Maraviroc in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maraviroc in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation (NCT00948753), a non-randomized phase 1, phase 2 study. The primary outcome is Safety of Maraviroc.

2. Clinical Question

3. Trial Design

This completed study combined Phase 1 and Phase 2 components and used a non-randomized, unmasked, parallel-group design. Enrollment was 38. The registry record lists a Phase 1 cohort assigned to maraviroc 150mg twice daily, a Phase 1 cohort assigned to 300mg twice daily, and a Phase 2 cohort assigned to 300mg twice daily. These are dose and phase cohorts, not randomized alternatives to a control treatment. Differences between their results cannot be interpreted as if participants had been randomly assigned to otherwise comparable groups.

Maraviroc was added to standard GVHD prophylaxis. The study description says it began after the last dose of the chemotherapy conditioning regimen and continued until day 30 after stem-cell infusion. The primary safety outcome has a registry timeframe of 1 year. These details describe the planned treatment and outcome timeframe; they do not establish the amount of exposure or follow-up completed by every participant.

The registry lists a start date of 2009-06, primary completion of 2011-04, and status of COMPLETED. Abramson Cancer Center at Penn Medicine is listed as sponsor. The study description emphasizes both safety and prevention of GVHD, while the registered primary outcome is safety. Secondary outcomes include pharmacokinetic profile, chronic GVHD, early mortality after transplant, and relapse during the study period. The registry record does not report a randomized comparator, masking, or a formal statistical analysis plan.

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.

Phase 1

Phase 2

Analysis population for the primary outcome, as defined in the registry: patients receiving SCT

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: Participants totaled 13 for phase I and 25 for phase 2.

6. Primary Endpoint

The registry lists the primary outcome as Safety of Maraviroc, measured over 1 year.

The primary outcome is titled Safety of Maraviroc and is defined as the number of adverse events following exposure to maraviroc among patients receiving SCT. Its registry timeframe is 1 year. An adverse-event count is intended to describe the burden of events recorded during the specified period. Unlike a simple yes-or-no outcome, a count can distinguish between participants with different numbers of events, if those event totals are reported and their observation periods are sufficiently clear.

Counts can be useful in safety studies because they retain information about repeated events rather than reducing the outcome to whether a participant experienced any event. However, the count of events is not the same as the number of participants affected: one participant may contribute more than one event. The posted safety results report numbers of participants affected by serious and other adverse events in each cohort. They do not report the total number of adverse events for the primary outcome, so the endpoint as defined cannot be fully characterized from those figures alone.

Safety monitoring is relevant when a drug is given alongside standard prophylaxis during transplantation. The results describe what was recorded in this study; without a randomized control group and a complete account of event counts and observation, they do not establish a causal difference in safety.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what can and cannot be concluded from these registry results. The distinctions below are general statistical explanations; they do not imply that a particular model or analysis was used in this study.

What does a count endpoint measure?

A count endpoint records how many events occur, rather than only whether at least one event occurred. It can preserve information about repeated events, but interpreting it requires the event totals and a clear account of the time participants were observed. A count of participants affected is a different summary: it records how many people had an event in a category, without showing whether each person experienced one event or several. The primary outcome is defined as the number of adverse events, whereas the posted safety figures give participants affected by serious and other adverse events. Those summaries should not be treated as interchangeable.

For count data, a Poisson model is a common starting point. Its usual assumption is that the event-count variance matches the mean. In practice, counts can be more variable than that assumption allows, a condition called over-dispersion. When over-dispersion is present, a model that assumes less variability may produce standard errors that are too small and intervals that are too narrow. Other approaches, such as a negative binomial model, can allow additional variability. These are general options, not methods reported for this trial; no statistical analysis is listed in the registry record.

Exposure time also matters for event counts. Participants observed for longer may have more opportunity to experience or report events. A rate analysis can account for different observation times when suitable person-time information is available. Person-time, the event totals needed for such a calculation, and details of observation by participant are not reported in the registry record. The posted affected-participant figures therefore do not support a rate interpretation.

Why does allocation matter?

Randomization aims to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics at the start of a study. This study was non-randomized, so assignment to the listed phase and dose cohorts may be related to participant characteristics or clinical decisions. A difference in outcomes across cohorts could reflect those differences as well as dose, timing, or other factors. Statistical adjustment can sometimes address measured differences, but no adjusted analysis is reported, and adjustment cannot reliably remove bias from factors that were not measured.

The parallel-group structure means that the cohorts are distinct groups rather than repeated measurements on the same participants. That structure does not by itself make the groups comparable. The lack of masking can also matter for outcomes involving observation or reporting: knowledge of treatment may influence how events are assessed or recorded. The registry record does not describe blinded outcome assessment or procedures to limit such influence.

