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-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies (NCT00943319), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00943319 |
| Phase | Phase 1, Phase 2 |
| Condition | Leukemia, Lymphoma, Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Chicago |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced hematologic malignancies. The listed conditions are leukemia, lymphoma, and myeloma. The study summary also identifies advanced acute myeloid leukemia and myelodysplastic syndromes as the population for evaluating disease-free and overall survival. The primary endpoint description states that 36 patients were in the phase I portion; the total enrollment is 50.
Intervention
Intravenous busulfan in combination with fludarabine as a conditioning regimen for transplantation with in-vivo T-cell depletion. The listed interventions also include Campath and stem cell transplant.
Comparator
No separate comparator is listed. The registry record describes a single-group study, with allocation recorded as not applicable and no masking.
Primary question
What is the maximum tolerated area under the curve of intravenous busulfan when used with fludarabine as conditioning for transplantation with in-vivo T-cell depletion? The record also states aims to evaluate overall and disease-free survival and potential pharmacogenomic determinants of toxicity and efficacy.
The central statistical question is therefore dose and tolerability estimation within a treatment group, rather than an estimate of the difference between two treatment strategies. Such a study can describe the experience of participants receiving the regimen and can support assessment of a dose target under the study conditions. It cannot, on its own, estimate how outcomes would have differed under an alternative regimen or without the regimen.
The registry record lists overall survival and disease-free survival as secondary outcomes, but does not report their estimates, definitions, or event counts. It also does not report the maximum tolerated dose value. Thus, the stated aims and endpoint are identifiable, while the numerical results needed to answer them are not reported in the registry record.
3. Trial Design
This is a phase I-II, completed, single-group study sponsored by the University of Chicago. The registry record lists enrollment of 50 and describes the study as having no masking. Allocation is recorded as not applicable, consistent with the absence of a randomized comparison group. The listed study dates are 2012-03 for the start and 2017-12 for primary completion.
The regimen combines intravenous busulfan and fludarabine for conditioning before allogeneic stem cell transplantation with in-vivo T-cell depletion. Campath and stem cell transplant are also listed as interventions. The arm description identifies busulfan and fludarabine, but the record does not describe a separate control arm or an alternative treatment strategy.
The primary outcome is maximum tolerated dose, expressed as an area-under-the-curve measure for intravenous busulfan in combination with fludarabine. The primary outcome description specifies that the 36 patients associated with this endpoint refer to the phase I portion only. Overall survival and disease-free survival are listed as secondary outcomes. The study summary additionally states aims to investigate pharmacogenomic determinants of toxicity and efficacy; the registry record does not provide results for those aims.
Although the study is marked completed, completion status does not itself establish that every planned endpoint has a posted result. No numerical maximum tolerated dose, survival estimate, or pharmacogenomic finding is reported in the registry record. The record also does not describe the dose-assignment procedure, eligibility criteria in detail, follow-up completeness, or the precise analysis populations for the secondary outcomes. Those omissions limit reconstruction of how the study was conducted and how its outcomes were analyzed.
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 and Fludarabine |
|---|---|
| STARTED | 50 |
| COMPLETED | 49 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Busulfan and Fludarabine |
|---|---|
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: The 36 patients refer to the phase I portion of the study only.
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 and Fludarabine |
|---|---|---|
| Participants analysed | 50 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 46 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 31 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 39 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 |
| Region of Enrollment: United States | participants | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose, measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mmol-min/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of intravenous busulfan when combined with fludarabine as a conditioning regimen for transplantation with in-vivo T-cell depletion. It is described as an area under the curve (AUC), a measure that represents drug exposure over time. AUC can be used to characterize systemic exposure rather than relying only on a dose amount; in a dose-finding context, exposure may be the quantity being targeted.
In general, a maximum tolerated dose endpoint is used in early-phase research to identify a dose or exposure considered tolerable under a study’s prespecified rules. The exact meaning depends on how toxicity is defined, how observation periods are set, and how dose decisions are made. Those operational details are not reported in the registry record, so the endpoint’s decision rule cannot be reconstructed from the record.
