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 Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia (NCT00453388), a non-randomized phase 2 study. The primary outcome is Number of Patients Who Engraft at Each Dose of TBI Used.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00453388 |
| Phase | Phase 2 |
| Condition | Acute Myeloid Leukemia in Remission, de Novo Myelodysplastic Syndrome, Fanconi Anemia |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Fred Hutchinson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns patients with Fanconi anemia receiving donor marrow transplantation. The registry describes groups based on history of hematologic malignancy and donor matching: HLA-haploidentical or HLA-matched unrelated donors. The recorded conditions also include acute myeloid leukemia in remission, de novo myelodysplastic syndrome, and previously treated myelodysplastic syndrome. Which conditions applied to each enrolled participant is not reported in the registry record.
Intervention
The treatment strategy combined fludarabine phosphate, cyclophosphamide, and total-body irradiation before allogeneic bone marrow transplantation, followed by mycophenolate mofetil and cyclosporine. The study varied the total-body irradiation dose in dose-escalation or dose-de-escalation groups. The registry describes the study as nonmyeloablative hematopoietic cell transplantation using alternative marrow donors.
Comparator
There was no randomized control group. The record describes four arms with different donor and disease-history categories and planned irradiation-dose strategies. Because the study was nonrandomized and the arms were not like-for-like control groups, comparisons between them cannot be interpreted as if treatment assignment had been randomized.
Primary question
The primary outcome was the number of patients who engrafted at each total-body irradiation dose, assessed up to Day 200. Engraftment was defined as greater than 95% donor chimerism. The registry record does not report the engraftment counts by dose, so it does not establish from the posted results how many patients met that definition or how the counts varied across dose levels.
3. Trial Design
This was a phase II, nonrandomized, parallel-group dose-finding study sponsored by Fred Hutchinson Cancer Center. The registry lists enrollment of 6 and a completed status. The recorded study dates are a start in 2007-02 and primary completion in 2013-06. The study was unmasked. A randomized allocation method is not reported; the record explicitly identifies allocation as nonrandomized.
The four arms were organized around donor type and history of hematologic malignancy. Arms I and III were dose-escalation groups for patients with a history of hematologic malignancy, respectively described with HLA-haploidentical and HLA-matched unrelated donors. Arms II and IV were dose-de-escalation groups for patients without such a history, with the same respective donor categories. The record states that no subjects meeting the criteria for Arms I or IV were enrolled. It does not give a complete account of which dose levels were received by each enrolled participant.
The intervention descriptions include fludarabine phosphate before transplantation, total-body irradiation before transplantation, and allogeneic bone marrow transplant, followed by cyclophosphamide, mycophenolate mofetil, and cyclosporine. The listed dose strategies include 2, 2.5, and 3 Gy for escalation, and 2, 2.5, 3, 1, and 0 Gy for de-escalation. Arm descriptions also specify treatment timing for some components, but the registry text is incomplete and does not support a full reconstruction of every arm’s regimen.
The registry lists transplant-related mortality and adverse events as secondary outcomes. It does not report the rationale for enrollment, the dose-escalation decision rules, or a statistical analysis plan. These details should not be inferred from the phase II or dose-finding labels.
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 | Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) |
|---|---|---|---|---|
| STARTED | 0 | 5 | 1 | 0 |
| COMPLETED | 0 | 5 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: No subjects meeting the criteria for Arms I or IV were enrolled.
