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 Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease (NCT00448201), a non-randomized phase 2 study. The primary outcome is Treatment-related Mortality.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00448201 |
| Phase | Phase 2 |
| Condition | Chronic Myeloproliferative Disorders, Leukemia, Lymphoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 71 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UNC Lineberger Comprehensive Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes patients with hematologic cancer or other disease, including chronic myeloproliferative disorders, leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, and myelodysplastic syndromes. The official title focuses on patients with hematologic disorders who are ineligible or inappropriate for a more intensive therapeutic regimen. The number enrolled was 71.
Intervention
The treatment approach combined reduced-intensity busulfan and fludarabine with nonmyeloablative allogeneic hematopoietic stem cell transplantation. The registry also lists medicines and biological interventions including tacrolimus, methotrexate, antithymocyte globulin, sargramostim, and therapeutic allogeneic lymphocytes. The listed prophylaxis regimens differ in whether they include methotrexate and antithymocyte globulin, and in the number of ATG doses.
Comparator
There is no randomized control group. The registry identifies the study as non-randomized and single-group, while its regimen descriptions name four prophylaxis groups: methotrexate only, two doses of ATG plus methotrexate, two doses of ATG, and three doses of ATG. These descriptions do not establish that the groups were comparable or that their outcomes can be interpreted as a controlled treatment comparison.
Primary question
The primary endpoint asks how often treatment-related mortality occurred during the first 6 months, excluding deaths due to disease relapse. The registry record does not report a numerical result for this endpoint. It also does not report an estimate of the treatment effect or a statistical comparison between prophylaxis groups. The study therefore cannot answer a comparative question about which prophylaxis regimen has better outcomes from the information recorded.
3. Trial Design
This is a phase 2 clinical trial with non-randomized allocation, no masking, and a single-group model in the registry. Enrollment was 71, and the status is completed. The record lists a study start date of 2011-01-07 and a primary completion date of 2011-01-11. Those dates are registry milestones; they do not by themselves describe how long each participant was followed.
The treatment strategy involved reduced-intensity busulfan and fludarabine followed by donor stem cell transplantation. The registry lists four graft-versus-host disease prophylaxis descriptions: methotrexate alone; two doses of antithymocyte globulin (ATG) with methotrexate; two doses of ATG; and three doses of ATG. Although these descriptions identify different regimens, the record classifies the trial as single-group and non-randomized. It does not report how participants were assigned to the regimens or whether assignment depended on clinical characteristics.
The primary endpoint is treatment-related mortality during the first 6 months, excluding deaths due to disease relapse. Listed secondary outcomes include complete response, donor chimerism, disease-free survival, and graft-versus-host disease at specified post-transplant times. Numerical results for these outcomes and details of the statistical analysis are not reported in the registry record. The design and posted information therefore support a description of the study question and enrolled cohort, but not a randomized comparison or a quantified assessment of outcomes by regimen.
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 | All Trial Participants |
|---|---|
| STARTED | 71 |
| COMPLETED | 71 |
| NOT COMPLETED | 0 |
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 | All Trial Participants |
|---|---|---|
| Participants analysed | 71 | |
| Age, Continuous | years | 58 (28 to 69) |
| Sex: Female, Male: Female | Participants | 31 |
| Sex: Female, Male: Male | Participants | 40 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 9 |
| Race (NIH/OMB): White | Participants | 60 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 71 |
| Donor Types: HLA-matched related donor (MRD) | Participants | 37 |
| Donor Types: MUD or HLA-mismatched grafts | Participants | 34 |
| Comorbidity Index (CI) | units on a scale | 3 (0 to 8) |
| Disease Risk Index (DRI): Low | Participants | 9 |
| Disease Risk Index (DRI): Intermediate | Participants | 40 |
| Disease Risk Index (DRI): High | Participants | 19 |
| Disease Risk Index (DRI): Very High | Participants | 1 |
| Disease Risk Index (DRI): Undetermined | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Treatment-related Mortality, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is treatment-related mortality during the first 6 months. The registry defines it as the number of treatment-related deaths, excluding deaths due to disease relapse, and describes the measure as a percentage of participants. This endpoint focuses on deaths attributed to treatment within a specified follow-up period rather than on all deaths, regardless of cause.