The registry record gives the endpoint unit as mmol-min/L in the endpoint listing, while its description gives µmol-min/L. This internal unit difference is not resolved in the record. It also identifies 36 patients for the phase I portion, distinct from the overall enrollment of 50. Most importantly, the numerical AUC value for the maximum tolerated dose is not reported in the registry record. The endpoint can therefore be described, but its observed result cannot be interpreted quantitatively.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The information in the registry record establishes the broad design and intended outcomes: this was a phase I-II, single-group study of busulfan-fludarabine conditioning followed by T-cell-depleted allogeneic stem cell transplantation. Its primary endpoint concerns busulfan exposure and tolerability. Overall survival and disease-free survival are named as secondary outcomes. The record does not include the observed maximum tolerated dose or survival results, so no numerical conclusion about those outcomes can be drawn from the posted information.
Because there is no separate comparator group, the study is not a randomized treatment comparison. Any observed events or outcomes within the group would describe participants treated under the study regimen, not the difference between that regimen and another approach. Even complete outcome counts from a single group would not by themselves establish what would have happened to comparable participants under a different strategy. Differences in patient characteristics, disease status, supportive care, and follow-up could matter in a comparison across studies or settings.
The registry record reports 50 enrolled participants and specifies that 36 patients refer to the phase I portion for the primary endpoint. These figures describe the enrollment and endpoint population stated in the record; they do not establish how many participants contributed to each other analysis. The record does not report the analysis populations, losses to follow-up, or the number of participants with evaluable outcome data. The total enrollment should not be treated as the denominator for every endpoint without that information.
Deaths are reported as 45 in the adverse-event information, but the registry record does not give the timing, causes, follow-up window, or relationship to treatment. This count cannot substitute for an overall-survival analysis, which requires a defined time origin, follow-up information, and an account of censoring. Similarly, listing disease-free survival as an outcome does not reveal the event definition, estimate, or precision.
The safety information also gives 49 participants at risk and 1 affected for serious events, and 49 at risk and 1 affected for other events. These are descriptive counts, not a comparative safety estimate. The record’s listed serious term Sepsis is 2.0%, but it does not provide enough context to connect that percentage to a specific analysis denominator or observation period. The available information is therefore best read as a limited registry snapshot: it identifies the study’s aims and some reported counts, but it does not provide the outcome estimates required for a fuller assessment.
9. Statistical Methods Explained
General statistical explanation: A phase I dose-finding endpoint and a survival endpoint answer different statistical questions. A maximum tolerated dose analysis concerns the relationship between dose or exposure and toxicity under specified rules. A survival analysis concerns the time until a defined event, while accounting for differing follow-up. Naming both types of endpoints does not mean that the same method or participant set was used for each.
What can a maximum tolerated dose tell us?
In general, a maximum tolerated dose is an operational target determined by a protocol-defined toxicity rule. A dose-finding method needs a definition of what counts as a dose-limiting toxicity, the period in which it is assessed, and the procedure for assigning or changing dose. Different rules can lead to different dose estimates, even when studying the same regimen. The registry record identifies an AUC-based endpoint and says the primary endpoint population is the 36 patients in the phase I portion, but it does not report the toxicity rule, dose-assignment method, dose levels, or observed AUC result. The method used to reach an estimate is therefore not reported in the registry record.
Why is the AUC unit important?
The endpoint is described in terms of drug exposure, and the record gives two different unit expressions: mmol-min/L in the endpoint listing and µmol-min/L in the description. Units are necessary to interpret the scale of a measured exposure. Without a resolved unit and the numerical endpoint value, the result cannot be compared or interpreted quantitatively. No conversion should be inferred from the registry record.
What do survival outcomes require?
General statistical explanation: Overall survival and disease-free survival are time-to-event outcomes. Their interpretation depends on a clearly specified starting point, an event definition, the follow-up period, and the treatment of participants whose event status is not observed by the end of follow-up. Censoring is the statistical handling of participants whose event time is not known beyond their last observed follow-up. A survival curve or summary estimate can incorporate such incomplete follow-up, but it needs the underlying event and censoring information and a stated analysis method.
The registry record lists overall survival and disease-free survival, but does not report their estimates, definitions, follow-up summaries, event counts, or analysis method. It therefore does not support interpretation of the precision or time pattern of either outcome. The death count in the adverse-event information is not an alternative to a survival analysis: it lacks the timing and follow-up context needed to describe survival over time.
How should a single-group design be interpreted?
