Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC (NCT00923364), a na phase 2 study. The primary outcome is Days to Neutrophil Engraftment.

2. Clinical Question

3. Trial Design

This is a Phase 2, single-group study titled as a pilot and feasibility study of reduced-intensity hematopoietic stem cell transplantation for MonoMAC. The registry lists enrollment as 19 and status as completed. The recorded study start is 2009-05-07, and primary completion is dated 2014-06-12. Allocation is listed as not applicable, masking as none, and the study model as single-group. These features describe a nonrandomized study without a concurrent control group; they do not support a treatment-versus-control estimate.

The intervention combines transplantation with listed drugs and a procedure: cyclophosphamide, fludarabine, total body irradiation, allogeneic hematopoietic stem cells, and equine anti-thymocyte globulin. The group description includes recipients and healthy related donors and outlines several donor sources and matching categories. The record does not establish that outcomes for these donor and recipient roles should be interpreted as one homogeneous clinical population.

The primary outcome is days to neutrophil engraftment with a 30-day timeframe. The endpoint population description states that 10/19 were analyzed, and gives reasons for the remaining participants: 5 were healthy related donors, 1 was taken off study before transplant, and 3 had early deaths before outcome measurements could be evaluated. The primary endpoint's median and full range are not reported in the registry record.

The study lists secondary outcomes covering donor-cell percentage at last follow-up, acute and chronic graft-versus-host disease, overall survival, disease-free survival, and serious and non-serious adverse events. The record lists 7 outcome measures but 0 analyses. It does not report a statistical analysis plan, a sample-size justification, interim analyses, or inferential results for the primary endpoint.

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: 10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant \& 3 pts had early deaths (before outcome measurements could be evaluated)

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: Data were not collected separately for donors and recipients.

6. Primary Endpoint

The registry lists the primary outcome as Days to Neutrophil Engraftment, measured over 30 days.

Days to neutrophil engraftment measures the time until blood-cell recovery reaches a defined neutrophil threshold. The registry defines engraftment as a neutrophil count >0.5 x 10(9) cells/L for 3 consecutive days. Requiring the threshold to persist distinguishes sustained recovery from a transient reading. Recording the time in days makes this a time-to-event outcome: the event is engraftment, and each patient's time is measured until that event or until the observation period ends.

Engraftment is used as an early indicator of blood-cell recovery after transplantation. It is relevant to the study's stated focus on transplantation feasibility and safety, but it is not by itself a complete measure of longer-term health or transplant success. The registry lists the timeframe as 30 days and specifies the median and full range as the intended summary. A median describes the midpoint of observed event times; the full range describes the spread from the lowest to the highest observed time. Neither summary is reported in the registry record, so the endpoint's observed timing and variability cannot be assessed from the posted result.

The endpoint population entry states 10/19 analyzed and explains that 5 were healthy related donors, 1 participant was taken off study before transplant, and 3 had early deaths before outcome measurements could be evaluated. These exclusions matter because the endpoint summary pertains to an analyzed subset rather than everyone enrolled. The record does not describe an approach for incorporating participants without an evaluable engraftment time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines what statistical conclusions are available. This study is recorded as Phase 2 and single-group, with allocation not applicable and masking none. A single-group study can describe the outcomes observed in its enrolled or analyzed participants. It does not estimate a randomized contrast with a control arm, because no concurrent randomized control group is identified. This limits causal interpretation: an outcome can be reported as occurring in the study, but the design does not show what would have happened to a comparable group under another approach.

What does a median time-to-event endpoint describe?

Days to neutrophil engraftment is a time-to-event measure. The event is defined as reaching a neutrophil count >0.5 x 10(9) cells/L for 3 consecutive days. A median event time describes the time at which the event has occurred for the midpoint of the relevant observed distribution, when that median can be estimated. A full range gives the lower and upper observed event times. These summaries answer different questions: the median describes a central time, while the range describes the observed spread. They do not, on their own, quantify a treatment effect against a comparator.

Time-to-event methods are often useful when participants may have different follow-up durations or when some have not experienced the event by the end of observation. Such methods can account for incomplete event observation through censoring, when the censoring status and timing are known and the analysis uses an appropriate method. The registry's primary endpoint entry specifies a median and full range, but does not report a censoring method or the observed endpoint values. The record therefore does not support an assessment of how incomplete event observation was handled.

Why does the analyzed population matter?

The endpoint population entry says 10/19 were analyzed. It identifies 5 healthy related donors, 1 participant taken off study before transplant, and 3 participants with early deaths before endpoint measurements could be evaluated. The difference between enrollment and an endpoint analysis can affect how representative that analysis is of the enrolled group. In general, excluding participants after enrollment can create bias if the reasons for exclusion are related to prognosis or the outcome. That is a general methodological concern, not proof that bias occurred in this study. The registry does not report a missing-data strategy or further analysis of the excluded participants for this endpoint.

