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 Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors (NCT00582816), a na phase 1, phase 2 study. The primary outcome is Grade III or IV GVHD.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00582816 |
| Phase | Phase 1, Phase 2 |
| Condition | Leukemia, Solid Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Wisconsin, Madison |
| Results posted | Yes |
2. Clinical Question
The study was designed to assess the feasibility of reduced-intensity conditioning in haploidentical transplantation and the feasibility and safety of post-transplant natural killer (NK) cell infusions. Its intended population included pediatric patients with recurrent acute lymphoblastic leukemia or acute myeloid leukemia, and patients with high-risk or refractory solid tumors. The registry lists leukemia and solid tumors as conditions.
Population
Pediatric patients with recurrent acute leukemia or high-risk or refractory solid tumors were the intended population described in the study summary. The registry enrollment was 9; the number meeting each disease-specific eligibility description or enrolled in each disease group is not reported in the registry record.
Intervention
The study involved reduced-intensity conditioning, haploidentical transplantation, and post-transplant NK cell infusion. The listed interventions include a Clinimacs Cell Separation System, conditioning chemotherapy, and DLI. The registry record does not provide enough detail to describe the complete treatment sequence or each participant’s actual treatment.
Comparator
There was no separate comparison group: the model is single group, allocation is listed as NA, and masking as none. Outcomes therefore describe participants in the study group rather than a randomized contrast with another treatment.
Primary question
The registered primary endpoint was the number of participants with Grade III or IV graft-versus-host disease (GVHD) by Day 100. The study summary also describes feasibility and safety questions around the transplant approach and NK cell infusions. The primary endpoint result is not reported in the registry record.
This design can describe whether specified events were recorded among the treated group, but it cannot by itself estimate how outcomes would have differed under an alternative treatment. The clinical question is therefore principally about feasibility and safety in this study group, rather than a comparative estimate of treatment effect.
3. Trial Design
The registry describes a Phase 1 and Phase 2, single-group study with no masking. Allocation is listed as NA, and the trial was not a randomized comparison. The sponsor was the University of Wisconsin, Madison. The registry lists enrollment as 9, a start date of 2008-08, primary completion in 2015-08, and status as terminated.
The study summary describes a reduced-intensity conditioning regimen in the setting of haploidentical transplantation for patients with recurrent acute lymphoblastic leukemia, acute myeloid leukemia, and high-risk or refractory solid tumors. It also describes evaluating the feasibility and safety of post-transplant NK cell infusions. Listed interventions include the Clinimacs Cell Separation System, conditioning chemotherapy, and DLI. The record does not provide a full protocol or enough information to reconstruct the treatment received by each participant.
The arm description refers to pre-transplant evaluation and KIR ligand typing, as well as parental KIR genotyping and phenotyping for donor selection. The description in the registry record is incomplete, so the donor-selection process cannot be fully characterized from that text. Secondary outcomes include NK expression levels, the association between parental KIR genotypes and NK cell cytotoxicities, and analysis of NK cell KIR expression over time.
The registry lists 7 outcome measures and 0 analyses. The status is terminated, but the reason for termination is not reported in the registry record. The enrollment figure does not establish how many participants contributed data to every outcome, and outcome-specific analysis populations are not reported in the registry record. These gaps matter when interpreting feasibility, safety, and any outcome summaries.
Because the study has no concurrent control group, its findings cannot separate effects associated with the treatment approach from the natural course of disease, other care, or participant differences. That is a design limitation, not evidence for or against a treatment effect.
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 | Haploidentical Transplant With NK Cell Infusion |
|---|---|
| STARTED | 9 |
| COMPLETED | 6 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Haploidentical Transplant With NK Cell Infusion |
|---|---|
| Engraftment Failure | 3 |
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 | Haploidentical Transplant With NK Cell Infusion |
|---|---|---|
| Participants analysed | 9 | |
| Age, Categorical: <=18 years | Participants | 9 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Grade III or IV GVHD, measured over Day 100.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with Grade III or IV GVHD by Day 100. GVHD is an immune complication after transplantation; the endpoint uses its recorded severity grade and a specified follow-up time to define the event. In this registry record, the endpoint is expressed as a participant count, rather than a time-to-event measure or a continuous measurement.
