This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide (NCT00800839), a na phase 2 study. The primary outcome is Cumulative Incidence of Grade II to IV Acute GVHD.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00800839 |
| Phase | Phase 2 |
| Condition | Hematologic Diseases, Leukemia, Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 56 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with hematologic malignancies receiving an allogeneic stem cell transplant. The registry lists hematologic diseases, leukemia, lymphoma, and myeloma among the conditions of interest. The enrollment was 56.
Intervention
A regimen of busulfan and fludarabine followed by cyclophosphamide after transplantation. The stated purpose was to study whether post-transplant cyclophosphamide could help prevent graft-versus-host disease (GVHD), while also studying the safety of the drug combination.
Comparator
There was no separate comparison group in the trial design. The registry identifies a single-group study, with allocation listed as not applicable and no masking. The regimen was not compared with a randomized control arm in this study.
Primary question
What is the cumulative incidence of grade II to IV acute GVHD within 100 days after transplantation, accounting for death or disease progression before GVHD as competing risks? The registry names this as the primary outcome but does not report its estimated incidence or confidence interval.
This is a question about the observed outcome in a treated group, not a randomized comparison of treatment strategies. Without a concurrent control group, the study cannot directly estimate how the outcome would differ under another regimen. The clinical context is allogeneic transplantation for hematologic malignancies, where GVHD is a condition in which transplanted tissue attacks the recipient's body. The registry describes prevention of GVHD and safety as study aims, but the numerical primary outcome is not reported in the registry record. That absence limits the conclusions that can be drawn from the posted record: the study question is clear, but its primary result cannot be assessed from the record's outcome information.
3. Trial Design
The registry describes a phase 2, single-group study of busulfan, fludarabine, and cyclophosphamide in patients with hematologic malignancies undergoing transplantation. The enrollment was 56. Allocation is listed as not applicable, masking as none, and the study model as single group. There is no randomized comparator arm in the design, so any outcome describes the enrolled group rather than a contrast between assigned treatments.
The intervention is titled busulfan and fludarabine followed by post-transplant cyclophosphamide. The arm description includes busulfan and fludarabine dosing details, but its description of cyclophosphamide is truncated in the registry record. The complete regimen cannot therefore be reconstructed from that arm description. The brief summary states that the study aimed to learn whether cyclophosphamide given after busulfan and fludarabine could help prevent GVHD, and that the safety of the combination would also be studied.
The registry lists the study as completed. Its recorded start was 2008-09 and its primary completion was 2015-07. The primary outcome was cumulative incidence of grade II to IV acute GVHD within 100 days after transplant. Secondary outcomes include rate of engraftment, 2-year progression-free survival, and 2-year overall survival. These outcome names identify what was planned for assessment, but the registry record does not report numerical results for them.
A single-group phase 2 design can describe outcomes and safety observations in the treated participants. It does not, by itself, separate regimen effects from other influences on outcome, such as underlying disease, participant characteristics, or care practices. Because allocation is not applicable and there is no control group, comparisons with other studies would also require caution: populations, outcome definitions, follow-up, and analysis methods may differ. The registry does not report a detailed statistical analysis plan, sample-size justification, or further design rationale.
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
| Stage | Busulfan + Fludarabine + Cyclophosphamide |
|---|---|
| STARTED | 56 |
| COMPLETED | 49 |
| NOT COMPLETED | 7 |
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.
| Characteristic | Unit | Busulfan + Fludarabine + Cyclophosphamide |
|---|---|---|
| Participants analysed | 49 | |
| Age, Continuous | years | 61 (39 to 72) |
| Sex: Female, Male: Female | Participants | 21 |
| Sex: Female, Male: Male | Participants | 28 |
| Region of Enrollment: United States | participants | 49 |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Incidence of Grade II to IV Acute GVHD, measured over 100 days post transplant.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of incidence |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the cumulative incidence of grade II to IV acute GVHD within the first 100 days after transplantation. The registry defines the event as grade 2 to 4 GVHD diagnosed during that period. It also specifies that death or disease progression before a GVHD diagnosis was treated as a competing risk in estimating the incidence.