Deaths before an endpoint can be measured are especially relevant to interpretation of engraftment timing. Depending on the scientific question and prespecified method, death may be treated as a competing event, incorporated into a composite outcome, or handled in another defined way. The registry record does not report which approach, if any, was used. It would therefore be inappropriate to assume that the reported median accounts for early deaths; in fact, the median itself is not reported.

What can the event summaries establish?

The registry lists serious and non-serious adverse-event counts for the group named recipients and healthy related donors. Event counts and percentages are descriptive summaries. They do not establish causality, and terms may describe events that vary in clinical context. Without a comparison group, the summaries cannot estimate the excess risk attributable to the intervention. General statistical interpretation also depends on clear definitions of the population at risk, event ascertainment, observation period, and whether each participant can contribute more than one event. Details beyond the listed counts and terms are not reported in the registry record.

How should planning calculations be interpreted?

The stated planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the illustration uses the total number of events; for other outcomes, it uses participants per arm. Such calculations are hypothetical design planning, not evidence about the performance of the completed study and not observed power. They also do not turn this single-group study into a two-arm comparison. No numeric sample-size illustration or planning result is reported in the registry record.

In general, power is a design property calculated under assumptions about a target effect, variability, significance threshold, and analysis. A post hoc calculation using an observed estimate does not establish the probability that a finding is true. Here, the registry does not report the primary endpoint estimate or a sponsor analysis, so there is no basis for a numerical power interpretation. The sample-size assumptions should be read only as planning conventions, not as a finding from the trial.

The registry records 0 analyses and supplies no inferential statistics for the primary endpoint. A confidence interval, when reported, would communicate uncertainty around an estimate under the chosen statistical model; it would not eliminate limitations from an uncontrolled design or incomplete outcome information. A p-value, if reported, would quantify compatibility with a specified null model under the analysis assumptions, not the probability that the treatment works. Neither is available for the primary endpoint in this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including days to neutrophil engraftment as the primary outcome and secondary outcomes concerning donor-cell percentage at last follow-up, graft-versus-host disease, overall survival, disease-free survival, and adverse events. It records 0 analyses. The registry record does not report a prespecified statistical analysis plan, a hierarchy among secondary outcomes, or a method for adjusting for multiple comparisons.

Multiplicity arises when several outcomes or comparisons are tested. In general, making many separate statistical tests can increase the chance of at least one apparently unusual result even when there is no underlying effect. A prespecified hierarchy or adjustment can help define how such results should be interpreted. Since no inferential analyses are reported, and multiplicity procedures are not reported in the registry record, there is no basis for evaluating how this issue was addressed.

The primary endpoint population entry states 10/19 analyzed and gives reasons for participants who did not contribute an evaluable endpoint measurement. The record does not report imputation, a missing-data sensitivity analysis, or an analysis population definition beyond this endpoint-specific description. It also does not explain how early deaths were incorporated into any time-to-event analysis. These omissions limit assessment of whether the endpoint analysis represents all enrolled participants or how missing outcomes might affect its interpretation.

Information about interim analyses, stopping rules, and a sample-size justification is not reported in the registry record. Their absence from the record does not establish whether such planning occurred outside the registry; it means their methods and influence cannot be assessed from the posted information.

11. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death not associated with ctcae term::death nos (21.1%), alt, sgpt (serum glutamic pyruvic transaminase) (10.5%), dyspnea (shortness of breath) (10.5%), febrile neutropenia (10.5%), hypotension (10.5%).

The adverse-event summary names the group as recipients and healthy related donors, with 19 at risk for both serious and non-serious events. It reports serious adverse events affecting 12 participants and non-serious adverse events affecting 16 participants, with 4 deaths. These figures describe the registry's recorded safety experience for the named group. They are not a comparison with a separate control group and do not show that the intervention caused each event.

The most frequently listed serious-event term is “Death not associated with CTCAE term::Death NOS” at 21.1%. ALT, SGPT (serum glutamic pyruvic transaminase), dyspnea, febrile neutropenia, hypotension, and hypoxia are each listed at 10.5%. The record does not provide further detail in this summary about event timing, duration, clinical course, or attribution. The term describing death should not be treated as an additional count beyond the recorded deaths without further information.

Event terms are not necessarily mutually exclusive: a participant may experience more than one kind of event. The registry summary does not explain whether the listed percentages refer to participants, event occurrences, or another reporting convention. They should therefore be read as the posted term percentages, not added together or interpreted as distinct participant totals. The safety figures are descriptive and do not quantify comparative risk.

