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 Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Allo-HSCT in Hematological Malignancies (NCT00544466), a na phase 1, phase 2 study. The primary outcome is Number of Grade 3 and Above Toxicities of Helical Tomotherapy (HT) in Combination With Fludarabine and Melphalan Followed by Allogeneic Stem Cell Transplantation..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00544466 |
| Phase | Phase 1, Phase 2 |
| Condition | Leukemia, Myelodysplastic Syndromes |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 75 |
| Arms in the primary outcome | n/a |
| Lead sponsor | City of Hope Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with hematologic malignancies, with leukemia and myelodysplastic syndromes listed as conditions. The registry records enrollment of 75.
Intervention
A preparative regimen of helical tomotherapy, fludarabine phosphate, and melphalan followed by allogeneic hematopoietic stem cell transplantation.
Comparator
There is no separate comparison group in the registry design. The study is listed as single-group, with allocation recorded as not applicable and masking as none.
Primary question
What number of grade 3 and above toxicities was observed following the regimen and transplant, within the primary outcome timeframe of 100 days post treatment?
This clinical question is primarily about toxicity in the context of a combined treatment strategy. The primary outcome names the number of events, rather than a comparison between treatments or a direct measure of treatment benefit. The registry says toxicities were evaluated using the modified Bearman Scale and the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The primary outcome result itself is not reported in the registry record, so the recorded outcome definition does not establish how many events occurred.
The registry also lists overall survival on Day 180 post-transplant as a secondary outcome. It does not report that outcome’s result in the registry record for interpretation. Because there is no control group, the study’s structure does not support a direct estimate of how this regimen compares with another treatment. Its focus is the regimen and transplant in the enrolled population, not a randomized treatment contrast.
3. Trial Design
The registry describes a phase 1 and phase 2 study with a single-group model. Allocation is recorded as not applicable, and masking is listed as none. The registry records enrollment of 75 and identifies City of Hope Medical Center as the sponsor. The study start date is 2006-07-31, the primary completion date is 2013-08-01, and the status is active, not recruiting.
The treatment sequence begins with a preparative regimen. Patients receive fludarabine phosphate intravenously on days -7 to -3 and melphalan intravenously on day -2. They also undergo helical tomotherapy twice daily on days -7 to -4. Allogeneic hematopoietic stem cell transplantation is scheduled on day 0. The registry lists intensity-modulated radiation therapy as an intervention as well as the named drugs and transplant procedure.
With a single group, the observations describe people receiving the regimen; they do not compare outcomes against a concurrently assigned control group. General statistical interpretation: without a like-for-like control, differences from other settings cannot be attributed to this regimen using this study alone. The registry explicitly identifies the study as not being a randomized comparison. No alternative regimen, usual-care group, or untreated group is listed as a comparator.
The registry lists a primary toxicity outcome and overall survival on Day 180 post-transplant as a secondary outcome. It records two outcome measures, but the second outcome measure’s details are not reported in the registry record. No statistical analyses are listed. The record does not report a sample-size justification, a detailed statistical plan, or whether interim analyses were planned or conducted. The status of active, not recruiting does not, by itself, supply missing outcome results or analysis details.
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 | Treatment (Enzyme Inhibitor, Radiation Therapy, Transplant) |
|---|---|
| STARTED | 62 |
| COMPLETED | 62 |
| 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.