Cumulative incidence describes the probability of observing the event of interest over a specified period while recognizing that some participants may experience another event that prevents the event of interest from being observed in the same way. In this setting, a participant who dies or has disease progression before GVHD is diagnosed cannot simply be treated as though that competing event had not occurred. Accounting for competing risks is therefore relevant to interpreting the frequency of GVHD in the enrolled group.
The endpoint focuses on an early post-transplant period and on clinically graded acute GVHD. The registry specifies a 95% confidence interval as the measure of dispersion for the primary outcome. However, neither the estimated cumulative incidence nor the endpoints of its confidence interval are reported in the registry record. The endpoint definition is available, but its numerical result and precision cannot be evaluated from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry gives a defined primary question: the cumulative incidence of grade II to IV acute GVHD within 100 days after transplant, with death or disease progression before diagnosis accounted for as competing risks. It does not give the numerical estimate or its 95% confidence interval. Consequently, the posted record does not establish how often the primary outcome occurred in the enrolled group, nor how precisely that frequency was estimated.
This distinction matters. An endpoint definition tells readers what investigators intended to measure; it is not itself an outcome result. The absence of a posted estimate should not be read as evidence that no acute GVHD occurred, that the incidence was low, or that the regimen prevented GVHD. It means that the registry record does not report the primary result. The same caution applies to the listed secondary outcomes: engraftment rate, 2-year progression-free survival, and 2-year overall survival are named, but their numerical results are not included in the record.
The study enrolled 56 participants in a single group. Outcomes in that group could describe what happened among the enrolled participants, but the design does not offer a randomized control group for estimating a treatment contrast. A before-and-after or external comparison cannot be inferred from the design details in the registry. Even if a numerical rate were available, it would be an observed rate in this study population, not an estimate of the difference caused by the regimen relative to a concurrent alternative.
The stated 95% confidence interval would ordinarily communicate uncertainty around the estimated cumulative incidence. Without the estimate and interval, neither the outcome's scale nor its statistical precision can be judged. Sample size alone cannot replace those results: the enrolled number does not show the observed event frequency, and it does not establish that an effect was detected or ruled out.
The safety record contains adverse-event summaries for the single group, including counts of participants affected by serious and other adverse events and a list of serious event terms. These observations describe events recorded in the group. They do not by themselves establish that the regimen caused each event, and the listed serious-event terms cannot be interpreted as the primary endpoint. The record does not provide all details needed to assess event timing, attribution, or the denominator used for each term percentage.
Overall, the registry record supports a description of the intended question, design, enrollment, and some safety counts. It does not support a conclusion about the size or precision of the primary outcome, nor a causal claim that the regimen changed GVHD risk. Those limits follow from missing outcome results and the absence of a randomized comparison, rather than from a statistical test showing no effect.
9. Statistical Methods Explained
What does cumulative incidence mean?
General statistical explanation. Cumulative incidence is used to describe the probability of an event occurring over a defined period. It takes account of the fact that participants may have different follow-up times and that an event can occur before the end of observation. In this trial, the event of interest was grade II to IV acute GVHD within 100 days after transplant. The registry names the measure as cumulative incidence, but does not report its numerical estimate.
The registry explicitly identifies death or disease progression before GVHD diagnosis as competing risks. A competing risk is an event that changes whether the event of interest can subsequently be observed. Treating such an event as ordinary loss to follow-up can answer a different question, because ordinary censoring generally represents incomplete observation rather than an event that precludes observing the outcome in the same way. The registry's endpoint description says that these competing risks were considered in estimating acute GVHD incidence. Details of the specific estimator are not reported in the registry record.
How should the confidence interval be read?
General statistical explanation. A confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used. Its width reflects precision: a narrower interval indicates greater precision than a wider interval, all else equal. It does not show the range of individual participant outcomes, and it does not guarantee that the true value lies inside a particular realized interval. The primary endpoint is specified with a 95% confidence interval, but the interval itself and the point estimate are not reported in the registry record. Therefore, the precision of the primary outcome cannot be assessed.
