Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors (NCT01158118), a non-randomized phase 2 study. The primary outcome is Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation.

2. Clinical Question

3. Trial Design

The registry record describes a Phase II, non-randomized, unmasked, parallel study sponsored by Washington University School of Medicine. Enrollment was 48. The study began on 2011-04-01, had primary completion on 2014-01-15, and is listed as completed. These administrative details establish the study's recorded design and status; they do not establish that an efficacy result was reported.

The two listed arms had different roles. Arm 1 was the donor arm, in which sibling donors underwent mobilization and leukapheresis. Arm 2 was the recipient arm, which describes conditioning regimens and transplantation-related care. Because donors and recipients differ in population, treatment context, and outcomes, the arms are not a like-for-like comparison. The registry record explicitly indicates that the study was not randomized and that the arms are not a control comparison.

The donor regimen describes GM-CSF on Days 1-5, IV plerixafor on Day 5, and leukapheresis on Day 5. It notes a GM-CSF dose change after the first 4 donors. The recipient arm lists several conditioning approaches, including fludarabine and busulfan with or without thymoglobulin, as well as regimens involving total body irradiation, cyclophosphamide, or busulfan. These recipient details describe transplant care; they do not define a randomized comparison of mobilization strategies.

The primary endpoint concerns the count of donors requiring a second collection to reach a minimum CD34 cell yield. The record also lists secondary outcomes relating to donor toxicity and cell collection, along with recipient engraftment and graft-versus-host disease outcomes. There are no analyses listed in the registry record, and outcome estimates for the primary endpoint are not reported in the registry record. Randomization procedures, masking, and an allocation-based treatment contrast are not part of the design described.

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

Reasons for not completing this period:

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 Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation, measured over Up to 6 days.

The primary endpoint is the number of donors requiring a second collection to obtain a minimum CD34 cell yield of 2 x 10^6 per kilogram of recipient weight, the threshold described as necessary for allogeneic stem cell transplantation. Its time frame is up to 6 days. In practical terms, this endpoint counts donors whose first collection did not meet the stated minimum and who therefore needed another collection.

This endpoint is relevant to the study's mobilization question because it focuses on whether the collection process reaches a specified cell-yield target without a repeat procedure. The registry description frames the aim as reducing the number of donors requiring a second collection compared with historical controls mobilized with GM-CSF or plerixafor alone. It also states that a reduction in failed first leukapheresis from 40% to less than 10%, as seen with G-CSF alone, would be considered clinically meaningful. That benchmark is part of the stated rationale; it is not a reported result from this trial.

The outcome is a count of participants, not a continuous measure of cell yield or a time-to-event measure. To interpret it as an effect of the combination, the observed count would need to be reported along with an appropriate comparison and uncertainty. Neither a primary-endpoint result nor a comparison estimate is reported in the registry record. The endpoint definition alone therefore explains what the study intended to measure, but not whether the intended reduction was observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary endpoint is a count of donors who require a second collection to reach the stated CD34 threshold. A count describes how many participants experienced a defined event. Counts are most interpretable when accompanied by the number of participants at risk, a clear observation period, and a defined analysis population. The registry gives the endpoint time frame as up to 6 days, but the primary outcome count and its denominator are not reported in the registry record.

How would an effect be estimated? A treatment effect would require a comparison of the repeat-collection outcome under the mobilization approach with an appropriate alternative. The endpoint description refers to historical controls receiving GM-CSF or plerixafor alone. Historical comparisons can be affected by differences in participant selection, clinical practice, measurement, and follow-up between the current study and earlier experience. As a general statistical principle, random allocation helps balance both known and unknown prognostic factors between concurrent groups. This study is listed as non-randomized, and its donor and recipient arms are not a valid direct comparator for the primary donor endpoint. The registry record does not report a comparative effect estimate against the historical controls.

What does uncertainty mean? A confidence interval is a range of estimates compatible with the observed data under a specified statistical model and its assumptions. It conveys precision as well as direction and magnitude. A small study may yield an estimate with substantial uncertainty, even when the point estimate appears favorable or unfavorable. No confidence interval or other uncertainty measure for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

Why distinguish counts from rates? A count is the number of participants with an event. A rate or proportion relates that count to a specified denominator. The primary endpoint is described as a count, and a comparison of counts alone may be misleading if the contributing group sizes differ. For a transparent interpretation, the event count and the eligible donor denominator would need to be reported together, with clear rules for who was included and how a second collection was classified. The registry record does not report those primary-endpoint details.