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

The record identifies a completed Phase 2 study evaluating reduced-intensity allogeneic hematopoietic stem cell transplantation for MonoMAC. Its primary endpoint is clinically interpretable in principle: time to sustained neutrophil recovery under a stated threshold. The record also gives a timeframe and explains which participants were included in the endpoint population. Those design and definition details help clarify what the intended outcome represents.

However, the registry does not report the primary endpoint's median or full range. It therefore does not show how long engraftment took among the analyzed participants or how much observed times varied. Although the objective refers to safety and efficacy, the available record does not contain a primary efficacy estimate or inferential analysis. The presence of an endpoint definition is not itself evidence of an outcome.

The safety summary reports adverse-event counts and terms for recipients and healthy related donors. These observations document events recorded in the study group, but do not prove that the transplant or a specific component caused them. With no concurrent control group, the record cannot establish a comparative effect on safety or engraftment. Nor can it separate the intervention's contribution from other influences on outcomes.

The study's single-group structure and endpoint exclusions also matter. The endpoint population description notes healthy donors, a participant removed before transplant, and early deaths whose measurements could not be evaluated. The registry does not report how missing outcomes or early deaths were addressed analytically. As a result, the scope of inference from any endpoint summary would require caution even if that summary were present.

Overall, the record is informative about the study question, intervention, design, outcome definitions, and reported safety counts. It does not provide enough statistical results to judge the magnitude or precision of the primary outcome, and it does not support a controlled comparison. These distinctions separate what the registry documents from conclusions it cannot establish.

13. Why This Trial Matters Statistically

This study raises statistical issues that are central to interpreting early transplantation research. A single-group pilot and feasibility design can describe whether participants underwent a procedure and what outcomes were recorded, but the absence of a concurrent control limits comparative inference. That distinction is important when a study objective uses terms such as safety and efficacy: the design and available results determine which parts of that objective can be evaluated statistically.

The endpoint definition is also important. Sustained neutrophil recovery is more specific than a single count above a threshold, and recording time to that event reflects both whether and when recovery is observed. Yet endpoint timing is only interpretable when the result, follow-up, and handling of participants without an evaluable event are clear. Here the registry identifies a partial analyzed population and early deaths, but does not report the endpoint summary or the method used to address these cases.

Safety reporting illustrates another general challenge. Serious and non-serious events are summarized in a group that includes recipients and healthy related donors. Those counts are useful as descriptive records, but without group-specific detail or a control comparison they cannot estimate attributable risk. The listed event terms also should not be treated as independent or mutually exclusive without further reporting detail.

Finally, the registry records outcomes but no analyses. That separation matters: listing an endpoint is not equivalent to publishing an estimate, and a completed study status does not supply missing statistical results. Clear reporting of analysis populations, missing-data handling, event methods, and uncertainty would be needed for a more complete statistical assessment.

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.

The primary limitation for statistical interpretation is that the registry record does not report the primary endpoint result. The intended summary is a median and full range for days to neutrophil engraftment, but neither is available. The record also lists 0 analyses, leaving no reported estimate, confidence interval, p-value, or hazard ratio for the primary outcome.

The single-group design has no concurrent control arm. This prevents a like-for-like estimate of outcomes relative to another treatment or control condition. Allocation is recorded as not applicable and masking as none. The registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The endpoint population is described as 10/19 analyzed, with healthy related donors, a participant taken off study before transplant, and early deaths listed as reasons that outcome measurements were not evaluated. The record does not report additional detail about endpoint-specific missingness, censoring, or how early deaths were handled. The group used for adverse-event summaries includes recipients and healthy related donors, which is a relevant qualification when interpreting its safety counts.

The registry lists secondary outcomes but does not report a statistical analysis plan, multiplicity strategy, interim analyses, or sample-size justification. It provides no further detail in the adverse-event summary about event attribution or observation timing. These limitations do not establish that the study methods were inadequate; they identify aspects that cannot be assessed from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC — NCT00923364.
• Registry record last updated 2020-03-12; status last verified 2020-03.
• Results first posted 2017-11-30.
• 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

NCT00923364 is a completed Phase 2 pilot and feasibility study of reduced-intensity hematopoietic stem cell transplantation for MonoMAC and GATA2 mutations. The registry lists enrollment as 19, a single-group model, allocation not applicable, and no masking. The recorded start date is 2009-05-07, with primary completion on 2014-06-12.

The primary endpoint is days to neutrophil engraftment, defined using a neutrophil count >0.5 x 10(9) cells/L for 3 consecutive days, with a 30-day timeframe. The registry states that 10/19 were analyzed and gives reasons for participants without evaluable endpoint measurements, but does not report the median or full range. It lists 7 outcome measures and 0 analyses.

The adverse-event summary reports 12 participants with serious events, 16 with non-serious events, and 4 deaths in the named group of recipients and healthy related donors. These are descriptive registry figures, not comparative estimates or evidence of causation.