What would uncertainty estimates add?

A confidence interval is a general way to communicate the precision of an estimate. It gives a range of values compatible with the observed data under the assumptions of the chosen analysis. A narrow interval generally indicates greater precision than a wide one, while neither interval width nor a statistical test establishes clinical importance. The posted results contain no reported interval estimates or inferential analyses. Consequently, readers cannot use the registry record to assess statistical precision for the affected-participant counts or a formal difference between cohorts.

For a count outcome, an analysis might estimate a mean count or an event rate and attach an interval, with model assumptions suited to the data. A comparison might also adjust for relevant participant characteristics if those data and a prespecified approach were available. None of those estimates or model details is listed. The primary safety outcome is specified as an event count, but the posted figures are participant counts affected by event categories, leaving a gap between the defined endpoint and the displayed summaries.

How should planning illustrations be read?

Sample-size planning calculations are not descriptions of what happened in the trial. The planning illustrations associated with this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the figures are expressed as participants per arm; time-to-event calculations use a total event count. These are planning assumptions, not evidence that the study was designed or powered according to them. Sample-size justification for the trial is not reported in the registry record, and planning illustrations must not be read as observed power or as confirmation that an effect was detected.

In general, a sample-size calculation depends on the outcome, the effect considered important to detect, the variability of the data, the desired precision or power, and the analysis plan. If an effect observed in a study is used as the planning target, that value may be unstable, especially when estimates are imprecise. A planning exercise can show how assumptions influence a future design, but it cannot substitute for a prespecified design justification or for an uncertainty analysis of the results already observed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and no analyses. The primary outcome concerns safety; listed secondary outcomes include the pharmacokinetic profile of maraviroc, chronic GVHD, early mortality after transplant, and relapse during the study period. The record does not provide results or inferential analyses for these secondary outcomes. It also does not report how outcomes were prioritized beyond identifying the primary safety outcome.

Multiplicity arises when multiple outcomes, comparisons, time points, or subgroups are tested. Conducting many tests can increase the chance of a false-positive finding if each is interpreted in isolation. Statistical plans may address this by specifying a primary comparison, adjusting significance thresholds, or treating secondary analyses as exploratory. Such procedures are not reported in the registry record. Since no analyses are listed, there are no reported test results to interpret in light of multiplicity.

Missing-data handling is also not reported in the registry record. The posted cohort counts include participants listed as at risk for serious and other adverse events, but those figures do not explain whether all enrolled participants contributed complete follow-up for the 1-year primary timeframe, how incomplete follow-up was treated, or whether any events were missing. The record does not state whether analyses used an intention-to-treat, per-protocol, or other analysis population. It identifies the primary population as patients receiving SCT, but does not define a detailed analysis set.

These omissions limit interpretation of both the outcome summaries and their completeness. They do not establish that data were missing or that any particular analysis population was used; they mean that the registry record does not describe those procedures.

11. 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 entries list zero participants affected in each cohort: 0 of 7 in Phase 1: 150mg Maraviroc, 0 of 6 in Phase 1: 300mg Maraviroc, and 0 of 25 in Phase 2: 300mg Maraviroc. For other adverse events, the listed figures are 7 of 7, 6 of 6, and 17 of 25, respectively. These are counts of participants affected, not total counts of events. A participant may experience more than one event, and the posted figures do not describe event frequency per participant.

The serious-event result is a descriptive observation in these cohorts, not proof that serious events are impossible or that risk is absent. The record does not report confidence intervals, follow-up completeness, detailed event terms, or an inferential comparison across dose cohorts. The registry’s serious-event terms list is empty, so specific serious-event types are not identified there. Death counts are not reported in the registry record. The safety endpoint is described as a number of adverse events over a 1-year timeframe, but the posted affected-participant counts do not provide total event counts for that endpoint.

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

The posted results document adverse-event summaries for three maraviroc cohorts in patients undergoing non-myeloablative allogeneic SCT. The serious-event entries list no participants affected, while other adverse events are reported among participants in each cohort. Those observations describe what the registry record reports; they do not establish that maraviroc caused or prevented any event. Because standard GVHD prophylaxis was also given and there was no randomized control group, the separate contribution of maraviroc cannot be isolated from these results.

The cohort structure also limits dose interpretation. The Phase 1 cohorts received different doses, and the Phase 2 cohort received 300mg twice daily, but assignment was non-randomized. Differences in counts between cohorts could reflect differences in the participants, their clinical circumstances, or their observation, rather than a dose effect. No inferential analyses or uncertainty estimates are listed, so the precision of the observed summaries and the strength of any between-cohort contrast cannot be assessed from the record.