General statistical explanation: A single-group study can characterize outcomes among participants who receive a regimen. It does not directly estimate a treatment contrast, because there is no concurrent comparison group to show the outcome under an alternative. A comparison with an external group would require additional assumptions about comparability, which are not established by the registry record. Accordingly, the listed design supports a within-study description, not a randomized estimate of relative benefit or harm.
What do the planning illustrations represent?
General statistical explanation: Sample-size planning asks how many participants or events a future design might need under specified assumptions. The planning assumptions described in the registry material use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe a planning illustration, not the design of this single-group trial. They do not constitute observed power, and they do not establish the study’s original sample-size justification. The record does not report a protocol-based sample-size rationale.
For time-to-event planning, the stated approach concerns a total number of events; for other planning illustrations, the quantity is participants per arm. These are planning conventions rather than observed trial outcomes. No particular planning estimate or effect value is reported in the registry record, so none can be interpreted as an observed result.
What uncertainty and multiplicity information is missing?
General statistical explanation: A confidence interval describes the range of values reasonably compatible with an estimate under a statistical model and sampling assumptions. It communicates precision as well as the point estimate. No confidence interval for the primary endpoint or the secondary outcomes is reported in the registry record. The record also does not report a statistical analysis plan, interim-analysis procedures, or methods for addressing multiple outcomes. When several outcomes are examined, multiplicity can affect how strongly individual findings should be interpreted; the appropriate approach depends on the study’s prespecified aims and analysis plan, which are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry record names a primary endpoint, maximum tolerated dose, and lists overall survival and disease-free survival as secondary outcomes. It also describes aims to evaluate potential pharmacogenomic determinants of toxicity and efficacy. However, it does not report a statistical analysis plan, a hierarchy among the secondary or pharmacogenomic aims, or a method for controlling or interpreting multiplicity. It is therefore not possible to determine whether analyses were prespecified as confirmatory or exploratory, or how any multiplicity was handled.
Missing-data procedures are not reported in the registry record. The record does not describe how missing endpoint measurements, incomplete follow-up, or unevaluable participants were handled. For survival outcomes, the censoring rules and completeness of follow-up are not reported. No assumptions about missingness or sensitivity analyses are described.
The primary endpoint description identifies 36 patients as belonging to the phase I portion, while total enrollment is 50. The registry record does not state the analysis population for the secondary outcomes or give endpoint-specific denominators. It also does not report whether all enrolled participants were included in each analysis, or how exclusions were handled. Consequently, the stated enrollment cannot be assumed to be the denominator for every result.
There is no report of interim analyses or stopping rules in the registry record. The absence of these details should not be read as evidence that such procedures were or were not used; their status is not 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 and Fludarabine | 1 | 49 | 2.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Busulfan and Fludarabine | 45 of 49 |
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 and Fludarabine | 1 of 49 |
Most frequent serious adverse event terms
| Event term | Organ system | Busulfan and Fludarabine |
|---|---|---|
| Sepsis | Blood and lymphatic system disorders | 1 of 49 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Busulfan and Fludarabine |
|---|---|---|
| Mental Status change | Nervous system disorders | 1 of 49 |
Serious events with the highest arm-level rate: sepsis (2.0%).
The registry record reports one study group titled Busulfan and Fludarabine. For serious adverse events, it lists 49 participants at risk and 1 affected. For other adverse events, it also lists 49 at risk and 1 affected. These counts describe the entries as recorded; the record does not provide an observation period or explain whether a participant could contribute to more than one event category.
Sepsis is listed among the top serious terms at 2.0%. The record does not clarify the precise denominator or time window associated with this percentage, so it should not be used to infer a rate beyond what is expressly listed. The overall death count is 45, but the record does not report cause, timing, attribution, or follow-up context. It cannot be interpreted as an estimate of treatment-related mortality or as a survival result.
General statistical explanation: Adverse-event counts are easiest to interpret when the denominator, surveillance period, event definitions, severity criteria, and handling of repeated events are clear. A count of affected participants is different from a count of event episodes, and neither alone establishes whether an event was caused by treatment. The registry record does not report all of these details, so the safety figures are descriptive and have limited interpretive context.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase I-II, single-group study with enrollment of 50. It identifies a regimen involving busulfan and fludarabine conditioning for transplantation with in-vivo T-cell depletion, and names maximum tolerated dose as the primary endpoint. It also lists overall survival and disease-free survival as secondary outcomes. These details establish what the study set out to investigate, but not the numerical findings.
