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 Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease (NCT04207320), a non-randomized na study. The primary outcome is Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04207320 |
| Phase | NA |
| Condition | Sickle Cell Disease |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Chicago |
| Results posted | Yes |
2. Clinical Question
Population
The intended population was children and adolescents with severe sickle cell disease who were eligible for haploidentical hematopoietic stem cell transplantation. Stage I was intended for eligible subjects between the ages of 10-25 years; Stage II was intended for eligible subjects between the ages of 2-25 years. The record reports enrollment of 3, but says that no subjects underwent transplant and that all subjects were withdrawn before study procedures or outcome measures were performed.
Intervention
The intervention was αβ+ T-cell depletion with the Miltenyi CliniMACS system in the setting of haploidentical hematopoietic stem cell transplantation. The study’s stated purpose was to assess the safety of this transplant approach for severe sickle cell disease. The record does not report that the intervention was administered to any subject.
Comparator
The study was non-randomized and sequential, with Stage I and Stage II described as successive stages rather than like-for-like control arms. No randomized or concurrent control group is described. The stages had different eligibility age ranges, so a comparison between them would not by itself isolate an intervention effect.
Primary question
The intended primary question was whether the transplant approach could be assessed for safety by measuring graft failure, grade III/IV irreversible end-organ toxicity, grade III/IV acute graft-versus-host disease (aGvHD), or death within 100 days post-Hap-HSCT. Because no subject underwent transplant and no outcome measures were performed, the registry record cannot answer that safety question.
3. Trial Design
The registry record describes a non-randomized, unmasked, sequential study of hematopoietic stem cell transplantation for patients with severe sickle cell disease. Its title specifies haploidentical transplantation using myeloablative conditioning and αβ+ T-cell-depleted hematopoietic stem cells from partially matched familial donors. The listed intervention is αβ+ T-cell depletion with the Miltenyi CliniMACS system, classified in the record as a device.
The study was organized into Stage I and Stage II. Stage I was intended to include eligible subjects between the ages of 10-25 years, while Stage II was intended to include eligible subjects between the ages of 2-25 years. The record describes a sequential model, but does not report the operational rules for moving between stages, nor does it report a statistical plan for comparing them. The stages should not be treated as randomized comparison groups: allocation was non-randomized, and the record does not describe a like-for-like control arm.
The listed phase is NA. Enrollment is reported as 3. The study start date is 2020-04-07, and the primary completion date is 2023-05-22. Its status is terminated. The record does not report the reason for termination, so no explanation for the closure can be inferred from these details.
The most consequential design fact is that the study closed before transplantation or outcome assessment. The registry states that all subjects were withdrawn and that no subjects underwent transplant while on study. Thus, the intended treatment strategy and safety endpoint were not evaluated in participants who received the transplant. The record reports no analysis results, and does not describe a completed comparison of stages or any other study groups.
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 | Stage I | Stage II |
|---|---|---|
| STARTED | 3 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: No subjects underwent transplant while on study. All subjects withdrawn and study closed prior to any study procedures/outcome measures performed.
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: Stage II never opened at our site
| Characteristic | Unit | Stage I | Stage II | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 0 | 3 | |
| Age, Categorical: <=18 years | Participants | 1 | 0 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 0 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 20 (16 to 22) | — | 20 (16 to 22) |
| Sex: Female, Male: Female | Participants | 2 | 0 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 0 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | — | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT, measured over 100 days post-Hap-HSCT.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The intended primary endpoint was safety within 100 days post-Hap-HSCT. It was defined by the occurrence of graft failure, grade III/IV irreversible end-organ toxicity, grade III/IV aGvHD, or death during that timeframe. This is a composite endpoint: several distinct clinical events are combined into a single safety outcome. A composite can capture more than one kind of adverse outcome, but its interpretation depends on knowing which component occurred and how each component was defined and assessed.
The record describes graft function using stable donor engraftment, defined as >5% total nucleated cell DNA, and donor erythropoiesis that corrects the sickle cell disease hematologic phenotype, described as <50% HbS in peripheral blood. It describes organ toxicity as grade III/IV irreversible end-organ toxicity based on NCI grading, and graft-versus-host disease as grade III/IV aGvHD. These definitions specify what the intended assessments concerned; they are not observed endpoint results.
