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 Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation (NCT04339101), a na phase 2 study. The primary outcome is Graft-versus-host Disease Free Relapse Free (GRFS) at 1 Year.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04339101 |
| Phase | Phase 2 |
| Condition | Acute Leukemia, Hematologic and Lymphocytic Disorder, Myelodysplastic Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | City of Hope Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with acute leukemia, myelodysplastic syndrome, or myelofibrosis undergoing reduced-intensity conditioning donor stem cell transplantation. The registry record also lists hematologic and lymphocytic disorder among the conditions.
Intervention
Itacitinib added to tacrolimus and sirolimus for GVHD prophylaxis, with fludarabine and melphalan as the conditioning regimen.
Comparator
No separate comparator group is listed. The study is described as single-group, and allocation is recorded as NA.
Primary question
What is the probability of remaining free of the specified severe GVHD events, chronic GVHD requiring systemic treatment, relapse, and death through 1 year after transplantation?
The study addresses a post-transplant outcome in a population with several underlying blood cancers or disorders. Its primary endpoint, GVHD-free relapse-free survival (GRFS), combines clinically distinct events into a measure of time until the first qualifying event. The registry defines those events as grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death.
The clinical question concerns the outcome observed in patients receiving the three-drug prophylaxis regimen in this study. It is not a direct comparison of that regimen with tacrolimus and sirolimus alone, or with another prophylaxis strategy: no control arm is listed. The design therefore cannot, on its own, separate the regimen's association with outcomes from other influences on post-transplant results.
The registry record does not report the observed GRFS estimate or its 95% confidence interval. It therefore does not establish the magnitude or precision of the outcome for this study population. The record describes the intended question and endpoint, but the posted results do not give the primary endpoint result needed to answer it quantitatively.
3. Trial Design
This is a completed Phase IIa study sponsored by City of Hope Medical Center. The registry lists a single-group model, no masking, and allocation as NA. Enrollment is recorded as 59. The study began on 2020-11-05, reached primary completion on 2023-05-22, and has a status of completed.
Participants were patients with acute leukemia, myelodysplastic syndrome, or myelofibrosis undergoing reduced-intensity conditioning donor stem cell transplantation. The regimen description names fludarabine, melphalan, itacitinib, tacrolimus, and sirolimus. Fludarabine is described as being given by infusion on days -9 to -5, with melphalan on day -4, followed by allogeneic hematopoietic cell transplantation on day 0. Itacitinib is described as oral once daily from day -3. The registry text cuts off while describing how long itacitinib continues; the complete duration and detailed administration schedules for tacrolimus and sirolimus are not reported in the registry record.
The primary endpoint is GRFS at 1 year after transplant. The record also names cumulative incidence of grade II-IV acute GVHD and progression-free survival as secondary outcomes. It states that a Kaplan-Meier curve will be generated for GRFS, but the registry record does not report the resulting estimate, confidence interval, or numerical results for the secondary outcomes.
A single-group design describes outcomes among participants who received the study regimen; it does not provide a concurrent randomized control group. Because masking is listed as none, the study is unmasked. The registry record does not report a protocol-based sample-size justification, detailed eligibility criteria, or a fuller statistical analysis plan. The enrollment of 59 should not be read as evidence that a particular level of statistical precision or power was achieved.
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 (Itacitinib Adipate, Tacrolimus, Sirolimus) |
|---|---|
| STARTED | 59 |
| COMPLETED | 59 |
| 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.
| Characteristic | Unit | Treatment (Itacitinib Adipate, Tacrolimus, Sirolimus) |
|---|---|---|
| Participants analysed | 59 | |
| Age, Continuous | years | 63 (23 to 75) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 36 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 10 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 48 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Graft-versus-host Disease Free Relapse Free (GRFS) at 1 Year, measured over From the date of transplantation to the first time of observing following events: grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first, assessed at 1 year post transplant..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of probability |
| Endpoint classification | not reduced to a single comparison |
GRFS is a time-to-event composite endpoint. The registry defines the time origin as the date of transplantation and the event as the first occurrence of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. The primary outcome is the probability of GRFS at 1 year, expressed as a percentage, with a 95% confidence interval specified as the measure of uncertainty.