What is the role of the stated benchmark? The endpoint description says a reduction in failed first leukapheresis from 40% to less than 10%, as seen with G-CSF alone, would be clinically meaningful. This is a stated benchmark, not the observed result of the study. A benchmark can help explain why investigators selected an outcome, but it does not establish the observed effect, the source or comparability of the historical data, or the uncertainty around a trial estimate. The record does not report a sample-size justification or the assumptions used to set enrollment.

How should the planning illustrations be read? The planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. The instructions for the planning display distinguish participant counts per arm from total event counts for time-to-event outcomes. These are planning illustrations, not observed power. No calculated planning values or observed primary effect are reported in the registry record, so the illustrations cannot establish the power achieved by this trial or validate its enrollment target. The registry record also does not report a sample-size justification tied to the primary endpoint.

What can be inferred from the analysis listing? The registry record lists zero analyses. A listed analysis would ordinarily identify an outcome, a comparison, and a statistical result; without such a result, there is no basis to assess a p-value, adjusted estimate, or model assumptions for the primary endpoint. General statistical principles cannot replace the missing trial-specific analysis. The registry record does not report whether an analysis plan specified covariate adjustment, handling of historical controls, or sensitivity analyses.

Why is the study structure important? The arms are parallel in their organization, but parallel structure alone does not make them comparable. Donors and recipients have different roles and outcome measures. The donor arm addresses mobilization and collection; the recipient arm includes transplant-related outcomes such as engraftment and graft-versus-host disease. Combining or contrasting those groups as though they were randomized treatment groups would not answer the primary question. The non-randomized design and the absence of a reported primary analysis limit what can be concluded statistically from the registry record.

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("Arm 1 - Donor")
n      <- c(23)
events <- c(4)
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  Arm 1 - Donor  23  4  17.4  5.0  38.8  7.0  37.1  7.1  37.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes, including donor infusion toxicity and cell-collection targets, as well as recipient engraftment and acute and chronic graft-versus-host disease outcomes. It records 12 outcome measures and zero analyses. The outcome list does not establish which outcomes were analyzed, which were designated as key secondary outcomes, or whether any result was statistically tested.

When a study evaluates many outcomes, the chance of at least one apparently unusual result can increase if each is tested separately. As a general statistical principle, a prespecified testing hierarchy or a multiplicity adjustment can help control that issue. The registry record does not report a multiplicity strategy, a hierarchy of hypotheses, or adjusted results. It is not possible to determine how multiple outcomes were handled.

The record also does not report missing-data counts, reasons for missing measurements, or methods used to handle missing outcomes. For the primary endpoint, the number of eligible donors contributing data and the handling of incomplete collection information are not reported in the registry record. No assumptions about missingness or imputation should be attributed to the study.

Analysis populations are not described in the information recorded. The registry record does not state whether outcomes were analyzed for all enrolled participants, only participants who received the intended mobilization, or another defined population. Nor does it report exclusions or deviations from the planned treatment approach. These omissions restrict assessment of how representative any outcome would be of the enrolled group, even if an estimate were available.

12. Safety Results

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

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: sepsis (9.5%), cardiac arrest (4.8%), diarrhea (4.8%), enterocolitis infectious (4.8%), fatigue (4.8%).

The registry safety entries distinguish serious adverse events from other adverse events and give separate at-risk and affected counts for the donor and recipient arms. In the donor arm, the serious-event fields list 1 affected participant among 23 at risk; the other-event fields list 23 affected among 23 at risk. In the recipient arm, the serious-event fields list 8 affected among 21 at risk; the other-event fields list 21 affected among 21 at risk. These are registry counts within separate populations, not a randomized safety comparison.

The listed serious-event terms and percentages are sepsis, 9.5%; cardiac arrest, 4.8%; diarrhea, 4.8%; enterocolitis infectious, 4.8%; fatigue, 4.8%; and lung infection, 4.8%. The registry record does not provide enough information alongside these terms to establish a causal relationship to a particular intervention. The terms should be understood as reported safety events, not proof that a study drug caused them.

The death fields are not reported in the registry record. The donor and recipient groups differ in clinical role and risk context, so their counts should not be compared as though treatment assignment were randomized. The safety entries also do not answer the primary question about the need for a second collection.

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

The registry record describes a Phase II study of plerixafor and sargramostim for mobilizing peripheral blood stem cells from normal, HLA-matched allogeneic sibling donors. It identifies a clinically relevant operational endpoint: whether donors need a second collection to reach the minimum CD34 cell yield specified for transplantation. It also records donor and recipient safety and transplant-related outcomes as areas of interest.