A safety endpoint of this kind is used to organize assessment of serious outcomes associated with a transplant strategy. However, the registry states that no subjects underwent transplant and that no outcome measures were performed. The endpoint therefore has no observed study value in this record. It cannot establish an event rate, describe the timing or type of any event, or quantify uncertainty about safety.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted results do not provide an estimate of the primary safety endpoint. The registry record states that no subjects underwent transplant while on study, all subjects were withdrawn, and study closure occurred before procedures or outcome measures were performed. Consequently, there are no observed transplant recipients in this study from whom the specified 100-day outcomes could be assessed.
The adverse-event fields list zero subjects at risk, zero affected subjects, and zero deaths for both Stage I and Stage II. Those entries should not be interpreted as evidence that no serious adverse events occurred among treated participants. The record explicitly reports that no subjects underwent transplant, and the listed at-risk counts are zero. With no transplant exposure and no outcome assessment, these fields do not provide a denominator for estimating the incidence of transplant-related events. They describe the absence of evaluable participants in the reported adverse-event data, not demonstrated absence of harm.
Enrollment is reported as 3, but enrollment alone does not indicate that transplantation occurred, that the intended treatment was received, or that endpoint follow-up was completed. In this record, the stated population description directly clarifies that all subjects were withdrawn before procedures or outcome measures. The enrollment figure therefore cannot be used to infer an analyzed population or to calculate an event rate.
The study’s non-randomized, sequential design also matters to interpretation. Stage I and Stage II were not assigned through randomization, and no like-for-like control group is described. Their age eligibility ranges differ. Even if outcome data had been available, a simple difference between stages would not automatically identify an intervention effect; interpretation would depend on the design, measured outcomes, and analysis approach. The registry does not report a statistical analysis plan, and the analysis count is 0.
No confidence interval, p-value, effect estimate, or inferential comparison is reported for the primary endpoint. A confidence interval is a statistical way to express precision around an estimated quantity; without an observed endpoint estimate, there is no study-specific interval to interpret. Likewise, a significance test cannot answer the safety question without measured outcomes and a defined analysis. The absence of such results is not evidence of equivalence, safety, or lack of effect.
The registry status is terminated, but the reason for termination is not reported in the registry record. The listed study dates and status establish the record’s timeline and closure status, not why the study ended. Any explanation involving recruitment, safety, feasibility, funding, or a protocol decision would be speculation.
9. Statistical Methods Explained
What does the study design permit?
A non-randomized study does not assign participants to groups by chance. This can be appropriate for describing an intended clinical approach, but it means that group comparisons may be affected by differences in eligibility, timing, clinical characteristics, or care. Randomization is one method of balancing measured and unmeasured factors on average; it is not reported for this study. The record instead describes a sequential model with Stage I and Stage II. These stages have different eligibility age ranges and are not described as randomized arms or as a control comparison.
Masking is listed as none. Masking means keeping treatment assignment or other study information from participants, clinicians, or assessors, depending on the design. The record does not describe further masking details. In general, lack of masking can affect how outcomes are reported, managed, or assessed, especially when outcomes require judgment. That general concern does not establish that any such bias occurred in this study, since the record says no outcome measures were performed.
What does the composite endpoint represent?
The primary endpoint combines graft failure, grade III/IV irreversible end-organ toxicity, grade III/IV aGvHD, or death within 100 days post-Hap-HSCT. A composite endpoint treats the occurrence of any specified component as meeting the endpoint. This can make a safety assessment cover multiple clinically important event types, but a single composite result may obscure which component drives the result. Component-level reporting helps distinguish, for example, graft-related outcomes from organ toxicity or death. Here, neither a composite result nor component results are available because no subjects underwent transplant and the record says outcomes were not measured.
The endpoint description also includes definitions for graft function. Stable donor engraftment is specified as >5% total nucleated cell DNA, with donor erythropoiesis described as correcting the sickle cell disease hematologic phenotype at <50% HbS in peripheral blood. Such criteria make an endpoint more operational by stating what would count as evidence of graft function. They do not represent observed measurements in this study. The record’s statement that no transplant occurred takes precedence over treating these criteria as achieved or assessed outcomes.
Why are denominators essential?
An event rate requires an appropriate denominator: the number of participants who were exposed to the relevant intervention and had a meaningful opportunity for the event to be observed. The adverse-event entries report zero at risk for both stages, and the record says there were no transplant recipients. The zero entries therefore cannot be read as event-free follow-up among treated participants. Without a relevant denominator and outcome assessment, an incidence estimate cannot be calculated or interpreted.
