figures do not establish the primary-outcome analysis population. The registry also does not describe exclusions, protocol deviations, or sensitivity analyses. These are reporting gaps; they do not show that the study necessarily had missing data or that a particular analysis was performed.

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

Serious events with the highest arm-level rate: non-relapsed mortality (33.3%).

The registry reports serious adverse-event summaries separately for the two strata. For Stratum 1, 6 participants are listed as affected among 87 at risk; for Stratum 2, 2 participants are listed as affected among 6 at risk. The other-adverse-event counts are 0 among 87 at risk in Stratum 1 and 0 among 6 at risk in Stratum 2. Deaths are listed as 0 in Stratum 1 and 2 in Stratum 2. These are separate registry entries, not a head-to-head safety comparison.

The registry does not report the event definitions, observation period, event severity criteria, individual event narratives, or whether a participant could contribute to more than one category. It also does not explain the relationship between the listed deaths and serious adverse events. The term “Non-relapsed mortality” appears among the top serious-event terms with 33.3%, but its denominator and time frame are not reported in the registry record. That percentage should not be generalized to the full study population or assigned to a specific stratum based on the information reported.

In general, safety counts describe reported events during the specified study context; they do not establish that an intervention caused an event. Here, the registry provides no event attribution or adjusted comparison. The small safety denominators, especially in Stratum 2, also mean that the entries alone do not provide a precise comparative estimate.

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

The record establishes that the study was designed to evaluate engraftment and selected safety and feasibility outcomes after CD3+ and CD19+ depletion of peripheral stem cell grafts. It specifies an engraftment definition based on ANC and platelet thresholds by 100 days post transplant. It also reports selected serious adverse-event, other adverse-event, and death counts by stratum. Those details allow readers to understand the endpoint and the scope of the recorded safety summaries.

The record does not report the primary engraftment result, so it cannot show how many participants met the stated definition. It also does not report a statistical estimate comparing the intervention with an alternative. Since the study is non-randomized and the strata differ in donor matching, differences between strata would not by themselves establish an intervention effect. No causal claim about treatment benefit or harm follows from the listed design and counts.

The safety information likewise has limits. Counts are not accompanied by event-level descriptions, consistent follow-up details, or an explanation of attribution. The listed “Non-relapsed mortality” percentage lacks a reported denominator and time frame. These omissions prevent a complete interpretation of the event summaries, and the counts should not be treated as a comprehensive safety assessment.

In general, a clinical result is more informative when the outcome estimate, analysis denominator, uncertainty interval, and analysis methods are all reported. Those elements are not reported for the primary endpoint. The registry entry is therefore informative about the study's question, design, endpoint definition, and some adverse-event reporting, but it is insufficient to quantify engraftment, estimate precision, or compare outcomes causally.

14. Why This Trial Matters Statistically

This study illustrates why a carefully defined endpoint and a clearly reported result are both necessary. The registry gives a specific binary definition of successful engraftment, including the ANC and platelet thresholds and the 100-day assessment point. That makes the intended outcome interpretable. But without the number meeting the definition, its denominator, and an uncertainty estimate, readers cannot judge the observed result or its precision.

The donor-match strata also demonstrate an important design issue. A non-randomized comparison between groups defined by different donor matching categories is not equivalent to a randomized comparison of treatments. Stratum membership may be related to the context in which transplantation occurs, and the registry does not report an analysis that adjusts for differences. Statistical language should preserve that distinction: descriptive group summaries are not automatically comparative treatment effects.

Safety summaries require similar care. Counts should be read with their at-risk denominators and with attention to whether definitions, follow-up, and event attribution are clear. The record includes those counts by stratum but does not report details needed for a fuller comparative assessment. The “Non-relapsed mortality” percentage is not interpretable as a population-level risk without its denominator and time frame.

Finally, planning assumptions are not findings. The registry describes a sample-size illustration, but reports no numerical planning results or observed primary effect. A planning calculation cannot substitute for reported outcome data, and it should not be described as observed power. Together, these features make the study a useful case for distinguishing the endpoint a trial intends to measure, the design used to collect evidence, and the results actually available for interpretation.

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 leaves the primary outcome without a reported result. It does not give the number meeting the engraftment definition, the denominator, missing-measurement details, or an uncertainty estimate. This prevents assessment of the observed endpoint and its precision. The record also does not specify the primary analysis population or the handling of participants who may not have had the required measurements by 100 days.

The non-randomized design limits comparisons between donor-match strata. Because the strata are defined by matching categories, they are not like-for-like controls. The record does not report adjusted estimates, baseline characteristics, or methods for addressing differences between groups. It also does not describe the allocation process beyond listing it as non-randomized.

Reporting detail is limited for treatment and safety. Part of the Stratum 1 description is truncated. The record does not report detailed graft-processing procedures, adherence, treatment deviations, or event attribution. Safety summaries lack event timing, definitions, and follow-up context; the denominator and time frame for the listed “Non-relapsed mortality” percentage are not reported. The registry does not report the extent of follow-up or whether all participants were observed for the same period.

Finally, the record lists no statistical analyses and does not provide the statistical plan, multiplicity approach, missing-data method, or sensitivity analyses. It gives assumptions for a planning illustration but no numerical planning outputs or observed effect underlying that illustration. These limitations concern what can be concluded from the registry record; they do not establish that unreported procedures or analyses were not conducted outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation for T and B Cell Depletion — NCT00579124.
• Registry record last updated 2025-02-03; status last verified 2025-01.
• Results first posted 2024-01-18.
• 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 describes a completed Phase 2, non-randomized, parallel study of CliniMACS CD3+ and CD19+ depletion for peripheral stem cell transplantation in patients with immunodeficiencies. Patients are organized into two donor-match strata, and the listed primary endpoint is successful engraftment by 100 days, defined by ANC >500 and platelet count >20 x 109/l.

Enrollment is listed as 93. The registry reports stratum-specific safety counts, but no primary-outcome results or statistical analyses. The study's non-randomized strata are not a like-for-like control comparison. The record therefore supports a description of the design, endpoint, and selected safety entries, but does not provide a quantitative estimate of engraftment or a causal comparison of treatment outcomes.