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: No subjects meeting the criteria for Arms I or IV were enrolled.
| Characteristic | Unit | Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 0 | 5 | 1 | 0 | 6 | |
| Age, Categorical: <=18 years | Participants | — | 5 | 1 | — | 6 |
| Age, Categorical: Between 18 and 65 years | Participants | — | 0 | 0 | — | 0 |
| Age, Categorical: >=65 years | Participants | — | 0 | 0 | — | 0 |
| Age, Continuous | years | — | 11.1 (6.9 to 13.9) | 11.9 (11.9 to 11.9) | — | 11.1 (6.9 to 13.9) |
| Sex: Female, Male: Female | Participants | — | 5 | 0 | — | 5 |
| Sex: Female, Male: Male | Participants | — | 0 | 1 | — | 1 |
| Region of Enrollment: United States | participants | — | 3 | 1 | — | 4 |
| Region of Enrollment: Brazil | participants | — | 2 | 0 | — | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Who Engraft at Each Dose of TBI Used, measured over Up to Day 200.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients who engraft at each total-body irradiation dose, assessed up to Day 200. The registry defines engraftment as greater than 95% donor chimerism. Donor chimerism describes the contribution of donor-derived cells after transplantation; the endpoint therefore records whether a participant crossed the stated threshold rather than describing a continuous chimerism value.
Counts can be useful in an early dose-finding study because they show how often the specified biological outcome was observed within each dose group. They are also relatively direct to interpret: the endpoint is a participant count, not a modeled rate or a time-to-event estimate. However, counts alone do not show the precision of an estimated probability, and they need the corresponding number assessed at each dose to provide context. Those denominators and dose-specific engraftment results are not reported in the registry record.
The outcome is described as being followed up to Day 200. The record does not specify whether the endpoint was assessed at a single visit, how the threshold was measured, how missing assessments were handled, or whether any additional criteria were required. It also does not report the engraftment count results. Thus the endpoint definition is available, but its observed values and the uncertainty around them cannot be evaluated from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies engraftment as the primary outcome but does not provide the number of patients who engrafted at each dose. It also reports no statistical analyses for the outcome. Consequently, the posted record does not permit a direct estimate of the observed engraftment frequency by dose, a comparison between dose groups, or an assessment of uncertainty around such a comparison. The endpoint’s definition and follow-up period are stated, but those details are not substitutes for outcome counts.
Enrollment was 6, and the record says that no subjects meeting the criteria for Arms I or IV were enrolled. The adverse-event information lists participants at risk in Arm II and Arm III, but it does not give a dose-specific engraftment breakdown. The registry does not state how the enrolled participants were distributed across dose levels or whether everyone with an outcome assessment was included in the primary endpoint analysis. Those details are not reported in the registry record.
The design also constrains interpretation. Allocation was nonrandomized, and the arms differed in donor category and history of hematologic malignancy as well as in their planned dose strategies. Any comparison across arms could therefore reflect differences in the groups, treatment, or other factors; it would not be a like-for-like randomized comparison. The record itself cautions that the arms are not a like-for-like control comparison.
The safety figures are descriptive. In Arm II, 2 participants were recorded as affected by serious adverse events and 3 by other adverse events; 2 deaths are recorded. In Arm III, 0 participants were recorded as affected by either category and 0 deaths. The corresponding numbers at risk were 5 in Arm II and 1 in Arm III. These small group counts should be read as registry summaries, not as precise estimates of risk or evidence that observed events were caused by, or unrelated to, the intervention. The record does not report comparative safety analyses or attribution details.
Overall, the available record supports a description of the study’s question, design, endpoint definition, and selected safety counts. It does not support a conclusion about how often engraftment occurred at each dose or whether a particular dose strategy performed better. That absence of primary outcome results is a central limitation when interpreting the trial.
9. Statistical Methods Explained
The registry labels the trial nonrandomized and parallel. In a parallel study, participants are assigned to a group and the groups are followed as separate treatment pathways. In a randomized trial, assignment is determined by a chance process; here, allocation was not randomized. General statistical implication: without random allocation, baseline differences between groups can be entangled with treatment differences, making direct group comparisons harder to interpret. That concern is especially relevant because the arms are defined by donor type and history of hematologic malignancy as well as by irradiation-dose strategy.
What does a count endpoint tell us?