The description sets out grading criteria for skin, gastrointestinal symptoms, and overall GVHD. For skin, Grade III or IV includes Stage 4, described as generalized erythroderma with bullous formation and/or desquamation. The gastrointestinal criteria refer to diarrhea volume and severe symptoms such as abdominal pain, ileus, or stool with frank blood or melena. The overall grading description also includes bilirubin ranges: Grade III is paired with bilirubin 3.1-15 mg/dl, while Grade IV is paired with bilirubin > 15 mg/dl. The registry text includes further stage-specific thresholds.
A graded safety endpoint can capture clinically serious complications that may be important when assessing the feasibility of a transplant approach. Fixing the assessment time at Day 100 also defines the period relevant to this registered outcome. It does not, by itself, describe complications after that time, establish the cause of an event, or measure antitumor activity. The primary endpoint result and the number of participants assessed at Day 100 are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies Grade III or IV GVHD by Day 100 as the primary endpoint, but it does not report a value for that endpoint. Consequently, the posted record does not establish how many participants met the primary endpoint definition, how many were assessed, or how precisely the event frequency was estimated. No confidence interval or inferential analysis for this endpoint is reported in the registry record.
The safety summary reports 9 participants at risk in the study group and 8 participants with at least one serious adverse event. It reports 0 participants with other adverse events in the corresponding group summary. These are descriptive safety counts; they do not provide a comparison against another group. The serious-adverse-event terms listed include Grade 3 infection at 44.4%, Grade 3 anorexia at 33.3%, Grade 3 diarrhea at 22.2%, Grade 3 GVHD at 22.2%, Grade 2 seizure at 22.2%, and Grade 4 engraftment failure possibly from CMV riemia or inadequate stem cell dose at 11.1%.
The percentages attached to individual terms should not be read as mutually exclusive categories. The record does not state that each participant could contribute only one term, and it does not give enough detail to infer a unique participant count from the listed percentages. Nor do these listed safety terms substitute for the primary endpoint result: the endpoint has a specific Grade III or IV definition and Day 100 time frame, while the safety listing is presented as adverse-event terms. The record does not report the timing, duration, or outcome of each event.
There is no randomized comparator, and no treatment-effect contrast is reported. A single-group description can document observed events in the study group, but it cannot estimate what those participants’ outcomes would have been under another treatment. The small enrollment and the absence of outcome-specific denominators or precision estimates further limit interpretation. Enrollment is not necessarily the denominator for every endpoint; the number assessed for each result is not reported in the registry record.
The trial status is terminated. That status alone does not explain why the study ended, whether planned follow-up was completed, or whether the registered endpoint was analyzed. The reason for termination and the primary endpoint result are not reported in the registry record. Accordingly, the posted information supports a limited description of recorded adverse events, but does not provide a complete statistical assessment of the primary question.
9. Statistical Methods Explained
What does a single-group design estimate?
In a single-group study, outcomes are observed in participants who received the study approach. For a binary endpoint such as the presence or absence of Grade III or IV GVHD by Day 100, a basic description would report the number meeting the definition and the number assessed. A proportion can then summarize the observed frequency, with a confidence interval conveying uncertainty around that estimate. General statistical explanation: a confidence interval is a range of values compatible with the data under the interval’s method and assumptions; it is not a guarantee that the true value lies in the interval.
The registry record identifies the endpoint as a participant count, but does not report the count, an assessed denominator, a proportion, or an interval. It also lists 0 analyses. A count without an appropriate denominator would not give the event frequency among those assessed. Since no endpoint result is reported, no estimate or precision statement can be reconstructed from the registry record.