Population: Patients consented to the study.
| Characteristic | Unit | Treatment (Enzyme Inhibitor, Radiation Therapy, Transplant) |
|---|---|---|
| Participants analysed | 75 | |
| Age, Continuous | years | 55 (9 to 70) |
| Sex: Female, Male: Female | Participants | 40 |
| Sex: Female, Male: Male | Participants | 35 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 7 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 |
| Race (NIH/OMB): White | Participants | 62 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 75 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Grade 3 and Above Toxicities of Helical Tomotherapy (HT) in Combination With Fludarabine and Melphalan Followed by Allogeneic Stem Cell Transplantation., measured over 100 days post treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | events |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the number of grade 3 and above toxicities associated with helical tomotherapy in combination with fludarabine and melphalan followed by allogeneic stem cell transplantation. Its unit is events, and its timeframe is 100 days post treatment. The registry says toxicities were evaluated with the modified Bearman Scale and the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
In general, a toxicity endpoint captures harms observed during treatment or follow-up and can help describe the safety profile of a regimen. A count of events conveys how many qualifying events were recorded, but it is not automatically the same as the number of affected participants: an individual may contribute more than one event, depending on how outcomes are defined and recorded. The registry’s primary outcome description does not state whether the reported count is a count of events, people, or both beyond identifying the unit as events.
The primary outcome result is not reported in the registry record. Therefore, the outcome definition and assessment scales explain what was intended to be measured, but they do not establish the observed toxicity count or its precision. The record also does not report a confidence interval or an analysis of this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The most important interpretive feature is the mismatch between a defined primary outcome and the absence of its result in the registry record. The primary outcome is the number of grade 3 and above toxicities in the 100 days post treatment. No value for that outcome, uncertainty interval, or statistical analysis is reported. As a result, the record does not support a numerical estimate of the primary toxicity burden or an assessment of its precision.
The safety information does include a group with 62 at risk for serious adverse events and 13 affected, and 62 at risk for other adverse events and 61 affected. The record also lists 43 deaths. These are descriptive registry entries. They should not be substituted for the unreported primary endpoint: the categories and timeframes are not established as identical in the registry entries. The listed deaths cannot be attributed to the regimen based on these fields alone.
The serious adverse-event terms are accompanied by percentages, including infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) at 11.3%, hypoxia at 11.3%, supraventricular and nodal arrhythmia at 8.1%, hypotension at 6.5%, ALT, SGPT at 6.5%, and creatinine at 6.5%. These entries indicate which terms appear among the listed serious events and the percentages recorded for them. The available details do not specify the denominator used for each percentage or whether individual participants could contribute to more than one term. The percentages therefore should not be summed or treated as mutually exclusive portions of a whole.
The design also limits what can be inferred. A single-group study can describe outcomes among participants who received the regimen, but it does not provide a randomized comparison for estimating how outcomes would differ under another regimen. No adjusted treatment contrast, p-value, or confidence interval is reported. General statistical interpretation: estimates from a non-comparative study are descriptive of the observed group and can be affected by participant selection, follow-up, outcome recording, and clinical context.
The registry lists overall survival on Day 180 post-transplant as a secondary outcome, but its result is not reported in the registry record. Thus neither the primary toxicity result nor the listed secondary survival result can be interpreted quantitatively from the available outcome information. The safety entries remain relevant descriptive data, but they do not fill those outcome-reporting gaps.
9. Statistical Methods Explained
The registry identifies a phase 1 and phase 2, single-group study, with no masking and allocation recorded as not applicable. Those design details determine which statistical interpretations are possible. The record does not report a randomized comparison, so statistical explanations of treatment differences between arms do not apply to the trial’s observed design.
What can a single-group design estimate?
In general, a single-group study can describe outcomes observed in the group receiving the regimen. For a count outcome, a descriptive analysis might report the number of qualifying events and could also describe how events are distributed across participants, if those data are collected and reported. The primary outcome is specified in events, but the registry does not report its result or enough detail to know how the count was summarized. The record also does not report an uncertainty interval for that outcome.
A comparison with another treatment requires a credible reference group and a defined contrast. Here, the registry lists no separate control group. Outcomes from this study therefore cannot by themselves establish the difference that would have occurred under a different treatment. General statistical interpretation: a comparison to a historical or external group may be affected by differences in participants, care, follow-up, and outcome assessment; no such comparison is specified in the record.
What does an uncertainty interval convey?
