Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies (NCT00914849), a non-randomized phase 2 study. The primary outcome is Number of Donors Treated With IV AMD3100 Who Required a Second Collection to Obtain the Minimum CD34/kg (2 X 106) Necessary for Allogeneic Stem Cell Transplant.

2. Clinical Question

This question is operational: it focuses on whether the planned collection reached the target, rather than on a direct comparison of clinical outcomes between randomized treatment groups. The study also lists recipient outcomes, including neutrophil engraftment and acute graft-versus-host disease, as well as donor infusional toxicity and pharmacokinetic measures. Those outcomes broaden the descriptive scope, but they do not turn the donor and recipient arms into comparable treatment groups. The record does not report a randomized estimate of AMD3100’s effect against a control intervention.

3. Trial Design

This was a Phase II, non-randomized, parallel study sponsored by Washington University School of Medicine. The registry records enrollment of 68 and a masking designation of none. The study began in 2009-08, had primary completion in 2011-01, and is listed as completed. The record does not report a sample-size justification or a protocol rationale for the enrollment target.

The two arms have different functions. Arm 1 is the donor arm: donors received intravenous AMD3100 and leukopheresis, with the Day 2 dose and collection specified if the cells collected on Day 1 were insufficient. Arm 2 is the recipient arm. Its description refers to standard care and physician choice of myeloablative or non-myeloablative chemotherapy, with or without total body irradiation. The recipient treatment description is not a matched control condition for the donor intervention.

Because allocation was non-randomized and the arms consist of donors and recipients, comparisons between their outcome counts would not isolate a treatment effect. The populations differ by role, and the record does not describe an allocation process that makes them exchangeable. The appropriate reading is therefore to treat each arm’s outcomes as descriptive information about its own participants, not as a head-to-head estimate.

The registry lists 14 outcome measures. The primary outcome concerns the need for a second collection, while the secondary outcomes include donor infusional toxicity, recipient neutrophil engraftment, pharmacokinetic measures, acute graft-versus-host disease, and time to neutrophil engraftment. No analysis results are listed in the registry record. The record also does not report the statistical analysis plan, any interim analyses, or a detailed account of how outcomes were summarized.

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:

Analysis population for the primary outcome, as defined in the registry: 3 donors failed to reach target after two collections and 1 donor withdrew consent after failing to reach the goal on the first collection.

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: One recipient was not transplanted because of donor withdrawal of consent to collect a second day after a failed first day apheresis attempt.

6. Primary Endpoint

The registry lists the primary outcome as Number of Donors Treated With IV AMD3100 Who Required a Second Collection to Obtain the Minimum CD34/kg (2 X 106) Necessary for Allogeneic Stem Cell Transplant, measured over Completion of enrollment of all donors (17 months).

The primary endpoint is the number of donors treated with intravenous AMD3100 who required a second collection to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell transplant. The stated timeframe is completion of enrollment of all donors (17 months). The endpoint is a count of participants meeting a defined collection-related condition, rather than a continuous measurement of cell yield or a time-to-event outcome.

Such an endpoint can be useful because it expresses collection sufficiency in a way linked to the practical goal stated in the registry: reducing the number of donors who need another collection. It is distinct from asking how much cell yield varied among donors or whether recipients later engrafted. A count of donors requiring a second collection can summarize the frequency of that operational event, but by itself it does not describe the amount by which any collection fell short, the timing or burden of additional collection, or recipient outcomes.

The record’s endpoint description also notes that 3 donors failed to reach the target after two collections and 1 donor withdrew consent after failing to reach the goal on the first collection. These statements provide context about target failure and withdrawal; they do not give a separate exact count of donors who required a second collection. The registry record does not report an endpoint estimate with a defined analysis population, nor does it state how the withdrawal was handled in an endpoint analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the type of outcome and the way participants were organized. The primary endpoint is a count of donors meeting a binary condition: whether a donor required a second collection to obtain the stated minimum cell target. For an outcome of this kind, a result may be reported as the number of participants with the event, often alongside the number evaluated. That description is general; the registry record does not provide a primary endpoint result in that form.

What does a participant count convey?

A count answers how many people in an analysis group had an event. It does not, on its own, show the distribution of measurements among those people or explain why the event occurred. For the collection endpoint, the event is defined by the need for another collection in relation to the target. A count could be interpreted only with a clear denominator and a stated analysis population. The registry gives a narrative about target failures and withdrawal, but it does not report the exact endpoint count and its denominator as an analyzed result.

When the event is binary, statistical uncertainty is commonly expressed with an interval around an estimated event frequency. General interpretation of such an interval depends on how the interval was constructed and on the number of observed events and participants. No endpoint estimate or confidence interval is reported in the registry record, so its precision cannot be described. It would not be appropriate to reconstruct an interval from the narrative because the endpoint count and analysis rules are not fully stated.

Why does the design matter?