A confidence interval would not substitute for a comparison group. In a single-group study, an interval around the observed cumulative incidence would quantify uncertainty about that group's outcome under the analysis method. It would not directly estimate a contrast against another treatment. Nor would the interval alone establish whether any observed outcome was caused by the regimen. These are separate questions involving study design and assumptions beyond interval estimation.
What can the single-group design estimate?
General statistical explanation. A single-group study can describe outcomes among participants receiving the study regimen. Without a concurrent control group, it cannot directly compare those outcomes with what would have occurred under a different regimen in otherwise comparable participants. Random allocation can help balance measured and unmeasured characteristics between groups; this study does not report such an allocation because its design is single group and allocation is listed as not applicable.
That does not make descriptive outcomes meaningless. They can characterize the enrolled group and inform further questions, provided the outcome estimates and methods are available. But comparisons with external populations require attention to differences in eligibility, disease mix, follow-up, outcome definitions, and other factors. The registry record does not report an adjusted comparative analysis, and it lists zero analyses. No inferential comparison should be attributed to this record.
What does the endpoint's time window contribute?
The primary outcome is limited to the first 100 days after transplant. A time window makes the event definition specific: the primary question concerns acute GVHD diagnosed during that period, not all GVHD at any later time. The registry also lists 2-year progression-free survival and 2-year overall survival as secondary outcomes. Those longer-term outcomes address different events and time horizons from the primary endpoint. Their numerical results and analysis details are not reported in the registry record.
General statistical explanation. Time-to-event outcomes can account for when events occur and for differing lengths of observation. A rate or probability by a fixed time point is not interchangeable with a simple event count, because follow-up and competing events matter. The record describes a cumulative-incidence endpoint with competing risks, but does not report enough statistical detail to assess the full calculation, handling of incomplete follow-up, or any assumptions about observation.
What can planning calculations say?
General statistical explanation. Sample-size calculations depend on design assumptions, such as the target effect, allocation, significance level, and statistical method. A planning illustration based on an observed effect is not the same as a prospective sample-size justification, and a sample-size calculation does not show that an effect was detected. It is not observed power. The registry record does not report the trial's own sample-size justification or its detailed design assumptions.
The record also does not report a detailed statistical analysis plan, interim analyses, or whether any adjusted analyses were planned. These omissions prevent readers from checking whether the posted outcome was analyzed according to a prespecified plan. More importantly, the primary estimate itself is not reported, so there is no estimate or interval to interpret statistically. The endpoint definition, single-group structure, and stated competing risks are the main methodological details available for understanding the intended primary analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures and identifies cumulative incidence of grade II to IV acute GVHD as the primary outcome. It names engraftment rate, 2-year progression-free survival, and 2-year overall survival among the secondary outcomes. The record does not report numerical results for these named outcomes, nor does it describe how multiple outcome analyses were handled.
General statistical explanation. Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are interpreted without an appropriate plan, the chance of a seemingly notable result arising by chance can increase. A statistical plan may define a primary endpoint, specify how secondary findings will be interpreted, or use an adjustment procedure. Whether any multiplicity adjustment was planned or used is not reported in the registry record; it would be inappropriate to infer either adjustment or no adjustment from the available information.
The record does not report how missing outcome data were handled, whether participants with incomplete follow-up were included in particular analyses, or which analysis populations were used. It also does not describe imputation, censoring rules beyond the stated competing-risk treatment, or sensitivity analyses. These details can affect interpretation because missing observations and differences between enrolled and analyzed participants may influence estimates.
