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/Clofarabine + Allogeneic Stem Cell Transplantation (NCT01643668), a na phase 2 study. The primary outcome is Assessment of Donor Stem Cell Engraftment: ANC Count.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01643668 |
| Phase | Phase 2 |
| Condition | Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome undergoing allogeneic stem cell transplantation. The registry describes transplantation using stem cells from a matched related donor or a matched unrelated volunteer donor. The primary engraftment assessment excluded one participant who experienced early death before engraftment; the measure was assessed among the remaining 33 evaluable participants.
Intervention
The treatment approach was reduced intensity conditioning with busulfan and clofarabine, followed by allogeneic stem cell transplantation. The registry describes chemotherapy intended to suppress the recipient’s immune system before infusion of donor stem cells. The stated rationale was to use clofarabine’s activity in these diseases to increase the anti-tumor effects of conditioning without unacceptable toxicity. That rationale is not itself evidence of an outcome.
Comparator
There was no separate control group. The study is identified as single group, with all participants treated in an identical manner. Allocation is listed as not applicable and masking as none. Its posted results therefore do not provide a randomized, like-for-like comparison against another conditioning regimen or against no treatment.
Primary question
The primary outcome asked whether donor stem cell engraftment occurred after transplantation. Engraftment required an absolute neutrophil count of at least 500 cells/uL for 3 consecutive measurements and at least 75% donor-derived hematopoietic elements by peripheral blood chimerism assays before day +40. The registry lists assessment at 1, 2, 3, and 4 weeks after transplantation. Although the endpoint definition and evaluable population are reported, the number who met the definition is not reported in the registry record. The primary outcome result therefore cannot be described from this record.
3. Trial Design
This was a phase II study of reduced intensity conditioning with busulfan and clofarabine followed by allogeneic stem cell transplantation. The registry identifies the study model as single group and lists 34 enrolled participants. The study status is completed. The recorded start was 2012-07, and primary completion was 2016-08.
There was no randomized allocation: allocation is listed as not applicable. Masking is listed as none. The arm description identifies one treatment approach, busulfan and clofarabine reduced intensity conditioning followed by allogeneic transplantation. The registry’s brief description says participants were treated in an identical manner. Consequently, the design can describe outcomes in the treated group, but it cannot isolate a treatment effect by comparing that group with a concurrent control.
The record describes the clinical rationale as addressing relapse risk after reduced intensity transplantation, while seeking anti-tumor activity from clofarabine without unacceptable toxicity. This is the stated motivation, not a finding from the study. The primary outcome was donor cell engraftment; listed secondary outcomes included non-relapse mortality, progression-free and overall survival, graft-versus-host disease, hepatic veno-occlusive disease, severe toxicities, and infection-related complications.
The registry record does not report the protocol’s statistical analysis plan, sample-size justification, interim analyses, or details of any outcome-analysis methods. Enrollment is a design characteristic and should not be confused with the population assessed for the primary endpoint: one participant experienced early death before engraftment, and 33 evaluable participants were assessed.
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 | BuClo RIC + SCT |
|---|---|
| STARTED | 34 |
| COMPLETED | 33 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | BuClo RIC + SCT |
|---|---|
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: One participant experienced early death before engraftment. Outcome measure was assessed among the remaining 33 evaluable participants.