In general, missing outcome data can create uncertainty because it may be unclear whether participants experienced an event, were not assessed, or were no longer followed. This record provides a more specific statement: all subjects were withdrawn, no subjects underwent transplant, and no outcome measures were performed. It does not report a plan for handling missing observations because no statistical analysis is reported. It would be inappropriate to impute outcomes or assume that withdrawal implies either an event or no event.
What can significance tests and confidence intervals tell us?
In general, a significance test evaluates how compatible observed data are with a specified statistical model or null hypothesis. A p-value does not measure the size or clinical importance of an effect, and it is not the probability that a treatment works. A confidence interval describes uncertainty around an estimate under the assumptions of the method used. These tools require relevant observed data and a defined analysis. The registry reports 0 analyses and no endpoint measurements, so there is no study-specific p-value, confidence interval, or treatment effect to interpret.
The record’s planning note describes a sample-size illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the target effect as a stated fraction of an observed effect, with time-to-event illustrations expressed as total events and other illustrations as participants per arm. Such planning calculations are not observed study outcomes and are not observed power. Because the registry reports no transplant outcomes or analysis, the posted results do not establish an observed study effect to use as a basis for interpreting a trial-specific illustration. The record does not report that these planning assumptions were the study’s own design or that they were used to justify enrollment.
How should multiplicity be considered?
Multiplicity arises when an analysis addresses multiple outcomes, comparisons, or statistical tests. Without an adjustment or a prespecified hierarchy, repeated testing can increase the chance of finding an apparently notable result by chance. The registry lists secondary outcomes concerning overall and event-free survival, acute and chronic GvHD, and severe forms of acute and chronic GvHD. It does not report a multiplicity strategy, a hierarchy among outcomes, or an analysis plan. Since no analyses were performed, there are no reported tests whose multiplicity can be evaluated. The appropriate conclusion is that the planned handling of multiple outcomes is not reported in the registry record.
Time-to-event methods, such as those referenced in the general planning note, account for the time until an event and can accommodate differing follow-up periods under their assumptions. Their interpretation depends on event counts, follow-up, censoring, and the analysis specification. None of these study-specific outcome data are reported for this trial. General methodological descriptions cannot substitute for an analysis of actual transplant follow-up.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes for 1-year overall and event-free survival after Hap-HSCT, incidence of Grades I Through IV acute GvHD, severe acute GvHD as Grades III Through IV, Grades I Through IV chronic GvHD, and severe chronic GvHD as Grades III and IV. The record reports 6 outcome measures, but does not provide results for those measures. No subjects underwent transplant, and no outcome measures were performed.
A multiplicity strategy addresses the interpretive problem created by examining multiple outcomes or comparisons. The registry does not report whether outcomes were prioritized, whether any testing hierarchy was planned, or whether statistical adjustments were intended. The number or identity of analyses planned for each outcome is not described; the record reports 0 analyses. Therefore, there are no statistical tests to assess for multiplicity, and the planned approach is not reported in the registry record.
The registry states that all subjects were withdrawn and that there were no study procedures or outcome measures. It does not report why subjects were withdrawn, what follow-up was available before withdrawal, or a missing-data method. It would not be appropriate to assume that missing outcomes represent event-free status, or to impute events from the adverse-event fields. Because no subjects underwent transplant, the record also does not establish a treated analysis population or an evaluable population for the primary endpoint.
In general, analysis populations should be defined in advance, and the treatment of incomplete follow-up should be described so readers can understand which participants contribute to each estimate. The registry record does not report those details. Its explicit statement that outcomes were not measured means the main issue is not simply incomplete endpoint data among treated participants; the intended transplant outcome assessment did not take place.
11. What the Result Does, and Does Not, Mean
The record establishes that this study was registered as an investigation of haploidentical hematopoietic stem cell transplantation for severe sickle cell disease, with safety assessed through specified events during 100 days post-Hap-HSCT. It also establishes that the study was terminated, enrollment was reported as 3, and no subjects underwent transplant while on study. All subjects were withdrawn before study procedures or outcome measures were performed.
These registry entries do not provide evidence about the frequency of graft failure, severe irreversible organ toxicity, severe acute GvHD, or death after this transplant approach. There are no observed outcomes from which to estimate those risks in this study. The zero adverse-event counts are accompanied by zero participants at risk and must not be interpreted as proof that the intervention had no serious adverse events. There is no basis for an efficacy estimate, a safety estimate, or a comparison with an alternative approach.