The registry lists zero analyses. That means the record does not present analysis-level results from which to assess these issues. The primary outcome's point estimate and 95% confidence interval are also absent. As a result, readers cannot evaluate the numerical findings, their precision, or the analysis choices that produced them. Any specific claim about multiplicity correction, missing-data methods, or analysis populations would go beyond what is reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Busulfan + Fludarabine + Cyclophosphamide | 39 | 56 | 69.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Busulfan + Fludarabine + Cyclophosphamide | 54 of 56 |
Most frequent serious adverse event terms
| Event term | Organ system | Busulfan + Fludarabine + Cyclophosphamide |
|---|---|---|
| Death | General disorders | 39 of 56 |
| Graft Failure due to Rejection | Immune system disorders | 4 of 56 |
| Infections Bacterial | Infections and infestations | 4 of 56 |
| GI GvHD | Gastrointestinal disorders | 3 of 56 |
| Liver GvHD | Hepatobiliary disorders | 3 of 56 |
| Infections Fungal | Infections and infestations | 3 of 56 |
| BK virus associated hemorrhagic cystitis | Infections and infestations | 2 of 56 |
| Infections Viral | Infections and infestations | 2 of 56 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 2 of 56 |
| Cardio-renal syndrome | Cardiac disorders | 1 of 56 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Busulfan + Fludarabine + Cyclophosphamide |
|---|---|---|
| Mucositis | Gastrointestinal disorders | 48 of 56 |
| Nausea | Gastrointestinal disorders | 48 of 56 |
| Infections Bacterial | Infections and infestations | 36 of 56 |
| Infections Viral | Infections and infestations | 33 of 56 |
| Neutropenic fevers | Infections and infestations | 30 of 56 |
| Skin GVHD | Skin and subcutaneous tissue disorders | 25 of 56 |
| BK virus associated hemorrhagic cystitis | Infections and infestations | 24 of 56 |
| Diarrhea | Gastrointestinal disorders | 21 of 56 |
| Fevers due to ATG | General disorders | 19 of 56 |
| Fluid overload | Blood and lymphatic system disorders | 17 of 56 |
Serious events with the highest arm-level rate: death (69.6%), graft failure due to rejection (7.1%), infections bacterial (7.1%), gi gvhd (5.4%), liver gvhd (5.4%).
The safety record lists one group, with 56 participants at risk for serious adverse events and 39 affected. For other adverse events, it lists 56 at risk and 54 affected. These are participant-level counts in the registry's group summary; they are not counts of the total number of individual events. A participant may experience more than one event, and the record does not provide event-level totals in the information summarized.
The listed serious adverse-event terms include Death at 69.6%, Graft Failure due to Rejection at 7.1%, Infections Bacterial at 7.1%, GI GvHD at 5.4%, Liver GvHD at 5.4%, and Infections Fungal at 5.4%. The registry record does not specify the denominator for these term percentages in the information available. They should not be converted into participant counts or interpreted as percentages of all enrolled participants without that denominator.
These safety summaries do not establish that the regimen caused each event. The record does not provide the event timing, participant-level overlap among terms, or attribution details needed for a fuller interpretation. The serious adverse-event term Death is not the same measure as the primary endpoint of cumulative incidence of acute GVHD. Safety counts and outcome estimates answer different questions, and the numerical primary outcome is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes the study's intended question and gives several design details. It describes a phase 2 single-group study of busulfan and fludarabine followed by post-transplant cyclophosphamide, with enrollment of 56 participants. The primary endpoint is defined as cumulative incidence of grade II to IV acute GVHD in the first 100 days after transplant, accounting for death or disease progression before diagnosis as competing risks. This is useful information about what investigators set out to assess.
However, the endpoint result is not reported in the registry record. There is no numerical incidence estimate or 95% confidence interval to evaluate. The record also names secondary outcomes without reporting their results. Thus the posted information cannot establish the observed frequency of acute GVHD, the precision of that estimate, or the outcome of the listed longer-term measures.
The design further limits what any observed outcome could mean. Because the study has one group and no randomized comparator, it cannot directly estimate how outcomes differ from another regimen. An outcome in the enrolled group would be descriptive; it would not by itself prove that the regimen caused a particular benefit or harm. The record's safety summaries describe affected participants and serious event terms, but do not establish causation for each event.