Random assignment is one way to make treatment groups comparable on average, but this study is listed as non-randomized. More importantly, the arms are donors and recipients, which are distinct clinical roles. The donor arm received AMD3100 and leukopheresis; the recipient arm received physician-choice transplant conditioning. Consequently, a numerical contrast between the arms would not be a valid like-for-like treatment comparison. The registry explicitly flags that the arms are not a control comparison. The record does not report an alternative comparative design or adjustment strategy that would support a causal contrast.

A parallel structure means that the registry describes separate arms, but the label does not by itself imply random allocation or comparability. Masking is listed as none. No further information about outcome assessor masking or procedures to reduce measurement bias is reported in the registry record. General methods considerations such as confounding, selection, and outcome ascertainment therefore remain relevant, but the record does not give enough detail to assess their magnitude.

How should the planning illustrations be read?

The record describes sample-size illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between arms, and a normal approximation. The intended effect is defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations refer to a total number of events using the Schoenfeld method; other illustrations refer to participants per arm. These are planning assumptions, not evidence that the trial was designed with those assumptions, and the record explicitly distinguishes the illustrations from the trial’s own design.

In general, a sample-size calculation asks how much information a future study might need to detect a chosen effect under stated assumptions. It is not a measure of the probability that the observed finding is true, and it is not observed power. A planning illustration based on an observed effect can vary substantially when the underlying estimate is uncertain. The registry record does not report a sample-size justification for this study, and no actual illustration values are stated in the information available for interpretation. Such planning material cannot replace a reported trial estimate and its uncertainty.

What can pharmacokinetic and time-to-event methods add?

The secondary outcomes include mean maximum plasma concentration, half life, and mean area under the curve for intravenous AMD3100, as well as time to neutrophil engraftment. Pharmacokinetic measures describe drug concentration over time and can help characterize exposure. Time-to-event methods account for both when an event occurs and whether observation ends before that event is recorded. These are general descriptions of the methods’ purposes; the registry record does not give the underlying measurements, event times, censoring details, or fitted analyses.

The record does not specify a statistical plan for these outcomes. For example, it does not report the summary method for pharmacokinetic measures, the definition of time origin for engraftment, or the handling of participants without a recorded event. These details matter because alternative definitions and analysis choices can change the interpretation. No methods should be attributed to the study beyond those explicitly stated in the registry record.

Why can over-dispersion matter?

General count-data methods sometimes account for over-dispersion: variation greater than expected under a simple count model. That issue can affect standard errors and confidence intervals when counts vary more widely than the model assumes. The primary endpoint is a participant count, but the registry record does not report an over-dispersion assessment or a count-model analysis. It would be speculative to claim that such a method was used or needed for the posted primary result.

Overall, the methodological record supports explaining the endpoint’s form and the design constraints, but it does not support reproducing an inferential analysis. The primary estimate, confidence interval, statistical model, covariate adjustment, and outcome-specific analysis populations are not reported in 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(29)
events <- c(10)
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  29  10  34.5  17.9  54.3  19.9  52.7  19.9  52.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary collection endpoint and secondary measures of donor toxicity, recipient engraftment, pharmacokinetics, acute graft-versus-host disease, and time to neutrophil engraftment. When a study assesses multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each outcome is tested separately. General approaches to multiplicity include prespecifying a hierarchy, adjusting significance thresholds, or clearly treating secondary results as exploratory. The registry record does not report whether any such approach was planned or used.

The record lists 0 analyses. It therefore does not provide a collection of outcome-specific estimates or tests from which to assess selective emphasis, multiplicity adjustment, or consistency across outcomes. The registry record also does not report an analysis plan, a prespecified hierarchy beyond identifying a primary outcome, or whether the secondary outcomes were confirmatory or exploratory.

Missing-data handling is not reported in the registry record. The primary outcome narrative notes that 1 donor withdrew consent after failing to reach the goal on the first collection, but it does not state how that person was included in an endpoint denominator or analysis. It also does not describe missing outcome observations, follow-up completeness, censoring, imputation, or sensitivity analyses. The withdrawal should be noted as part of the record, without assuming how it was treated statistically.

Analysis populations are not reported in the registry record. The adverse-event summary gives 33 participants at risk in each arm for its serious and other event counts, while the total enrollment is recorded as 68. The record does not explain the relationship between these figures or identify whether other outcome analyses used the same populations. No total or reconciled analysis denominator should be inferred from the available information.

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 non-serious adverse event terms

The serious adverse-event summary lists 33 donors at risk, with 0 affected, and 33 recipients at risk, also with 0 affected. For other adverse events, the summary lists 33 donors at risk and 33 affected, and 33 recipients at risk and 33 affected. These figures describe the registry’s event categories and the counts attached to them; they do not establish the causes, timing, duration, or clinical consequences of the events.

Zero recorded serious events in a group is not proof that serious events cannot occur. General interpretation of an observed event count depends on the number of participants observed, the length and completeness of follow-up, and how events were defined and collected. Those details are not reported in the registry record. The listed counts should therefore be read as registry summaries, not as a complete estimate of risk over a specified exposure period.