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 | BuClo RIC + SCT |
|---|---|---|
| Participants analysed | 34 | |
| Age, Continuous | years | 63.5 (25 to 74) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 25 |
| Region of Enrollment: United States | Participants | 34 |
| Diagnosis: Acute Myeloid Leukemia (AML) | Participants | 25 |
| Diagnosis: Myelodysplastic Syndrome (MDS) | Participants | 5 |
| Diagnosis: Acute Lymphoblastic Leukemia (ALL) | Participants | 4 |
| Hematopoietic Cell Transplantation (HCT) Refined Disease Risk Index (DRI): Low | Participants | 1 |
| Hematopoietic Cell Transplantation (HCT) Refined Disease Risk Index (DRI): Intermediate | Participants | 27 |
| Hematopoietic Cell Transplantation (HCT) Refined Disease Risk Index (DRI): High | Participants | 6 |
| Disease Stage: First Complete Remission (CR1) | Participants | 25 |
| Disease Stage: Second Complete Remission (CR2) | Participants | 6 |
| Disease Stage: Partial remission/active disease/blasts >5% | Participants | 3 |
| Cytogenics for patients with AML/MDS: Favorable | Participants | 1 |
| Cytogenics for patients with AML/MDS: Intermediate | Participants | 24 |
| Cytogenics for patients with AML/MDS: Adverse | Participants | 5 |
| ALL Cytogenics: Philadelphia Chromosome | Participants | 2 |
| ALL Cytogenics: Other | Participants | 2 |
| Hematopoietic cell transplantation specific comorbidity index (HCT-CI) | units on a scale | 1 (0 to 9) |
| Donor Type: Matched Related | Participants | 11 |
| Donor Type: Matched Unrelated | Participants | 23 |
| Cytomegalovirus Serostatus: Either donor or host positive for virus | Participants | 22 |
| Cytomegalovirus Serostatus: Both negative for virus | Participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Assessment of Donor Stem Cell Engraftment: ANC Count, measured over 1, 2, 3, and 4 weeks after transplantation.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was donor stem cell engraftment, assessed using blood count and donor-origin criteria. A participant met the registry’s definition if the absolute neutrophil count reached at least 500 cells/uL for 3 consecutive measurements and at least 75% of hematopoietic elements were donor-derived, as determined by peripheral blood chimerism assays before day +40 after transplantation. The listed assessment time points were 1, 2, 3, and 4 weeks after transplantation.
This combines evidence of blood-cell recovery with evidence that the recovered hematopoietic elements came predominantly from the donor. In general, an operational endpoint definition makes clear what counts as an event, supporting consistent classification across participants. The registry describes the threshold and timing but does not report how many participants met the definition. One participant experienced early death before engraftment; the outcome was assessed among the remaining 33 evaluable participants.
Engraftment is an early transplant outcome, but it is not interchangeable with longer-term outcomes such as survival, relapse, or graft-versus-host disease. Those are listed separately as secondary outcomes. The endpoint definition alone cannot establish the observed engraftment frequency or how the regimen compares with another approach.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study design, endpoint definition, and primary-outcome assessment population, but does not report the primary endpoint result. It is therefore not possible to state how many evaluable participants achieved donor stem cell engraftment, or to describe the precision of an estimated engraftment frequency. The record’s stated enrollment of 34 and the 33 evaluable participants are not a substitute for the missing outcome count.
The endpoint required both neutrophil recovery and evidence of donor-derived hematopoietic elements within the specified period. A participant meeting only one part of that definition would not meet the stated endpoint. The record reports the criteria but does not provide the component-level results, timing of engraftment, or an uncertainty interval for the outcome.
The study has a single treatment group and no randomized control arm. Its results, if reported, could describe outcomes among participants treated with busulfan and clofarabine conditioning followed by allogeneic transplantation. They could not by themselves distinguish the regimen’s effect from other explanations, including the natural course of disease, participant characteristics, donor characteristics, supportive care, or other aspects of transplant care. A comparison with another regimen would require appropriate comparative data, which this record does not provide.
The registry lists secondary outcomes covering survival, non-relapse mortality, graft-versus-host disease, hepatic veno-occlusive disease, toxicities, and infections. Their presence in the outcome list does not establish that results are reported. No secondary outcome estimates or analyses are included in the record’s posted results information summarized by these registry entries. The record lists nine outcome measures and zero analyses.
Safety information should also be read descriptively. The registry reports affected-participant counts for serious and other adverse events, a death count, and selected serious adverse-event terms with percentages. These figures do not establish that an event was caused by the conditioning regimen or transplantation. With no concurrent control group and no described causal analysis, the figures cannot quantify excess risk attributable to treatment.
In short, the posted information supports a description of the trial’s question and design, but not an estimate of the primary outcome or a comparative conclusion about effectiveness or safety. Missing outcome results should be treated as missing from the registry record, rather than interpreted as evidence that an outcome did or did not occur.
9. Statistical Methods Explained
The design determines what statistical conclusions are possible. This is a single-group phase II study with no masking and no randomized allocation. A single-group analysis can describe the outcomes observed in the treated participants. It does not create a direct estimate of the difference between treatment approaches, because no concurrent comparison group is reported. In general, an observed outcome in one group can reflect both the treatment and other characteristics of the people and care involved.