Why does the absence of a comparator matter?
A comparative trial can estimate a difference between outcomes in treatment groups, subject to its design and analysis. This study is listed as single group, with allocation NA and no masking. There is no randomized control group in the registry record. Therefore, any observed event count would describe the study group, not a contrast attributable to the intervention. A single-group event frequency cannot distinguish treatment-related risk from underlying disease, transplant-related factors, other care, or chance.
What does a binary outcome analysis require?
For a binary outcome, participants are classified according to whether the defined event occurred during the relevant assessment period. The endpoint specifies Grade III or IV GVHD by Day 100. A sound report would clarify the number assessed, how missing outcome assessments were handled, and whether the analysis followed a prespecified population definition. Those details, as well as the primary endpoint result, are not reported in the registry record. General statistical explanation: small datasets often yield imprecise estimates, so counts and uncertainty intervals should be read together rather than treating a point estimate as exact.
How should the safety summaries be read?
The registry presents participants at risk and participants affected by serious and other adverse events, along with selected serious-event terms and percentages. These are descriptive summaries. Event categories may overlap: a participant can experience more than one type of event, and the registry does not state that the listed terms are exclusive. The term percentages should therefore not be added or treated as a partition of all participants. The record does not provide event-level detail, a full account of follow-up, or a comparison group. Deaths are not reported in the registry record.
What can be inferred from the listed analyses?
The registry lists 7 outcome measures but 0 analyses. This means the record does not include analysis entries for those outcomes. It does not establish that no analysis was ever conducted outside the registry, nor does it supply results that can be interpreted statistically. No analysis population, missing-data method, covariate adjustment, hypothesis test, or confidence-interval method is reported in the registry record. The statistical plan is also not reported in the registry record, so it is not possible to assess whether the posted outcomes follow a prespecified analysis strategy.
How should planning illustrations be distinguished from study results?
A planning illustration based on an observed effect is not an observed result and is not observed power. The described illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The description says that participant counts are per arm for outcomes other than time-to-event outcomes. These are assumptions for hypothetical planning calculations, not evidence that the trial enrolled two arms or used those choices in its original design. In particular, this study is registered as single group. Sample-size illustrations cannot replace a report of the primary endpoint, its denominator, or its uncertainty, and they do not establish the study’s original sample-size justification. That justification is not reported in the registry record.
General statistical explanation: over-dispersion arises when observed variability is greater than a model assumes. When present, standard errors based on an under-dispersed model may be too small, making uncertainty appear narrower than warranted. The registry record does not report a model for the primary binary endpoint or a dispersion assessment. This general concept should not be taken to imply that over-dispersion was present or relevant in this trial.
Overall, the statistical information available supports descriptive reading of the adverse-event summaries but not a complete analysis of the primary endpoint. Any stronger conclusion would require results and methods not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures, including the primary endpoint and secondary measures relating to NK expression and KIR characteristics. It lists 0 analyses. The record does not report how the study handled the possibility of multiple outcomes or repeated measurements. A multiplicity strategy, such as a prespecified hierarchy or an adjustment to account for several statistical tests, is not reported in the registry record.
Multiplicity matters when several outcomes are tested: the chance of at least one apparently notable result can increase as the number of tests grows. This is a general statistical consideration, not a claim that any particular test was performed or that any result was significant in this study. Since analysis results and a statistical plan are not reported, it is not possible to determine whether multiplicity was addressed.
The registry record also does not report the number of participants with complete data for each outcome, the number missing, or reasons for missing assessments. The number assessed at Day 100 for the primary endpoint is not reported in the registry record. There is no reported missing-data method, sensitivity analysis, or imputation approach. Without those details, it is not possible to judge whether missing outcomes could have affected the interpretation.
The record does not specify analysis populations, such as whether outcomes were summarized for all enrolled participants, only those who received a transplant, or participants with an available assessment. Enrollment is listed as 9, but that does not establish the denominator for each outcome. The record also does not report exclusions or deviations that might affect who contributed to an analysis.