In general, a defined mortality endpoint can help describe an important safety outcome after a treatment strategy. Its interpretation depends on the event definition, the time window, and how causes of death are classified. Excluding deaths due to relapse makes the attribution rule especially relevant: a reader needs to know how deaths were classified and who made that determination to assess the endpoint fully. Those adjudication details are not reported in the registry record.
The registry record does not give the observed percentage, event count for this endpoint, confidence interval, or an analysis result. It does report 44 deaths in the overall adverse-event summary, but does not specify how many met the primary endpoint definition or how many were due to relapse. The overall death count therefore cannot be substituted for the treatment-related mortality result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically important endpoint and its time window, but it does not report the numerical treatment-related mortality result. Without an event count or percentage for that endpoint, its observed frequency and statistical precision cannot be described. The overall adverse-event summary lists 44 deaths among the 71 participants at risk, but it does not provide cause-specific classification or establish which deaths occurred during the primary endpoint window. Those figures should not be treated as the primary endpoint result.
The record also lists serious adverse-event information for all trial participants: 71 were at risk and 7 were affected. The listed serious terms include graft vs host disease grade 4, fever, hypoxemia, graft failure, liver toxicity/hyperbilirubinemia, and CMV viremia. The listed percentages describe the registry entries, but do not provide enough context to infer individual risk over time, compare regimens, or determine whether an event was caused by a particular intervention.
Study design limits comparisons. The registry labels allocation as non-randomized and the model as single-group. It names several prophylaxis regimens, but does not report group-specific enrollment, baseline characteristics, endpoint results, or adjusted comparisons. Differences between participants receiving different regimens, if any, could reflect factors other than the regimen itself. The record explicitly does not support treating these groups as like-for-like controls.
Several secondary outcomes are named, including response, chimerism, disease-free survival, and graft-versus-host disease. Their numerical results, uncertainty estimates, and analysis details are not reported in the registry record. The status of completed indicates the study is recorded as completed; it does not supply the missing outcome estimates or show that every planned analysis was reported. Overall, the record documents the study’s question, design labels, enrolled cohort, and selected safety entries, but does not provide the numerical primary endpoint result needed to assess its frequency or precision.
9. Statistical Methods Explained
What does a percentage endpoint represent?
For a binary endpoint, each participant is classified according to whether the defined event occurred within the stated period. A percentage expresses the proportion of participants meeting that definition. Here, the event is treatment-related mortality during the first 6 months, with deaths due to disease relapse excluded. The result depends both on the event definition and on which participants are included in the denominator. The registry record does not report the observed endpoint percentage or the analysis population used to calculate it.
A confidence interval is a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; a wider interval generally indicates less precision. An interval for a proportion would depend on the event count, denominator, and method used. No confidence interval or interval method for the primary endpoint is reported in the registry record, so the precision of the estimate cannot be assessed.
Why does study design matter for comparisons?
Random allocation is one way to make treatment groups comparable, on average, with respect to measured and unmeasured factors. This trial is identified as non-randomized, and the registry classifies its model as single-group. Although four prophylaxis regimen descriptions are listed, the record does not describe a randomized comparison. A difference between regimen groups, if calculated, would not automatically show that the regimens caused the difference. Participant characteristics, clinical decisions, and other factors could also contribute.
Adjustment methods can account for measured differences between groups, but they cannot guarantee that all relevant differences have been addressed. The registry record does not report adjusted analyses, covariates, or a statistical analysis plan. It therefore does not establish whether any comparison was adjusted or what assumptions such an analysis would require.
What do significance levels and planning illustrations mean?
In general, a significance level is a threshold used when testing a specified statistical hypothesis. The sample-size planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe planning illustrations based on a fraction of the observed effect. These assumptions are not evidence that the trial was randomized, that it used those methods for its primary analysis, or that the registry reports an observed treatment effect. The registry record does not report a sample-size justification for the trial.
Planning sample sizes answer a hypothetical design question: how many participants might be needed under particular assumptions. They are not observed results, and they are not a measure of the probability that a completed study found a true effect. Since the primary endpoint estimate and the numerical planning illustrations are not reported in the registry record, no sample-size values or power conclusions can be interpreted from the record.