What does a binary endpoint represent?
The primary endpoint is a participant-level event: meeting the specified engraftment criteria or not meeting them. For a binary outcome, a basic descriptive summary would state the number meeting the definition and the number assessed. An estimated event proportion can then be accompanied by a confidence interval. In general, a confidence interval describes the uncertainty associated with an estimate under the statistical method used; it is not a guarantee that the true value lies within a particular interval. The registry record gives the assessment population but does not report the number meeting the endpoint, an estimated proportion, or a confidence interval.
The outcome’s definition combines two conditions: an absolute neutrophil count of at least 500 cells/uL for 3 consecutive measurements, and at least 75% donor-derived hematopoietic elements by chimerism assessment before day +40. Those criteria are part of the endpoint, not separate treatment comparisons. The time frame lists assessments at 1, 2, 3, and 4 weeks after transplantation. The record does not state how an outcome measured at different visits was handled in the statistical analysis, or whether any additional rules were applied.
How should the analysis population be understood?
The registry says one participant experienced early death before engraftment and that the endpoint was assessed among the remaining 33 evaluable participants. This identifies the population used for that outcome assessment. It does not explain the protocol’s analysis-population definitions or describe how the early death was handled analytically beyond the reported evaluable population. In general, excluding participants from an endpoint denominator can affect interpretation, particularly if the reason for exclusion is related to the outcome. The record does not provide enough information to assess the implications of this exclusion or to reconstruct an alternative analysis.
Enrollment and endpoint assessment are different concepts. The record lists 34 enrolled participants, while the primary endpoint assessment population is reported as 33 evaluable participants. These figures should not be turned into an outcome rate without the number who achieved engraftment. Nor should an assumed outcome be assigned to the participant who experienced early death: the registry’s stated assessment population does not report such a classification.
What can the secondary outcomes contribute?
The registry lists non-relapse mortality, progression-free and overall survival, acute and chronic graft-versus-host disease, hepatic veno-occlusive disease, grade 3 or 4 toxicities, and infection-related complications among secondary outcomes. Some of these are time-to-event outcomes, and some concern the occurrence or severity of events. In general, time-to-event methods account for the time until an event and may account for participants whose event status is not known through the full follow-up period. Cumulative-incidence methods can be relevant when different event types prevent one another from occurring first. These are general statistical considerations, not descriptions of methods used in this study. The registry record does not report the analytical methods for these outcomes or their estimates.
For adverse events, counts and percentages are descriptive summaries. Their interpretation depends on the definitions, observation periods, and denominator used. The record lists participants at risk and affected counts for serious and other adverse events, plus selected serious-event terms with percentages. It does not describe a comparative safety analysis or establish causal attribution. A list of event terms does not indicate whether events were new, recurrent, related to treatment, or concentrated in particular participants unless the registry supplies those details.
What do planning illustrations mean?
Any sample-size figures associated with this record are planning illustrations, not observed power and not the trial’s reported design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Time-to-event illustrations use the total number of events; other illustrations use participants per arm. These assumptions describe hypothetical planning calculations and do not change the actual single-group design. The registry record does not report the trial’s own sample-size justification. An illustration based on an observed effect should not be read as proof that the study had a particular probability of detecting an effect, nor as evidence of a treatment effect.
The record lists zero analyses. It does not report a statistical analysis plan, hypothesis tests, confidence intervals, adjustment for multiple outcomes, or interim analyses. In general, such details help readers understand which analyses were planned, how uncertainty was quantified, and how the chance of false-positive findings across multiple tests was managed. Without those details and without reported endpoint estimates, no inferential result can be reconstructed from the design description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including the primary engraftment outcome and secondary outcomes related to non-relapse mortality, survival, graft-versus-host disease, hepatic veno-occlusive disease, severe toxicities, and infection-related complications. Evaluating multiple outcomes can raise a multiplicity issue: in general, the more hypotheses tested, the greater the opportunity for at least one result to appear noteworthy by chance. Statistical plans sometimes address this through a prespecified hierarchy or adjustment, but the registry record does not report whether any such approach was planned or used.
The record lists zero analyses. It does not report p-values, confidence intervals, a statistical analysis plan, or an interim-analysis plan. No conclusion about multiplicity adjustment can therefore be drawn. The outcome list identifies what was intended for assessment, not which outcomes were analyzed or whether selective reporting occurred.