The primary outcome is a count of participants meeting the engraftment definition at each dose. A count is the number of observed participants with the specified outcome. To interpret it as a frequency, the number assessed in that dose group is also needed. A count without its denominator cannot establish the proportion of a group that experienced the outcome. The registry does not report the dose-specific engraftment counts or denominators, so neither a rate nor a comparison of rates can be read from the primary endpoint information.
General statistical explanation: an estimate based on a small group is usually less precise than an estimate based on a larger group, because each observed participant has more influence on the result. Confidence intervals express uncertainty around an estimate; a wider interval indicates less precision. The registry record does not report confidence intervals or other uncertainty estimates for engraftment. No interval can be reconstructed without the relevant outcome counts and denominators.
Why does the nonrandomized structure matter?
The four arms do not function as interchangeable control groups. They represent different combinations of donor category and disease-history criteria, with differing dose-escalation or dose-de-escalation plans. If outcomes differed across arms, the difference could not automatically be attributed to irradiation dose alone. General statistical explanation: confounding occurs when a characteristic related to both group membership and outcome makes an apparent treatment association difficult to separate from the effects of that characteristic. The record does not report an adjusted analysis intended to address such differences.
The listed dose strategies are part of the study description, but the registry does not report a complete dose-by-participant account or decision rules for moving between dose levels. It would therefore be inappropriate to assume which doses were actually administered, how dose choices were made, or what criteria governed escalation or de-escalation. Those protocol details are not reported in the registry record.
What can be concluded from the analysis information?
The record lists four outcome measures and two secondary outcome topics: transplant-related mortality and adverse events. It reports no outcome analyses. No effect estimate, test statistic, p-value, or confidence interval for the primary endpoint is reported in the registry record. Descriptive adverse-event counts are available, but these are not a substitute for an analysis comparing groups or estimating uncertainty.
General statistical explanation: a p-value, when reported, measures how compatible data are with a specified statistical model and null hypothesis; it is not a direct measure of clinical importance. A confidence interval communicates a range of values compatible with the data and model, subject to its assumptions. Neither type of inferential result is available for the primary endpoint in this record. The absence of these results means that statistical significance and precision cannot be assessed from the registry entry.
How should planning calculations be understood?
Any sample-size illustrations associated with the posted results are planning calculations, not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. For time-to-event outcomes, the stated quantity is a total event count; for other outcomes, it is participants per arm. These are general planning conventions rather than evidence that this study was designed with those assumptions. The record does not report the trial’s own sample-size justification, and no numerical planning results or observed primary effect are available in the registry record.
General statistical explanation: over-dispersion is variation greater than expected under a chosen statistical model. It can make standard errors too small if the model does not account for that extra variation. The primary outcome is recorded as a participant count, but the registry does not report a model for it, so there is no basis to claim that over-dispersion was assessed or to specify an adjustment. More broadly, conclusions from any model depend on its assumptions, analysis population, and handling of incomplete observations, none of which are detailed for the primary endpoint.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalati | 5 | 5 | 100.0% | 47.8% to 100.0% | 56.6% to 100.0% | 54.1% to 99.6% |
| Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 1 | 1 | 100.0% | 2.5% to 100.0% | 20.7% to 100.0% | 15.8% to 98.7% |
R code and output
arm <- c("Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalati", "Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation)")
n <- c(5, 1)
events <- c(5, 1)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalati 5 5 100.0 47.8 100.0 56.6 100.0 54.1 99.6
ARM Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) 1 1 100.0 2.5 100.0 20.7 100.0 15.8 98.711. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including the primary engraftment outcome and the secondary topics of transplant-related mortality and adverse events. It reports no outcome analyses. A plan for controlling multiplicity—the risk of finding an apparently notable result when several outcomes or comparisons are examined—is not reported in the registry record. The record also does not state which dose contrasts, if any, were intended as formal comparisons.
There is no reported primary endpoint analysis population beyond the statement that no subjects meeting the criteria for Arms I or IV were enrolled. The registry does not explain whether the primary analysis included all enrolled participants, only participants with an available engraftment assessment, or another defined population. It also does not report how participants with missing or unevaluable chimerism assessments were handled. These omissions matter because excluding participants with missing outcomes can change the interpretation of a count or frequency.