The primary maximum tolerated dose value is not reported in the registry record. Neither are the survival estimates, their precision, or the outcome definitions needed to interpret them. The registry therefore does not permit a quantitative judgment about the magnitude or uncertainty of those outcomes. A completed status does not fill that reporting gap.
The design is single-group, with no comparator. The posted information cannot show how outcomes under the regimen differ from outcomes under another treatment. Nor does the record provide the data needed to assess causal effects, such as a randomized contrast. The safety counts and death count are descriptive entries and do not resolve that limitation.
General interpretation: Early-phase dose-finding and single-group clinical research can contribute information about treatment exposure, observed tolerability, and outcomes within the enrolled group. Their conclusions depend on protocol rules, outcome ascertainment, and sufficient reporting. In this case, those methodological details and the central numerical result are not reported in the registry record. The appropriate reading is therefore limited to the design, stated aims, and listed descriptive counts, rather than a conclusion about comparative effects.
13. Why This Trial Matters Statistically
This study is statistically notable for combining a dose-finding question with longer-term outcomes in a phase I-II program. The primary endpoint is framed as a maximum tolerated busulfan AUC, while overall survival and disease-free survival are also named. These outcomes require different methods and different supporting information: exposure and toxicity rules for the dose-finding endpoint, and event definitions and follow-up for survival.
The single-group design is central to interpreting the evidence. It can describe outcomes among participants treated with the regimen, but it does not provide a concurrent estimate of how outcomes compare with an alternative. Recognizing this distinction helps prevent descriptive counts from being read as comparative effects.
The record also illustrates why endpoint reporting needs precision. The primary endpoint has two different unit expressions in its description, and its result is not reported. The phase I endpoint population is identified as 36 patients, while total enrollment is 50; the analysis populations for other outcomes are not stated. These details affect whether the endpoint and denominator can be understood consistently.
Finally, the named survival aims and reported adverse-event entries do not replace complete statistical reporting. Estimates, uncertainty, follow-up, event definitions, and analysis populations are necessary to assess what the data show and how precisely they do so. The registry record is informative about the study’s structure and intent, but it does not include those elements for the principal clinical outcomes.
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 registry record restrict interpretation. First, the numerical maximum tolerated dose result is absent, despite being identified as the primary endpoint. The listed endpoint unit is mmol-min/L, whereas the description gives µmol-min/L; the record does not reconcile this difference.
Second, the study is single-group and has no listed comparator. Outcomes within the treated group therefore do not provide a direct comparison with an alternative regimen. Third, the record names overall survival and disease-free survival but does not report their estimates, definitions, event counts, follow-up, or uncertainty.
The primary endpoint population is described as 36 patients in the phase I portion, while overall enrollment is 50. The record does not explain the analysis populations for other endpoints or provide endpoint-specific denominators. It also does not report the dose-finding rules, toxicity definitions, missing-data methods, censoring approach, or analysis plan. These omissions make it difficult to reconstruct how outcomes were defined and analyzed.
The adverse-event information gives limited context: it lacks a reported observation period and does not specify event attribution or how repeated events are handled. The death count has no accompanying timing or cause information. These registry limitations do not establish that details were absent from study documents; they mean only that the relevant information is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies — NCT00943319.
- Registry record last updated 2019-02-04; status last verified 2019-02.
- Results first posted 2019-02-04.
- 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 record describes NCT00943319, a phase I-II, completed, single-group study sponsored by the University of Chicago. It lists enrollment of 50, no masking, and study dates of 2012-03 to 2017-12. The study concerns busulfan-fludarabine conditioning and T-cell-depleted allogeneic stem cell transplantation for advanced hematologic malignancies.
Maximum tolerated dose is the primary endpoint, described as a busulfan AUC measure; the endpoint population is identified as 36 patients in the phase I portion. Overall survival and disease-free survival are listed as secondary outcomes. The maximum tolerated dose value and survival estimates are not reported in the registry record. The endpoint unit is inconsistent between the listing and description.
The record lists 49 participants at risk and 1 affected for both serious and other adverse events, Sepsis at 2.0% among the top serious terms, and 45 deaths. Timing, attribution, follow-up context, and endpoint analysis details are not reported in the registry record.