The record does not list serious adverse-event terms, and deaths are not reported in the registry record. It also does not provide event-level descriptions or attribution to AMD3100, leukopheresis, transplant conditioning, or other aspects of care. The other-event counts should not be described as serious events: the registry separates them from the serious category. Without further detail, these summaries do not support comparisons of safety between the donor and recipient arms, which are not like-for-like groups.

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

The study record identifies a practical transplant-related question: whether donors treated with intravenous AMD3100 needed a second collection to obtain the stated minimum CD34/kg (2 X 106) for allogeneic stem cell transplant. It also describes the Day 1 mobilization and collection procedure and the conditional Day 2 procedure. The primary endpoint is therefore tied to collection sufficiency, not to a direct measure of recipient benefit.

The narrative reports 3 donors who failed to reach the target after two collections and 1 donor who withdrew consent after failing to reach the goal on the first collection. These details are relevant to understanding the study record, but they do not supply a complete analyzed endpoint result. The exact number of donors requiring a second collection is not separately reported as an outcome estimate. No estimate of uncertainty is reported either.

The record also lists recipient and donor outcomes beyond the primary endpoint. It includes counts for serious and other adverse events and names secondary measures, but numerical results for the listed secondary outcomes are not reported in the registry record. The adverse-event counts do not establish causation, and the arms cannot be treated as comparative treatment groups because they are non-randomized groups with different roles.

Accordingly, the posted information does not establish how large or precise any effect was, nor does it support a claim that the study did or did not achieve its stated aim. It describes the intended question, study structure, some outcome definitions, and selected registry counts. A fuller interpretation would require the primary outcome estimate, its denominator and uncertainty, details of outcome handling, and results for the listed secondary measures. The study record alone does not provide those elements.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an outcome definition and an outcome result. The record defines a concrete collection-related endpoint and states why it matters to the study’s aim: reducing the number of donors who require a second collection. Yet the registry information does not separately report the analyzed count for that endpoint. A clearly framed question is not a substitute for a result estimate.

The design also highlights why the role of each arm must be understood before comparing numbers. Donors received the mobilization procedure, while recipients underwent transplant care. Even though the record uses a parallel-arm structure, the groups do not form a randomized treatment-versus-control comparison. Statistical contrast cannot overcome this structural difference by itself.

The registry’s adverse-event summaries show how counts can be reported without enough context for a full safety interpretation. Counts need a clear observation period, event definitions, and an understanding of who was included. A zero count is a description of recorded events, not evidence that the underlying risk is absent. Similarly, counts of other events cannot be interpreted as evidence of severity or causation without event details.

The listed range of secondary outcomes also makes multiplicity and outcome reporting relevant. The registry names pharmacokinetic, toxicity, engraftment, and graft-versus-host disease outcomes, but does not report their numerical analyses. Without estimates, uncertainty, and a stated analysis plan, readers cannot assess how results compare across outcomes or whether conclusions were prespecified. The record thus demonstrates the value of reporting both methods and results transparently, especially when a study has multiple outcomes and a non-comparative design.

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 interpretation is that the registry record does not report a separate numerical estimate for the primary endpoint, nor an interval describing its precision. The narrative mentions donors who did not reach the target and a withdrawal, but does not state the analyzed count of donors requiring a second collection or define the corresponding analysis denominator. The endpoint result therefore cannot be reconstructed reliably from the narrative.

The study is non-randomized, and its donor and recipient arms are not comparable control groups. The record does not describe a separate donor control arm, a random allocation procedure, or an adjustment strategy that could support a causal comparison. Conclusions about treatment effects cannot be drawn by contrasting outcomes across these different populations.

Other relevant details are not reported in the registry record: eligibility criteria, baseline characteristics, outcome ascertainment procedures, follow-up completeness, handling of missing data, and analysis populations. The record also does not provide the statistical analysis plan, any interim analyses, or the rationale for the enrollment target. These gaps limit assessment of selection, measurement, and analytic choices.

The registry includes 14 outcome measures but lists 0 analyses. Numerical results for the secondary outcomes are not reported in the record. Safety information is limited to event counts and does not include serious-event terms, event timing, duration, attribution, or deaths. These constraints mean that neither the primary endpoint’s precision nor the broader clinical outcome profile can be evaluated from the registry record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies — NCT00914849.
• Registry record last updated 2017-05-17; status last verified 2017-04.
• Results first posted 2016-08-24.
• 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

NCT00914849 is a completed Phase II, non-randomized, parallel study sponsored by Washington University School of Medicine. The record lists enrollment of 68, no masking, study start in 2009-08, and primary completion in 2011-01. Donors received intravenous AMD3100 with leukopheresis, with another collection specified if the initial collection was insufficient; recipients received physician-choice transplant conditioning.

The primary endpoint concerns the number of donors requiring a second collection to reach the stated CD34/kg target. The record gives narrative information about target failures and a withdrawal, but does not separately report the analyzed endpoint count or its precision. It lists 14 outcome measures and 0 analyses. Adverse-event summaries report 0 serious events in each arm and other events in all participants listed as at risk; deaths are not reported in the registry record. The arms are not a like-for-like control comparison.