The registry does not report the amount or pattern of missing outcome data, any imputation method, or sensitivity analyses. It does not report interim analyses, stopping rules, or a prespecified statistical plan; these should not be inferred. General statistical explanation: multiplicity adjustments and missing-data methods depend on the planned questions and the way data are collected. Without those details and without the primary outcome results, readers cannot assess whether the reported record reflects a complete prespecified analysis or how robust any conclusion would be to alternative assumptions.
12. 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 |
|---|---|---|---|
| Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | 2 | 5 | 40.0% |
| Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 0 of 0 |
| Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | 2 of 5 |
| Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 0 of 1 |
| Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 0 of 0 |
| Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | 3 of 5 |
| Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | 0 of 1 |
| Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) |
|---|---|---|---|---|---|
| Death | Infections and infestations | 0 of 0 | 1 of 5 | 0 of 1 | 0 of 0 |
| severe abdominal pain associated with GVHD | Gastrointestinal disorders | 0 of 0 | 1 of 5 | 0 of 1 | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) | Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) | Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) |
|---|---|---|---|---|---|
| Mucositis | Gastrointestinal disorders | 0 of 0 | 2 of 5 | 0 of 1 | 0 of 0 |
| elevated bilitrubin | Hepatobiliary disorders | 0 of 0 | 2 of 5 | 0 of 1 | 0 of 0 |
| pulmonary hemorrage | Respiratory, thoracic and mediastinal disorders | 0 of 0 | 1 of 5 | 0 of 1 | 0 of 0 |
| acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 0 of 0 | 1 of 5 | 0 of 1 | 0 of 0 |
| diarrhea | Gastrointestinal disorders | 0 of 0 | 1 of 5 | 0 of 1 | 0 of 0 |
Serious events with the highest arm-level rate: death (20.0%), severe abdominal pain associated with gvhd (20.0%).
The registry reports serious adverse-event figures by arm, including the number at risk and the number affected. In Arm II, 5 participants were listed at risk for serious adverse events and 2 were affected; in Arm III, 1 was listed at risk and 0 were affected. For other adverse events, the corresponding figures were 5 at risk and 3 affected in Arm II, and 1 at risk and 0 affected in Arm III. The record lists 2 deaths in Arm II and 0 in Arm III. Arms I and IV have zero participants listed at risk.
The registry’s most frequent serious adverse-event terms are “Death” and “severe abdominal pain associated with GVHD,” each listed as 20.0%. These are registry-reported figures; the record does not explain the denominator or calculation behind the term percentages. The group counts are small, and zero affected participants in a group does not establish that an event is impossible or that the intervention caused no harm.
These numbers are descriptive, not a randomized safety comparison. The arms differ in eligibility and donor categories, and the registry does not report event attribution, timing, or a comparative analysis. The figures should therefore be read as the recorded counts, without attributing events to a particular treatment component or interpreting differences between arms as causal.
13. What the Result Does, and Does Not, Mean
The trial addresses a specific statistical question: how many patients meet a defined engraftment threshold at each total-body irradiation dose in a nonmyeloablative donor-transplant strategy for Fanconi anemia. The record provides the endpoint definition—greater than 95% donor chimerism—and the follow-up period of up to Day 200. It also describes dose-escalation and dose-de-escalation arms and reports enrollment of 6.
However, the registry does not report the primary engraftment counts by dose. Without those outcome values and denominators, the posted record cannot show the observed engraftment frequency, the variation across doses, or the precision of any estimate. It does not support a claim that one dose was better or worse, nor does it establish that the intervention did or did not achieve the endpoint.
The available safety information gives descriptive counts for serious and other adverse events and deaths in Arms II and III. Those figures provide a limited account of events recorded in the registry, but the record lacks a comparative safety analysis and does not describe event attribution. The reported counts cannot, by themselves, establish that the study treatment caused an event or that an absence of recorded events represents absence of risk.