For the primary outcome, one participant experienced early death before engraftment and the assessment population is reported as 33 evaluable participants. The record does not describe missing-data rules, whether other assessments were unavailable, or how incomplete observations were handled. In general, the consequences of missing data depend on why information is missing and how the analysis treats it. Those details are not reported in the registry record, so no assumption about the missingness mechanism or its effect on the endpoint estimate is justified.
The record’s identification of an evaluable population should be kept distinct from an intention-to-treat analysis or another prespecified analysis population. The registry does not report such population definitions. It also does not report whether all secondary outcomes were available for all participants. These gaps limit assessment of the completeness and multiplicity of the outcome analyses.
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 |
|---|---|---|---|
| Treatment Arm | 14 | 34 | 41.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Arm | 15 of 34 |
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 |
|---|---|
| Treatment Arm | 24 of 34 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Arm |
|---|---|---|
| Neutrophil Count Decreased | Investigations | 3 of 34 |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | 2 of 34 |
| Acute Kidney Injury | Renal and urinary disorders | 1 of 34 |
| Alanine aminotransferase increased | Investigations | 1 of 34 |
| Anemia | Blood and lymphatic system disorders | 1 of 34 |
| Blood bilirubin increased | Investigations | 1 of 34 |
| Erythroderma | Skin and subcutaneous tissue disorders | 1 of 34 |
| Hypertension | Vascular disorders | 1 of 34 |
| Hypertriglyceridemia | Metabolism and nutrition disorders | 1 of 34 |
| Lung Infection | Infections and infestations | 1 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Arm |
|---|---|---|
| Neutrophil count decreased | Investigations | 5 of 34 |
| Anemia | Blood and lymphatic system disorders | 4 of 34 |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | 4 of 34 |
| Platelet count decreased | Investigations | 4 of 34 |
| Blood bilirubin increased | Investigations | 3 of 34 |
| Hypertension | Vascular disorders | 3 of 34 |
| Lung infection | Infections and infestations | 3 of 34 |
| Nausea | Gastrointestinal disorders | 3 of 34 |
| Anorexia | Metabolism and nutrition disorders | 2 of 34 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 34 |
Serious events with the highest arm-level rate: neutrophil count decreased (8.8%), respiratory failure (5.9%), acute kidney injury (2.9%), alanine aminotransferase increased (2.9%), anemia (2.9%).
The registry reports 34 participants at risk for the treatment arm, 14 affected by serious adverse events, 24 affected by other adverse events, and 15 deaths. These are separate registry fields and should not be added together: participants may be represented in more than one category, and the record does not explain overlap or provide an event-level breakdown. The death count is not, by itself, a count of deaths caused by treatment.
The listed serious adverse-event terms include Neutrophil Count Decreased at 8.8%, Respiratory Failure at 5.9%, Acute Kidney Injury at 2.9%, Alanine aminotransferase increased at 2.9%, Anemia at 2.9%, and Blood bilirubin increased at 2.9%. These percentages are reported as registry values; their denominator and any event-level counting rules are not described in the record. The terms identify reported serious events, not proof that the regimen caused them.
In general, safety counts are descriptive unless a suitable comparison and analysis support a causal interpretation. This study has no concurrent control group. The registry does not report event timing, treatment relatedness, recurrence, or a comparative safety estimate. The figures therefore describe reported safety information but do not quantify the additional risk attributable to the regimen.
12. What the Result Does, and Does Not, Mean
The record describes a phase II investigation of busulfan and clofarabine reduced intensity conditioning followed by allogeneic stem cell transplantation. Its primary question concerned donor stem cell engraftment, defined using neutrophil recovery and donor-derived hematopoietic elements within a specified period. The record also documents that one participant experienced early death before engraftment and that the endpoint was assessed among 33 evaluable participants.
The primary endpoint result itself is not reported in the registry record. There is no stated number of participants meeting the definition, no event proportion, and no uncertainty interval. As a result, the record does not establish the observed frequency of engraftment. The enrollment count cannot fill that gap, because it does not indicate how many participants met the primary endpoint.