These omissions limit reproducibility and make it difficult to connect the design, outcome definitions, and any analysis to a complete account of results. They do not show that missing data or multiplicity caused bias; they mean the relevant procedures and their possible effects are 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 |
|---|---|---|---|
| Haploidentical Transplant With NK Cell Infusion | 8 | 9 | 88.9% |
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 |
|---|---|
| Haploidentical Transplant With NK Cell Infusion | 0 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Haploidentical Transplant With NK Cell Infusion |
|---|---|---|
| Grade 3 infection | Infections and infestations | 4 of 9 |
| Grade 3 anorexia | Metabolism and nutrition disorders | 3 of 9 |
| Grade 3 diarrhea | Gastrointestinal disorders | 2 of 9 |
| Grade 3 GVHD | Blood and lymphatic system disorders | 2 of 9 |
| Grade 2 seizure | Nervous system disorders | 2 of 9 |
| Grade 4 engraftment failure possibly from CMV riemia or inadequate stem cell dose | Blood and lymphatic system disorders | 1 of 9 |
| Grade 4 engraftment failure | Blood and lymphatic system disorders | 1 of 9 |
| Death | General disorders | 1 of 9 |
| Grade 3 dehydration | Metabolism and nutrition disorders | 1 of 9 |
| Grade 2 diarrhea | Gastrointestinal disorders | 1 of 9 |
Serious events with the highest arm-level rate: grade 3 infection (44.4%), grade 3 anorexia (33.3%), grade 3 diarrhea (22.2%), grade 3 gvhd (22.2%), grade 2 seizure (22.2%).
The safety summary lists 9 participants at risk for serious adverse events and 8 affected. It lists 9 at risk for other adverse events and 0 affected. The registry also lists selected serious-event terms with percentages: Grade 3 infection, 44.4%; Grade 3 anorexia, 33.3%; Grade 3 diarrhea, 22.2%; Grade 3 GVHD, 22.2%; Grade 2 seizure, 22.2%; and Grade 4 engraftment failure possibly from CMV riemia or inadequate stem cell dose, 11.1%.
These entries describe events recorded in the study group; they are not comparative risks. A participant may have experienced more than one event type, so the term percentages should not be added. The registry record does not specify whether every percentage refers to participants or event episodes, and it does not provide event-level timing or duration. The selected terms are not a full clinical account of each participant’s course.
The serious-event summary is distinct from the primary endpoint. The primary endpoint is Grade III or IV GVHD by Day 100, while the safety list includes a Grade 3 GVHD term without reporting the primary endpoint count or its assessment denominator. Deaths are not reported in the registry record. These summaries should be read as descriptive registry entries, not as a complete evaluation of safety or a comparison with another approach.
12. What the Result Does, and Does Not, Mean
The registry documents a study intended to explore the feasibility and safety of reduced-intensity haploidentical transplantation with post-transplant NK cell infusion in pediatric patients with acute leukemia or high-risk solid tumors. It identifies a primary GVHD endpoint and gives a descriptive safety summary. The record also lists secondary measures related to NK expression and KIR characteristics. These features make the study relevant as an early clinical investigation of a transplant approach and its immune-cell components.
What the record does not establish is the primary endpoint result. It does not report how many participants had Grade III or IV GVHD by Day 100, how many were assessed for that outcome, or an estimate with a measure of precision. The listed serious adverse events provide some descriptive information, but do not constitute a complete report of all clinical outcomes or a comparative safety analysis. No results for antitumor activity are reported in the registry record.
The single-group design also limits what can be concluded. Without a concurrent randomized comparison, observed outcomes cannot show what would have happened to similar participants receiving another approach. The registry record cannot establish that the intervention caused a particular event or outcome, and it cannot provide a comparative treatment effect. The study summary describes aims and potential research value; those aims are not themselves findings.