How should multiple outcomes be considered?
The record names a primary endpoint and several secondary outcomes, some assessed at more than one time point. In general, testing many outcomes or time points can increase the chance of at least one apparently notable result when all are considered together. Methods such as prespecifying a primary outcome or adjusting for multiple comparisons can address aspects of this issue, but the appropriate approach depends on the analysis plan. Multiplicity procedures and the analysis plan are not reported in the registry record.
Outcome-specific definitions and analysis populations also matter. For example, response, donor chimerism, disease-free survival, and graft-versus-host disease are distinct outcomes and cannot be interpreted as interchangeable measures. The registry lists these outcomes but does not report their numerical results or detailed methods. General statistical principles can explain what would be needed to interpret them, but cannot fill in those missing trial-specific details.
10. Multiplicity, Missing Data and Analysis Populations
The registry names a primary endpoint and several secondary outcomes. Some secondary outcomes are specified at multiple post-transplant times, including complete response, donor chimerism, disease-free survival, and graft-versus-host disease. Evaluating multiple outcomes or time points raises a general multiplicity question: without a prespecified strategy, the chance of at least one result appearing notable can increase. The registry record does not report a multiplicity adjustment, hierarchy among secondary outcomes, or a statistical analysis plan.
Missing-data methods are not reported in the registry record. The record does not describe how participants with incomplete follow-up, unavailable endpoint assessments, or other missing observations were handled. It also does not specify an analysis population for the primary or secondary endpoints. These details are important because the participants included in a particular analysis affect the interpretation of its estimate.
The registry gives enrollment as 71 and lists 71 participants at risk in the adverse-event summary. Those figures do not establish that all participants contributed data to every endpoint or follow-up time. Nor does the completed status establish that outcome data were complete. Without endpoint-specific denominators, missing-data handling, and analysis-population definitions, the completeness and comparability of outcome assessments cannot be evaluated from 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 |
|---|---|---|---|
| All Trial Participants | 7 | 71 | 9.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Trial Participants | 44 of 71 |
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 |
|---|---|
| All Trial Participants | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | All Trial Participants |
|---|---|---|
| Graft vs host disease grade 4 | Gastrointestinal disorders | 3 of 71 |
| Fever | Infections and infestations | 2 of 71 |
| hypoxemia | Blood and lymphatic system disorders | 1 of 71 |
| graft failure | Blood and lymphatic system disorders | 1 of 71 |
| liver toxicity/hyperbilirubinemia | Hepatobiliary disorders | 1 of 71 |
| CMV viremia | Infections and infestations | 1 of 71 |
| subdural hematoma | Vascular disorders | 1 of 71 |
| Failure to thrive | General disorders | 1 of 71 |
| elevated lipase | Gastrointestinal disorders | 1 of 71 |
| CMV pneumonia | Infections and infestations | 1 of 71 |
Serious events with the highest arm-level rate: graft vs host disease grade 4 (4.2%), fever (2.8%), hypoxemia (1.4%), graft failure (1.4%), liver toxicity/hyperbilirubinemia (1.4%).
The adverse-event summary lists all trial participants as the group at risk: 71 at risk and 7 affected. It also lists 44 deaths. These are separate entries in the registry summary; the record does not explain how the death count relates to the treatment-related mortality endpoint, whether deaths occurred within its 6-month window, or how deaths were attributed.
The serious-event terms listed include graft vs host disease grade 4 (4.2%), fever (2.8%), hypoxemia (1.4%), graft failure (1.4%), liver toxicity/hyperbilirubinemia (1.4%), and CMV viremia (1.4%). These are registry-listed percentages, not treatment-effect estimates. The record does not provide event timing, event-specific denominators, or a comparison between prophylaxis regimens. It also does not establish from these entries alone whether an event was caused by the transplant, a particular drug, the underlying disease, or another factor.
Safety entries should therefore be read as descriptive registry information. They do not establish comparative safety or provide a complete account of individual clinical courses.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2 study enrolled 71 participants and evaluated a reduced-intensity busulfan and fludarabine approach followed by donor stem cell transplantation. It identifies treatment-related mortality during the first 6 months, excluding deaths due to disease relapse, as the primary endpoint. The record also lists selected serious adverse-event terms and secondary outcomes.