The stated primary endpoint is the number of adverse events during a 1-year timeframe. The posted safety figures give the numbers of participants affected by serious and other adverse events, not total event counts. They therefore do not fully represent the primary endpoint as defined. Nor do they provide enough information to compare event rates, since participant-level observation time and event totals are not reported in the registry record.

The registry describes prevention of GVHD as a study aim and lists GVHD-related and other secondary outcomes. The available safety counts do not establish whether GVHD was prevented, whether outcomes differed from standard prophylaxis alone, or how benefits and harms compare. The record also does not report the outcome analyses needed for those conclusions. The findings should be understood as descriptive safety information from a small, non-randomized study, rather than as a causal estimate or a complete evaluation of effectiveness.

13. Why This Trial Matters Statistically

This study illustrates a recurring statistical challenge in early clinical research: safety outcomes can be clinically important while the available data remain difficult to compare. The registry defines its primary outcome as an adverse-event count, but posts the number of participants affected in serious and other categories. Recognizing the distinction between events and affected participants is essential. Participant counts can describe how widely an event category occurred, while event totals are needed to characterize repeated events and support some count-based analyses.

The non-randomized, unmasked design also makes interpretation of dose cohorts more cautious. Such cohorts can provide descriptive information during study development, but a difference between them does not automatically represent a dose effect. This is especially important when the registry does not list adjusted estimates, uncertainty intervals, or inferential analyses. Statistical reporting is not merely about displaying counts; it also needs to make clear how groups were formed, what was measured, and how incomplete observation was handled.

The record further shows why endpoint definition and result format should align. A reader needs to know whether a summary represents events, people affected, or event rates, and how long participants were observed. Without total event counts and follow-up detail, the registered one-year safety endpoint cannot be reconstructed from the posted figures. This limits the ability to evaluate precision and compare results across cohorts or studies.

Finally, the existence of planning calculations does not show that a trial had adequate power, nor that it detected an effect. Planning assumptions and actual analyses answer different questions. Clear reporting of the rationale for enrollment, analysis populations, missing-data procedures, and multiplicity would help readers understand the evidential scope of a study. Those details are not reported in the registry record, making cautious descriptive interpretation the statistically appropriate reading.

14. 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 trial constrain interpretation. The non-randomized allocation means the Phase 1 and Phase 2 dose cohorts are not like-for-like comparison groups. Any difference in their posted safety figures could reflect participant characteristics, clinical circumstances, or other factors rather than maraviroc dose. The unmasked design may also affect event assessment or reporting. The registry record does not describe methods used to address these concerns.

The defined primary outcome is the number of adverse events following exposure, with a 1-year timeframe, but the posted safety results report participants affected by serious and other events. Total adverse-event counts, event-level details, and participant-level follow-up are not reported in the registry record. The serious-event terms list is empty, and death counts are not reported in the registry record. These gaps prevent a complete description of the specified primary outcome and limit interpretation of event frequency.

No statistical analyses are listed. The registry record does not report confidence intervals, hypothesis tests, adjusted comparisons, missing-data procedures, detailed analysis populations, multiplicity handling, or a sample-size justification. Although the primary population is described as patients receiving SCT, the record does not define the analysis set in further detail. The posted summaries therefore do not support conclusions about statistical precision or causal differences between cohorts.

The study description includes GVHD prevention as an aim and lists several secondary outcomes, but analyses for those outcomes are not reported in the registry record. The safety summaries alone cannot establish a prevention effect or provide a complete assessment of benefit and harm. These limitations concern what the record allows readers to conclude; they do not establish that unreported procedures or results were absent from other materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Maraviroc in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation — NCT00948753.
• Registry record last updated 2022-05-17; status last verified 2022-04.
• Results first posted 2022-05-17.
• 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.

18. Record Summary

NCT00948753 is a completed Phase 1 and Phase 2, non-randomized, unmasked, parallel-group study sponsored by Abramson Cancer Center at Penn Medicine. It enrolled 38 participants undergoing non-myeloablative allogeneic SCT. Maraviroc was administered twice daily alongside standard GVHD prophylaxis, with Phase 1 cohorts receiving 150mg or 300mg and a Phase 2 cohort receiving 300mg. The registry lists a start date of 2009-06 and primary completion of 2011-04.

The primary outcome was safety, defined as the number of adverse events following exposure to maraviroc over a 1-year timeframe. Posted safety results list participants affected by serious and other adverse events by cohort, but no inferential analyses are reported. The registry also lists secondary outcomes related to pharmacokinetics, chronic GVHD, early mortality, and relapse. Missing-data methods, detailed analysis populations, multiplicity procedures, and sample-size justification are not reported in the registry record.