The nonrandomized design and the differences between arm eligibility groups further limit comparisons. The arms were not like-for-like controls, and the record does not report adjusted analyses that could address group differences. The study’s phase II and dose-finding labels describe its stated design, but they do not supply missing outcome data or prove a particular dose-selection conclusion.
Thus, the meaningful conclusion from the registry entry is about what was studied and what was recorded, not about treatment efficacy. The endpoint and design are described, but the primary results needed to answer the central question are not reported in the registry record.
14. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and an outcome result are different kinds of information. The registry clearly defines engraftment using a donor-chimerism threshold and sets the observation period as up to Day 200. Yet it does not report the engraftment counts at the dose levels. Without the counts and the numbers assessed, readers cannot estimate the outcome frequency or judge its precision. A well-specified endpoint cannot replace the results needed to evaluate it.
The study also highlights the interpretive limits of dose-finding work that is nonrandomized. Dose groups may differ in characteristics that are also related to outcomes. In this trial, the arms are organized around donor type and history of hematologic malignancy, so a difference between arms cannot be isolated as a dose effect without additional design or analysis information. The record explicitly cautions that the arms are not like-for-like control comparisons.
Small group counts make descriptive safety figures particularly easy to overread. The serious and other adverse-event counts and the deaths provide information about what the registry records, but they do not offer precise comparative estimates. A zero count in a small group is not proof that risk is absent, and a difference in counts is not proof of causation.
Finally, the entry shows the importance of reporting analysis populations, missing-data handling, and uncertainty estimates alongside outcomes. Those details are not reported for the primary endpoint. Their absence limits the statistical conclusions that can be drawn, even though the study question, treatment components, and endpoint definition are described.
15. 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 limitation for interpreting this trial is that the registry record does not report the primary engraftment counts by dose. It also does not give the denominators assessed at each dose, uncertainty estimates, or a formal comparison. The primary outcome is therefore defined but not numerically interpretable from the posted results.
Enrollment is listed as 6, and the record states that no subjects meeting the criteria for Arms I or IV were enrolled. This leaves the stated four-arm structure incompletely represented in the enrolled population. The record does not describe the dose levels actually received by each participant, so the realized dose groups cannot be reconstructed from the arm labels alone.
Because allocation was nonrandomized, and the arms differ by donor type and history of hematologic malignancy, arm comparisons are vulnerable to differences beyond dose. No adjusted analysis is reported. The registry also does not report the dose-selection rules, the study’s own sample-size justification, or a complete statistical analysis plan.
Other important details are not reported in the registry record: the primary endpoint analysis population, missing or unevaluable outcome counts, missing-data methods, event attribution, and any interim analyses or stopping rules. The safety summaries are descriptive and do not establish causal relationships. These limitations restrict both efficacy and safety interpretation, despite the stated endpoint and follow-up period.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia — NCT00453388.
- Registry record last updated 2020-01-29; status last verified 2019-12.
- Results first posted 2017-05-24.
- 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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19. Record Summary
The registry describes NCT00453388 as a completed, phase II, nonrandomized, parallel dose-finding study sponsored by Fred Hutchinson Cancer Center. Enrollment is listed as 6; the recorded start is 2007-02 and primary completion is 2013-06. The study evaluated a nonmyeloablative donor bone marrow transplant strategy involving fludarabine phosphate, cyclophosphamide, total-body irradiation, mycophenolate mofetil, and cyclosporine.
The primary outcome was the number of patients who engrafted at each irradiation dose, defined as greater than 95% donor chimerism and assessed up to Day 200. The registry does not report the engraftment results by dose or any primary outcome analysis. It reports descriptive adverse-event counts for Arms II and III and states that no subjects meeting the criteria for Arms I or IV were enrolled.
The record does not provide a sample-size justification, complete analysis plan, primary analysis population, or missing-data methods. Its nonrandomized arms are not like-for-like controls, limiting direct comparisons.