It does not report the numerical result for the primary endpoint, its uncertainty, or the statistical analysis used to obtain it. The 44 deaths listed in the adverse-event summary are not a substitute for the defined primary endpoint because the record does not report their timing or cause classification. The serious-event entries likewise do not establish that a specific regimen caused an event or allow a comparison of regimens.
The study is identified as non-randomized and single-group. The regimen descriptions do not create a randomized control comparison, and the registry does not report group-specific outcome results. Any apparent difference between regimen groups would need to be interpreted cautiously, because treatment assignment and participant characteristics may be related. The record does not report methods that would quantify or address those potential differences.
These limitations do not negate the descriptive information in the record. They define what can be concluded from it: the study question, design labels, enrollment, listed outcomes, and selected safety information are documented, while the numerical primary endpoint result and analysis details are not reported in the registry record. No conclusion about comparative effects or treatment benefit follows from the information recorded.
13. Why This Trial Matters Statistically
This study illustrates why a clearly defined endpoint is only one part of a statistical result. The record specifies treatment-related mortality, a 6-month window, and an exclusion for deaths due to disease relapse. Those details define the intended event, but an event count or percentage and an account of uncertainty are also needed to understand how often it occurred and how precisely it was estimated. The registry record does not report those primary endpoint results.
It also highlights the distinction between a set of treatment descriptions and a valid comparative design. The record lists multiple prophylaxis regimens, while identifying the trial as non-randomized and single-group. Without random allocation or reported methods that address group differences, regimen-specific comparisons cannot automatically be interpreted as causal. This is especially important when the record does not provide group sizes, participant characteristics, or outcome estimates by regimen.
Finally, a completed study record can still leave key statistical questions unanswered. The record names secondary outcomes and provides selected serious adverse-event entries, but does not report the outcome analysis methods, missing-data handling, or multiplicity strategy. These omissions limit evaluation of both the magnitude and precision of results. The example underscores the value of registry records that report endpoint-specific counts, denominators, uncertainty, analysis populations, and methods alongside study design information.
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 endpoint result is not reported in the registry record. The record gives its definition and time window but no event count, percentage, confidence interval, or analysis details. The overall count of 44 deaths cannot resolve this limitation because the record does not provide timing or cause-of-death classification for that count.
The trial is designated non-randomized and single-group, yet the registry describes several prophylaxis regimens. It does not report how participants entered those regimens, the number in each group, or whether baseline characteristics differed. Accordingly, the listed regimen descriptions do not support a like-for-like comparison. Comparative outcome estimates and adjusted analyses are not reported in the registry record.
Other details needed for interpretation are also absent. The record does not report the statistical analysis plan, endpoint-specific analysis populations, missing-data methods, multiplicity procedures, or adjudication methods for treatment-related deaths. It lists secondary outcomes but does not report their numerical results. The listed serious adverse-event percentages do not include event-specific timing or denominators, and the record does not explain causal attribution.
These limitations concern what can be interpreted from the registry record; they do not establish that unreported analyses or information were absent from all study documentation. The record itself does not provide the details needed to assess those matters.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease — NCT00448201.
- Registry record last updated 2017-05-30; status last verified 2017-05.
- Results first posted 2017-05-30.
- 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.
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18. Record Summary
The record describes a completed phase 2, non-randomized, single-group study of reduced-intensity busulfan and fludarabine followed by donor stem cell transplantation. Enrollment was 71. The registry lists several graft-versus-host disease prophylaxis regimens and identifies treatment-related mortality during the first 6 months, excluding deaths due to disease relapse, as the primary endpoint.
The record names secondary outcomes involving response, donor chimerism, disease-free survival, and graft-versus-host disease. Its adverse-event summary lists 7 affected participants among 71 at risk and 44 deaths, alongside serious-event terms and percentages. The numerical primary endpoint result, endpoint-specific analysis details, and secondary outcome results are not reported in the registry record. Because allocation was non-randomized and the study is classified as single-group, the listed regimens should not be interpreted as randomized comparison arms.