General explanation: a confidence interval describes the range of values compatible with an estimate under a particular statistical model and its assumptions. It represents uncertainty in the estimate, not a guarantee that the true value lies inside a particular interval. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. No confidence interval for the primary outcome or the listed secondary outcome is reported in the registry record, so their statistical precision cannot be assessed from those outcomes.
How should event counts be read?
General explanation: a count of events and a count of people with at least one event answer different questions. Recurrent events in the same person can make the event count larger than the number of affected people. Conversely, a person-level indicator records whether a participant experienced an event, without counting repeated occurrences separately. The primary outcome is labeled as a number of events, while the safety fields separately report people at risk and affected. The registry does not describe whether repeated events were counted or how event timing and recurrence were handled.
For adverse-event terms, percentages are interpretable only with a clear denominator and definition of the percentage. The serious-event term list includes percentages, but its denominator is not reported in the registry entries. The terms may describe event types rather than disjoint categories; the record does not say whether a participant could appear under multiple terms. General statistical interpretation: when categories can overlap, adding their percentages does not produce a meaningful overall percentage.
What do the planning assumptions represent?
The posted planning illustrations use a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. Their stated effect is a fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events; for other illustrations, it is participants per arm. These are planning assumptions, not a description of the study’s single-group allocation and not the trial’s own design justification.
General explanation: planning calculations explore what sample size might be needed under chosen assumptions about the effect, variability, statistical threshold, and allocation. They do not measure the probability that this completed study found a real effect, and they are not observed power. The registry does not report its own sample-size justification. The posted assumption that an effect is based on an observed effect should not be confused with a reported result for the primary outcome, which is absent from the registry record.
What is not reported about the analysis?
The registry reports no analyses. It does not specify a statistical model for the primary event count, a method for handling repeated events, a confidence-interval procedure, or adjustments for other participant characteristics. Nor does it report whether any planned analysis was changed. These omissions mean that the analysis cannot be reconstructed from the outcome definition and safety listings alone.
General explanation: count data can be more variable than a simple model assumes, particularly when some participants experience multiple events while others experience few or none. Over-dispersion means that variability exceeds what a chosen count model expects; ignoring it can make uncertainty estimates too small. Whether over-dispersion is relevant depends on the data and model. The registry does not report the event-level data or a model that would allow this feature to be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary toxicity outcome, lists overall survival on Day 180 post-transplant as a secondary outcome, and records two outcome measures. Only one secondary outcome is described in the record. The second measure’s identity and details are not reported in the registry record. The results and analyses for the named outcomes are also not reported in the available record details.
Multiplicity concerns arise when a study examines several outcomes, time points, subgroups, or statistical tests. In general, the chance of at least one apparently unusual result can increase as more tests are considered. A prespecified hierarchy or an adjustment procedure may address this, but the registry record does not report a multiplicity strategy, testing hierarchy, or adjustment. The number of listed outcome measures alone does not establish how many analyses were conducted or how results were interpreted.
Missing-data methods and analysis populations are also not described. The registry does not report the number of participants with primary outcome data, the extent or reasons for missing observations, or how missing outcomes were handled. It does not identify an analysis population for the primary endpoint or explain whether participants were analyzed according to a particular follow-up or treatment-completion rule. These details matter because incomplete follow-up or unavailable assessments can affect a descriptive event count and its interpretation.
General statistical interpretation: missingness is not merely a smaller denominator; if the likelihood of missing data is related to outcomes or participant characteristics, the observed data may not represent all enrolled participants. The record does not provide enough information to assess that possibility. No interim analyses, stopping rules, or missing-data sensitivity analyses are reported.