The record also does not show that the study’s aims were met or that a particular clinical result prompted termination. The reason for termination is not reported in the registry record. Likewise, the stated enrollment does not establish treatment receipt or completed follow-up; the record explicitly says the opposite for transplantation and outcome measurement.
In general, a study that does not reach outcome assessment cannot resolve its intended clinical question. This is a limitation of the available evidence, not a finding that the intervention is beneficial, harmful, equivalent to another strategy, or ineffective. The record can inform readers about the intended design and the fact that outcome data were not generated, but it cannot support conclusions about transplant outcomes.
12. Why This Trial Matters Statistically
This record illustrates why the distinction between enrollment and treatment exposure is essential when interpreting clinical trial data. Enrollment is reported as 3, but no subjects underwent transplant and no outcome measures were performed. For the intended safety endpoint, the relevant information would be outcomes among participants who received the transplant and had assessment during the specified follow-up period. The record contains no such observations.
It also illustrates why zero event entries should be interpreted alongside their denominators. The adverse-event fields show zero at risk and zero affected subjects for both stages. With no participants at risk of the transplant-related outcomes, those entries cannot be taken as evidence that the outcomes did not occur after treatment. An empty or non-evaluable safety dataset is not the same as observed event-free follow-up.
The design details matter as well. The record describes a non-randomized, sequential study, not a randomized comparison. Stage I and Stage II had different age eligibility ranges, and no like-for-like control group is described. Thus, even if results had been available, readers would need to distinguish descriptive safety information from causal comparisons between groups.
Statistically, a study’s intended endpoints, analysis plans, and observed results serve different purposes. The endpoint definitions describe what the investigators intended to measure. The record’s sample-size note describes general planning assumptions. Neither supplies observed clinical outcomes. Here, no analyses are reported, so estimates and uncertainty measures cannot be reconstructed from the registry information.
The main statistical lesson is one of evidence boundaries: registration and planned measurement alone do not answer an outcome question. The registry supports a clear account of what was intended and why no endpoint estimate is available, while leaving the clinical safety question unresolved by this study.
13. 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 principal trial-specific limitation is that the intended treatment and endpoint assessment did not occur. The registry states that no subjects underwent transplant, all subjects were withdrawn, and no procedures or outcome measures were performed. As a result, the primary safety outcome and listed secondary outcomes have no observed study results. No event rate, survival estimate, treatment effect, or confidence interval can be derived from this record.
The record reports enrollment of 3, but does not describe the disposition of subjects in detail beyond withdrawal before study procedures or outcome measurement. The reason for withdrawal and the reason the study was terminated are not reported in the registry record. It is therefore not possible to determine from these data why the study closed or whether the reason relates to recruitment, feasibility, safety, or another matter.
The design was non-randomized and sequential, with two stages that had different eligibility age ranges. No like-for-like control comparison is described. The record does not report procedures for stage progression or a statistical analysis plan, so the intended approach to comparisons and inference cannot be assessed.
The primary endpoint is a composite of multiple serious outcomes. The record specifies endpoint components and graft-function criteria, but no component-level results are available. The registry does not report a multiplicity strategy, missing-data method, or analysis-population definitions. These limitations concern what can be assessed from the record; they do not establish that any particular method was or was not used outside what the registry reports.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease — NCT04207320.
- Registry record last updated 2024-12-04; status last verified 2024-11.
- Results first posted 2024-12-04.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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17. Record Summary
This record concerns NCT04207320, a study of haploidentical hematopoietic stem cell transplantation for patients with severe sickle cell disease. The listed intervention was αβ+ T-cell depletion with the Miltenyi CliniMACS system. The study was non-randomized, unmasked, and sequential, with Stage I intended for eligible subjects between the ages of 10-25 years and Stage II for eligible subjects between the ages of 2-25 years.
The registry reports enrollment of 3, a start date of 2020-04-07, a primary completion date of 2023-05-22, and terminated status. Its intended primary endpoint concerned graft failure, grade III/IV irreversible end-organ toxicity, grade III/IV aGvHD, or death within 100 days post-Hap-HSCT.
No subjects underwent transplant; all were withdrawn, and no outcome measures were performed. The record reports 0 analyses and provides no results for the intended safety endpoint. The reason for termination is not reported in the registry record.