A composite endpoint can represent several important ways a participant may experience an unfavorable post-transplant course. It can also make an outcome more frequent than any single component because several types of event qualify. The composite does not mean that the components are interchangeable: the experience and clinical implications of GVHD, relapse, and death differ. An overall GRFS estimate alone would not show which component contributed most to the observed events. Component-specific results would be needed for that distinction.
The registry states that a Kaplan-Meier curve will be generated for GRFS. In general, Kaplan-Meier methods use the observed timing of events and account for participants whose follow-up ends before an event is recorded. The posted record does not include the GRFS estimate or confidence interval, so neither the event-free probability at 1 year nor its precision can be described from the available results. Details about censoring and handling of competing events are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes that this was a completed, single-group Phase IIa study with enrollment of 59 and a primary endpoint defined as GRFS at 1 year after transplantation. It does not report the observed primary endpoint value or its 95% confidence interval. As a result, the posted results do not permit a quantitative interpretation of the primary outcome's level or precision.
The endpoint definition is important when considering what a future estimate would mean. GRFS counts time until the first of several events: grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. A result for the composite would summarize the probability of avoiding any of these events through the stated assessment time. It would not by itself reveal how many participants experienced each component or which event type chiefly shaped the composite result. Those component-specific results are not reported in the registry record.
The single-group design also limits the interpretation. The study describes outcomes in patients receiving itacitinib with tacrolimus and sirolimus, but it does not list a concurrent group receiving a different regimen. There is therefore no randomized, like-for-like comparison in this record from which to estimate a difference between strategies. Outcomes observed in the study cannot be attributed to the added itacitinib on the basis of this design alone.
The registry names cumulative incidence of grade II-IV acute GVHD and progression-free survival as secondary outcomes, but their numerical results are not reported in the registry record. It also lists adverse-event counts and selected serious adverse-event terms. These safety entries describe recorded events in the study group; without further information on timing, attribution, duration, and event definitions, they do not establish whether an event was caused by a study drug.
Precision cannot be judged without the primary estimate and its interval. Enrollment of 59 is not a substitute for those results, and it does not show how many participants contributed information at the 1-year assessment. The registry record does not report the number analyzed for GRFS, the amount of follow-up, or the number censored. Thus, the record supports a description of the trial design and endpoint, but not a conclusion about the magnitude of GRFS or a comparative treatment effect.
9. Statistical Methods Explained
The registry describes a Kaplan-Meier analysis for the primary GRFS endpoint and specifies a 95% confidence interval. The registry record does not provide numerical output from that analysis, nor does it describe several implementation details needed to reproduce or fully assess it. The following explains the statistical ideas in general and distinguishes them from methods specifically documented for this study.
What does a time-to-event endpoint represent?
In general, a time-to-event endpoint records both whether a qualifying event occurs and how long it takes to occur. For GRFS, the registry starts the clock on the transplant date and defines the event as the first occurrence of any listed component. A participant who experiences more than one qualifying event contributes the time of the first one to this composite endpoint. The endpoint is therefore not simply a count of events, nor is it a measure of the duration of each component.
The definition of the event matters. Grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, and death are grouped together for the primary outcome. In general, a composite can provide a single summary of time free from a range of events, but it can obscure variation among its components. To understand the contribution of each event type, component-specific counts or estimates are useful. Such primary-component results are not reported in the registry record.
What does Kaplan-Meier estimation do?
In general, Kaplan-Meier estimation uses event times to estimate the probability of remaining event-free over time. It can include participants whose observation ends before an event, provided their follow-up status is handled as censoring under the analysis approach. Censoring means that the event time is not observed during the available follow-up; it does not mean that the participant experienced no event at any later time.
The record says a Kaplan-Meier curve will be generated for GRFS and gives the assessment time as 1 year. It does not report the estimated probability at that time, the confidence interval limits, the number at risk over follow-up, or the censoring rules. Without these, readers cannot assess how much information supports the estimate at later follow-up or reproduce the calculation.
Death is included as a GRFS event, not treated as a competing event for this composite definition. For other endpoints, competing risks can matter when an event of interest may be precluded by a different event. In general, cumulative-incidence methods account for that structure differently from Kaplan-Meier methods that censor competing events. The registry lists cumulative incidence of grade II-IV acute GVHD as a secondary outcome, but it does not report the methods used to calculate that endpoint or its result. The approach to competing events for the secondary outcome is not reported in the registry record.