The single-group design also limits what any reported outcome could mean. Without a randomized or other concurrent control group, a descriptive outcome cannot show how the same population would have fared under a different conditioning strategy. Nor can the rationale for adding clofarabine be treated as a measured result. The stated rationale explains why the study was undertaken; it is not evidence of benefit or of acceptable toxicity.
The adverse-event and death figures provide descriptive safety information, but the registry does not establish treatment attribution or provide a control-group comparison. Similarly, listing survival, relapse-related, graft-versus-host disease, and other secondary outcomes does not mean those outcomes have reported results in this record.
In general, clinical interpretation depends on both the observed estimates and their uncertainty, the design, and the completeness of follow-up and analysis. Here, key outcome estimates and analytical details are not reported in the registry record. The defensible reading is therefore limited to what the study set out to measure, how the endpoint was defined, who was included in its assessment, and the descriptive safety entries. No claim that the regimen works or does not work follows from these registry entries.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined endpoint and a reported endpoint result are both necessary. The registry gives a detailed operational definition of engraftment, including a neutrophil threshold, a requirement for consecutive measurements, donor-origin evidence, and a time limit. That definition tells readers what would count as success for the primary outcome. Without the number of participants who met it, however, the central result cannot be estimated or interpreted.
The distinction between enrollment and the outcome assessment population is also important. The registry lists 34 enrolled participants, while the primary outcome was assessed among 33 evaluable participants after one participant experienced early death before engraftment. Statistical interpretation depends on knowing who was included in an analysis and how outcomes were classified. The record supplies part of that information, but does not report the outcome count or the broader analysis-population rules.
The single-group design highlights the difference between describing an outcome and estimating a comparative treatment effect. A one-arm phase II study can characterize outcomes in its participants, but a separate comparator is needed for a direct contrast between regimens. This distinction matters especially when the study’s rationale concerns reducing relapse while avoiding unacceptable toxicity: those competing aims need outcome evidence and an appropriate basis for comparison.
Finally, the registry’s safety entries show why event counts require context. Counts, listed percentages, attribution, overlap, and observation time answer different questions. Without a concurrent comparison or further analytical detail, descriptive safety data should not be interpreted as a causal estimate. The record is useful for understanding the study’s intended question and measurement framework, while its missing results constrain the statistical conclusions available to readers.
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 main limitation for interpreting the primary question is that the registry record does not report the number of participants who achieved engraftment. It provides the endpoint criteria and identifies 33 evaluable participants, but without the event count there is no estimable primary-outcome frequency in the record. No confidence interval or other measure of precision is reported.
The study is single group, with no randomized allocation or concurrent comparator. This prevents a direct comparison with another conditioning strategy and limits causal conclusions. Masking is listed as none. The record does not report the statistical analysis plan, the sample-size justification, interim analyses, or methods used for the listed secondary outcomes.
The early death before engraftment is reported, but the record does not describe how this event was treated analytically beyond stating that the outcome was assessed among the remaining evaluable participants. It does not report other missing-data rules, follow-up completeness, or analysis populations for secondary outcomes. These omissions make it difficult to assess the effect of exclusions or incomplete observations.
The safety information is also limited for comparative interpretation. The record lists affected counts and selected serious adverse-event terms, but does not report event timing, treatment relatedness, recurrence, or overlap among categories. Because there is no control group, these entries do not establish which events were caused by the regimen. The listed secondary outcomes do not have reported results in the registry record, and the record identifies zero analyses. These limitations concern the available registry information and do not establish what may or may not have been reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation — NCT01643668.
- Registry record last updated 2017-07-13; status last verified 2017-06.
- Results first posted 2017-07-13.
- 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
This completed phase II study evaluated busulfan and clofarabine reduced intensity conditioning followed by allogeneic stem cell transplantation in a single group. The record lists 34 enrolled participants and no randomized allocation or masking. Its primary outcome was donor stem cell engraftment, defined using neutrophil recovery and donor-derived hematopoietic elements within the stated time frame. One participant experienced early death before engraftment; the outcome was assessed among 33 evaluable participants.
The primary outcome count and its uncertainty are not reported in the registry record. Secondary outcomes are listed, but their results and analysis methods are not reported in the information available in the record. Adverse-event counts and selected serious-event terms are reported descriptively; they do not establish treatment causality or comparative risk. The single-group design supports description, not a randomized comparison.