The enrollment, status, and safety entries should be interpreted within the limits of the information recorded. The reason for termination, the analysis populations, missing-data handling, and statistical plan are not reported in the registry record. These missing details prevent a fuller assessment of how completely the study was conducted and analyzed.
In short, the record identifies the clinical questions and gives selected safety counts and terms, but does not report the primary endpoint result or a complete analysis. It therefore supports a cautious description of the study and its posted safety information, not a conclusion about efficacy or comparative safety.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the difference between a clinically important question and an answerable comparative question. The registry asks about feasibility and safety in a population facing serious diseases, and defines a time-bounded primary endpoint for severe GVHD. Yet the study is single group, so it cannot provide a randomized comparison of outcomes under different treatment strategies. The design determines the kinds of conclusions that can be supported, regardless of how important the clinical aim is.
It also highlights why outcome reporting needs both a numerator and a denominator. The primary endpoint is stated as a count, but its result and the number assessed are not reported in the registry record. Without those details, readers cannot estimate the observed event frequency or assess its precision. A named endpoint is not a substitute for its result.
The adverse-event summary further illustrates the importance of distinguishing participants affected from event terms and percentages. Several terms may apply to the same participant, and the registry does not state that categories are exclusive. Clear reporting of event definitions, denominators, follow-up, and overlap is essential for interpreting safety summaries.
Finally, the registry lists multiple outcomes but no analyses. A transparent statistical plan and accounting of missing data and analysis populations would help readers assess how outcomes were selected and interpreted. The record’s limitations do not erase the value of investigating a challenging clinical approach; they define what can be learned from its posted statistical information. This is a case where careful separation of study aims, observed safety entries, and unreported outcomes is especially important.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting the clinical question is that the primary endpoint result is not reported in the registry record. The number assessed for Grade III or IV GVHD by Day 100, the event count, and an uncertainty estimate are also not reported. The registry therefore does not permit a quantitative interpretation of the primary outcome.
The single-group design has no randomized comparator. It can describe events recorded among participants in the study group, but cannot establish a comparative treatment effect or rule out alternative explanations for observed outcomes. No masking is listed, and the record does not describe outcome-assessment procedures or safeguards against bias.
The enrollment is listed as 9, but the analysis population and outcome-specific denominators are not reported. Missing assessments, exclusions, protocol deviations, and the handling of missing data are not reported in the registry record. The number of participants in each disease group is also not reported, limiting assessment of how the mixed intended population is represented.
The registry lists 7 outcome measures and 0 analyses, while a statistical plan, multiplicity procedures, and analysis methods are not reported. The safety summary has selected serious-event terms, but the record does not give event-level timing, duration, outcomes, or a complete account of follow-up. Deaths are not reported in the registry record. The reason the trial was terminated is not reported, so termination cannot be interpreted as evidence about feasibility or safety.
These are limits of the registry record, not proof that an analysis was never conducted or that an unreported outcome was absent. They mean that the posted information is insufficient for a complete assessment of the primary endpoint, study conduct, or overall benefit-risk profile.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors — NCT00582816.
- Registry record last updated 2019-12-09; status last verified 2017-07.
- Results first posted 2017-07-19.
- 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
NCT00582816 is registered as a Phase 1 and Phase 2, single-group study of reduced-intensity haploidentical transplantation with NK cell infusion for pediatric acute leukemia and high-risk solid tumors. The registry lists enrollment as 9, no masking, and status as terminated. The sponsor is the University of Wisconsin, Madison.
The primary endpoint is the number of participants with Grade III or IV GVHD by Day 100. Its result is not reported in the registry record. The safety summary lists 8 participants with serious adverse events among 9 at risk and 0 participants with other adverse events among 9 at risk. Selected serious-event terms and percentages are also listed.
The registry lists 7 outcome measures and 0 analyses. The reason for termination, the primary endpoint denominator, analysis populations, missing-data methods, and statistical plan are not reported in the registry record. The single-group design does not provide a randomized comparison.