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 (Enzyme Inhibitor, Radiation Therapy, Transplant) | 13 | 62 | 21.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Enzyme Inhibitor, Radiation Therapy, Transplant) | 43 of 62 |
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 (Enzyme Inhibitor, Radiation Therapy, Transplant) | 61 of 62 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor, Radiation Therapy, Transplant) |
|---|---|---|
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) | Infections and infestations | 7 of 62 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 7 of 62 |
| Supraventricular and nodal arrhythmia | Cardiac disorders | 5 of 62 |
| Hypotension | Cardiac disorders | 4 of 62 |
| ALT, SGPT (serum glutamic pyruvic transaminase) | Investigations | 4 of 62 |
| Creatinine | Investigations | 4 of 62 |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Investigations | 3 of 62 |
| Bilirubin (hyperbilirubinemia) | Investigations | 3 of 62 |
| Glucose, serum-high (hyperglycemia) | Investigations | 3 of 62 |
| Phosphate, serum-low (hypophosphatemia) | Investigations | 3 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor, Radiation Therapy, Transplant) |
|---|---|---|
| Nausea | Gastrointestinal disorders | 60 of 62 |
| Magnesium, serum-low (hypomagnesemia) | Investigations | 59 of 62 |
| Pain | General disorders | 58 of 62 |
| Albumin, serum-low (hypoalbuminemia) | Investigations | 58 of 62 |
| Sodium, serum-low (hyponatremia) | Investigations | 57 of 62 |
| Diarrhea | Gastrointestinal disorders | 56 of 62 |
| Calcium, serum-low (hypocalcemia) | Investigations | 56 of 62 |
| Potassium, serum-low (hypokalemia) | Investigations | 54 of 62 |
| Glucose, serum-high (hyperglycemia) | Investigations | 53 of 62 |
| Triglyceride, serum-high (hypertriglyceridemia) | Investigations | 51 of 62 |
Serious events with the highest arm-level rate: infection with grade 3 or 4 neutrophils (anc <1.0 x 10e9/l) (11.3%), hypoxia (11.3%), supraventricular and nodal arrhythmia (8.1%), hypotension (6.5%), alt, sgpt (serum glutamic pyruvic transaminase) (6.5%).
The registry’s safety entries list 62 at risk and 13 affected for serious adverse events, and 62 at risk and 61 affected for other adverse events. It also lists 43 deaths. These values describe the recorded safety fields; the record does not establish that the fields share the primary endpoint’s timeframe or definition. The listed deaths should not be read as evidence that treatment caused those deaths.
The serious adverse-event terms include infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) at 11.3%, hypoxia at 11.3%, supraventricular and nodal arrhythmia at 8.1%, hypotension at 6.5%, ALT, SGPT at 6.5%, and creatinine at 6.5%. The registry does not state the denominator for these percentages in the details. The terms may overlap, and the record does not explain whether a participant could contribute to more than one term. Therefore, the percentages are best read as separate reported entries, not as parts to add into a total.
The safety listings are not the same as the primary outcome result. The primary endpoint concerns grade 3 and above toxicities in the 100 days post treatment, and its result is not reported in the registry record. Nor do the safety entries alone establish a comparison with another treatment or a causal explanation for an event.
12. What the Result Does, and Does Not, Mean
The registry record establishes what the study set out to evaluate: a combined preparative regimen of helical tomotherapy, fludarabine phosphate, and melphalan followed by allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies. It specifies a primary toxicity outcome, the assessment scales, and the timeframe of 100 days post treatment. It also lists overall survival on Day 180 post-transplant as a secondary outcome.
It does not report the primary endpoint result or the secondary survival result in the available record details. Without those results, the number of primary toxicity events, the observed survival outcome, and the precision of either estimate cannot be described. The adverse-event entries offer separate descriptive safety information, but they do not substitute for the missing primary endpoint result or establish that events were caused by the regimen.
The single-group design has a further interpretive boundary. It can describe observed outcomes for people receiving the regimen, but there is no randomized comparator in the registry record. Consequently, the study does not estimate a treatment difference against another regimen and cannot separate the effects of the individual components from the combined treatment course. General statistical interpretation: an observed outcome in a single group does not reveal what would have happened to the same participants under an alternative treatment.