What the record does not establish is whether the combination reduced the number of donors needing another collection. The primary endpoint result, a comparison estimate, and uncertainty measures are not reported in the registry record. The historical-control rationale and its stated clinically meaningful benchmark describe the question investigators intended to address; they are not evidence that the target was achieved.

The non-randomized design matters to interpretation. The donor and recipient arms are different populations with different outcomes, rather than intervention and control groups. The description of historical controls does not include their outcome data or a reported comparative analysis. As a result, the registry information does not support a direct causal conclusion about the effect of the combination relative to either single agent.

Safety figures describe affected participants in the separate donor and recipient groups, while the listed serious-event terms provide additional context. They do not, by themselves, identify whether events were caused by treatment, and they cannot be used as a substitute for a comparative safety analysis. The registry record does not report death counts.

In general, a clinical trial result is most informative when the outcome definition, analysis population, event counts, comparison, and uncertainty are available together. Here, the design and endpoint are described, but the primary analysis is not reported. The appropriate conclusion is therefore about the scope and limits of the registry information, not about whether the mobilization strategy was successful or unsuccessful.

14. Why This Trial Matters Statistically

This study poses a practical statistical question about a measurable step in stem-cell collection: how many donors need a second collection to reach a stated minimum CD34 yield. The endpoint links mobilization to an operational outcome that matters to the collection process, rather than relying only on a laboratory measurement. Specifying a threshold and a time frame helps define what counts as an endpoint event.

The record also illustrates why a well-defined endpoint does not guarantee an interpretable effect estimate. For an outcome count to support a treatment comparison, readers need the observed count and denominator for the relevant population, along with a suitable comparator and uncertainty. The registry record does not report the primary count or an estimated contrast. The stated historical benchmark provides context for the research question but cannot replace those data.

The distinction between donors and recipients is statistically important. They have different roles, exposures, and outcome measures, and their arms cannot be treated as exchangeable groups. This is especially relevant when a study record lists parallel arms: the label describes the arrangement, but does not establish a causal comparison. The non-randomized design and the reliance on historical controls make comparability a central interpretive concern.

The study is also a useful example of how registry entries can document design and safety information without presenting a complete analysis. The record lists outcomes and adverse-event counts, but no analyses. Readers should distinguish outcome definitions and planning rationale from observed efficacy results. That distinction prevents an intended comparison or a clinically meaningful benchmark from being mistaken for evidence of the study's result.

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 main limitation for statistical interpretation is that the registry record does not report the primary endpoint result, its denominator, or an estimate comparing the study outcome with historical controls. Without these, neither the magnitude nor precision of the endpoint can be assessed. The record also lists zero analyses, so there is no reported primary analysis to evaluate.

The study is non-randomized, and its donor and recipient arms are not a like-for-like comparison. The primary endpoint description invokes historical controls, but the record does not provide their data or an analysis addressing differences between historical and current participants. Consequently, the comparative rationale cannot be verified from the recorded information.

The donor regimen changed after the first 4 donors, with GM-CSF dosing described as 10 mcg/kg for those donors and 5 mcg/kg for the remaining donors. The registry record does not report subgroup results by dose or explain whether the change was incorporated into the analysis. This limits interpretation of the regimen as a single uniform exposure.

The record does not report a sample-size justification, analysis populations, missing-data methods, or a multiplicity strategy. It also does not report primary outcome estimates for the listed secondary outcomes. Safety information is presented separately for donor and recipient groups, which should not be compared causally. The death fields are not reported in the registry record. These limitations concern what can be concluded from the registry information; they do not establish that analyses or additional information are unavailable elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors — NCT01158118.
• Registry record last updated 2017-06-05; status last verified 2017-05.
• Results first posted 2017-05-03.
• 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

NCT01158118 is a completed Phase II, non-randomized, unmasked, parallel study sponsored by Washington University School of Medicine. The registry record reports enrollment of 48, a start date of 2011-04-01, and primary completion on 2014-01-15. It evaluated plerixafor with sargramostim for mobilization of peripheral blood stem cells from sibling donors.

The primary endpoint was the number of donors requiring a second collection to obtain a minimum CD34 yield of 2 x 10^6 per kilogram of recipient weight, with a time frame of up to 6 days. The registry record lists donor and recipient arms, but they are not a like-for-like comparison. It lists 12 outcome measures and zero analyses.

The primary endpoint result and a comparative effect estimate are not reported in the registry record. Safety entries include separate donor and recipient counts and listed serious-event terms. The record does not report death counts, a multiplicity strategy, missing-data methods, or analysis populations.