These limitations should be kept distinct. The absence of a primary result is a reporting limitation in the registry record. The absence of a comparison group is a design limitation for causal contrasts. Neither should be mistaken for evidence that the intervention succeeded or failed. The appropriate reading is that the record identifies an important clinical outcome and the study structure, while leaving the central numerical result and much of the analysis detail unavailable.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why endpoint definitions and design structure both matter. The primary outcome is not simply a count of GVHD events: it is a cumulative-incidence measure over a defined period, with death or disease progression before diagnosis treated as competing risks. That specification signals that events preventing observation of GVHD are relevant to estimating its occurrence. A reader who ignored that feature could misunderstand what the intended estimate represents.
The single-group design is equally important. A well-defined outcome can describe what happened in the enrolled group, but it does not create a treatment comparison. The record lists no randomized comparator, so a numerical result, if reported, would not by itself answer how outcomes would differ under an alternative regimen. This distinction between estimating an outcome and estimating a causal contrast is central to interpreting clinical-trial results.
The record also illustrates the value of reporting estimates with measures of precision. Naming a 95% confidence interval indicates that uncertainty was intended to accompany the primary estimate, but neither the estimate nor the interval is reported. Without them, readers cannot assess the scale or precision of the primary finding. Enrollment alone cannot fill that gap.
Finally, outcome reporting, safety reporting, and statistical methods are separate parts of interpretation. The record includes adverse-event summaries, but these do not replace the missing primary result or establish causation. It also does not describe important analysis details such as missing-data handling or multiplicity. Recognizing what is documented, what is absent, and what the design can support helps prevent stronger conclusions than the record warrants.
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 principal limitation for interpreting the trial from the registry record is that the primary endpoint's numerical result is absent. Although cumulative incidence of grade II to IV acute GVHD within 100 days and a 95% confidence interval are specified, neither the estimate nor its interval is reported. Numerical results for the listed secondary outcomes are also not reported in the registry record.
The study is single group, with allocation listed as not applicable and masking as none. It has no randomized control group, so it cannot provide a direct randomized comparison with another regimen. This limits causal interpretation even if descriptive results are available. The enrollment of 56 describes the study size but does not provide the missing event estimate or its precision.
The registry record does not report the trial's sample-size justification, detailed statistical analysis plan, interim analyses, or analysis populations. It does not describe missing-data procedures, sensitivity analyses, or multiplicity handling. These omissions leave uncertainty about the planned and executed analysis beyond the endpoint's stated competing-risk approach.
The intervention description is also incomplete: the arm description is truncated during its account of cyclophosphamide. The record therefore does not allow the full regimen to be reconstructed from that description. The safety summary gives participant counts and selected serious-event terms, but the term-percentage denominators, timing, attribution, and overlap among events are not reported in the available record. These limitations restrict both reproducibility and interpretation without establishing that any specific outcome or analysis was favorable or unfavorable.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide — NCT00800839.
- Registry record last updated 2016-09-19; status last verified 2016-07.
- Results first posted 2016-09-19.
- 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.
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18. Record Summary
The registry identifies NCT00800839 as a completed phase 2, single-group study of busulfan and fludarabine followed by post-transplant cyclophosphamide in patients with hematologic malignancies. Enrollment was 56. The recorded study start was 2008-09, and primary completion was 2015-07. Allocation was listed as not applicable and masking as none.
The primary outcome was cumulative incidence of grade II to IV acute GVHD within 100 days after transplant, with death or disease progression before diagnosis treated as competing risks. The registry specifies a 95% confidence interval but does not report the estimate or interval. Listed secondary outcomes include engraftment rate, 2-year progression-free survival, and 2-year overall survival; their numerical results are not reported in the registry record.
The safety summary lists 39 of 56 participants affected by serious adverse events and 54 of 56 affected by other adverse events. The record does not report the primary outcome result, a randomized comparison, or detailed analysis methods needed to support broader conclusions.