The registry’s enrollment and safety fields also do not resolve uncertainty about how many participants contributed primary endpoint data, how events were counted, or how missing observations were handled. No statistical analyses are reported. These gaps limit both quantitative interpretation and the assessment of bias or precision.
Accordingly, the record supports a description of the study’s design, treatment sequence, specified outcomes, and listed safety entries. It does not support a quantitative conclusion about the primary toxicity outcome, a comparative treatment effect, or a causal claim. Those distinctions are essential when reading a clinical trial registry entry whose outcome definitions are present but whose outcome results and analysis details are not.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and reporting need to be read together. The record names a primary toxicity outcome and defines its timeframe and assessment scales, but does not report its result. A precisely specified endpoint is useful for understanding what researchers intended to measure; it cannot answer how much toxicity was observed when the result itself is absent.
The single-group structure matters just as much. It provides no randomized comparator for a treatment contrast, so descriptive observations cannot be treated as evidence of what would happen relative to another regimen. This distinction is central to interpreting phase 1 and phase 2 studies, particularly when several treatment components are administered as one sequence.
The safety entries also show why denominators, outcome definitions, and overlapping categories matter. Counts of people at risk and affected, a count of events, percentages attached to serious-event terms, and deaths are different kinds of information. Without clear alignment of timeframe and denominator, one cannot treat them as interchangeable or combine them into a single summary.
Finally, the record illustrates the importance of analysis transparency. Statistical methods, missing-data handling, and analysis populations are not reported. General statistical interpretation: these details determine how estimates are formed and what uncertainty they carry. Their absence limits reproducibility and prevents a reader from assessing whether the analysis matched the outcome structure. The trial’s value for statistical interpretation therefore lies partly in recognizing what its registry record defines and what it leaves unresolved.
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 most direct limitation is that the registry record does not report the primary outcome result, despite specifying the number of grade 3 and above toxicities and the 100 days post treatment timeframe. It also does not report the result for overall survival on Day 180 post-transplant. The record lists two outcome measures, but the second measure is not identified in the available details.
The design is single-group, with no randomized comparison. That limits interpretation to description of outcomes in the treated group and prevents a direct estimate of a comparative treatment effect. The combined regimen also includes radiation, chemotherapy, and transplantation, so a single-group record cannot isolate the contribution of any component.
Additional outcome details are not reported: the primary event count, its uncertainty, the number of participants with evaluable outcome data, and how repeated events were handled. The safety listings do not specify the denominator for the percentages attached to serious-event terms, and the available details do not establish whether the listed categories overlap or share the primary endpoint timeframe.
The statistical plan, sample-size justification, analysis population, missing-data approach, multiplicity strategy, interim analyses, and sensitivity analyses are not reported in the registry record. These gaps constrain reproducibility and assessment of potential bias. The listed safety counts and deaths should also be interpreted descriptively; the record does not provide a basis for attributing them causally to the regimen. The status of active, not recruiting does not resolve these missing outcome or analysis details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Allo-HSCT in Hematological Malignancies — NCT00544466.
- Registry record last updated 2026-02-19; status last verified 2026-02.
- Results first posted 2023-05-10.
- 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 describes a phase 1 and phase 2, single-group study of helical tomotherapy, fludarabine phosphate, and melphalan followed by allogeneic hematopoietic stem cell transplantation for hematologic malignancies. The primary outcome is the number of grade 3 and above toxicities in the 100 days post treatment, evaluated using the modified Bearman Scale and NCI CTCAE version 3.0. Overall survival on Day 180 post-transplant is listed as a secondary outcome.
The registry records enrollment of 75, a study start date of 2006-07-31, a primary completion date of 2013-08-01, and status active, not recruiting. It includes descriptive adverse-event entries, but the primary and secondary outcome results, statistical analyses, missing-data methods, and analysis populations are not reported in the registry record. With no comparator group, the design does not provide a randomized estimate of a treatment difference.