How should a confidence interval be read?
In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider interval for the same quantity and method; it does not show that an estimate is unbiased, that the design supports a causal conclusion, or that the outcome is clinically important. Here, the registry specifies a 95% confidence interval for GRFS but does not report its limits. Therefore, the precision of the primary estimate cannot be evaluated.
A confidence interval also does not replace examination of the study design. Even a precisely estimated outcome in a single group would describe that group's observed experience, not a randomized contrast with another regimen. The absence of a control arm is a design limitation that an interval around a single-group estimate cannot resolve.
What can and cannot be inferred from the sample size?
The registry records enrollment of 59, but this does not establish the number included in each endpoint analysis or the number with complete follow-up. The number analyzed for GRFS, withdrawals, exclusions, and missing outcome data are not reported in the registry record. Enrollment alone cannot show whether the estimate is precise, whether the study achieved a target, or whether participants who were not fully observed differed from those with complete information.
General sample-size planning uses assumptions about the target effect, variability or event rate, significance level, allocation, and analysis method. A planning calculation is a hypothetical design aid, not an observed result and not a measure of the study's observed power. The registry record does not report the trial's own sample-size justification or planned target assumptions. It also does not report interim analyses or stopping rules. Those details should not be inferred from the enrollment count or from the presence of an endpoint estimate in any separate planning illustration.
Why does the study design affect statistical interpretation?
The study is listed as single-group, with allocation recorded as NA and masking as none. General statistical comparisons between treatment groups require data from groups and a defined contrast. Since this record lists no concurrent comparator, it does not support a randomized estimate of the difference between the study regimen and another prophylaxis approach. Patient characteristics, disease mix, transplant factors, and follow-up can all shape observed outcomes; the record does not provide an adjusted comparative analysis to address such factors.
Consequently, the most defensible statistical description is limited to the study's design, endpoint definition, enrollment, and reported safety counts. The primary estimate and its uncertainty, analytic population, missing-data approach, and detailed modeling choices are not reported in the registry record. These omissions prevent a fuller assessment of the primary outcome's precision and robustness.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies GRFS at 1 year as the primary endpoint and names cumulative incidence of grade II-IV acute GVHD and progression-free survival as secondary outcomes. It does not report numerical results for the primary endpoint or the secondary outcomes. No multiplicity adjustment or hierarchy for interpreting multiple outcomes is reported in the registry record.
In general, evaluating multiple endpoints can increase the chance of a chance finding if each is tested and interpreted separately. A prespecified hierarchy or adjustment can help define how evidence across endpoints is assessed. The registry record does not report whether any such strategy was planned or used. It also does not report the inferential tests, significance thresholds, or whether any outcomes were treated as exploratory.
The record does not describe missing-data methods, censoring rules, or the analysis population used for GRFS or the secondary outcomes. It does not report how many participants were included in each analysis, whether all enrolled participants were analyzed, or how incomplete follow-up was handled. Enrollment of 59 should not be treated as the endpoint denominator without an explicit analysis population.
The record lists zero analyses. That entry does not establish that no analyses were conducted; it means the registry record does not list analysis records. The statistical analysis plan, interim analyses, and sample-size justification are not reported in the registry record. Without these details and the outcome results, readers cannot evaluate how the analyses relate to prespecified plans, how missing observations were handled, or how multiplicity affected interpretation.
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 (Itacitinib Adipate, Tacrolimus, Sirolimus) | 9 | 59 | 15.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Itacitinib Adipate, Tacrolimus, Sirolimus) | 14 of 59 |
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 (Itacitinib Adipate, Tacrolimus, Sirolimus) | 59 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Itacitinib Adipate, Tacrolimus, Sirolimus) |
|---|---|---|
| GI Bleed | Gastrointestinal disorders | 2 of 59 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 2 of 59 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 59 |
| E. Faecalis Bactermia | Blood and lymphatic system disorders | 1 of 59 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 59 |
| GI Bleed | Blood and lymphatic system disorders | 1 of 59 |
| polymicrobial pneumonia | Blood and lymphatic system disorders | 1 of 59 |
| Cardiac Failure | Cardiac disorders | 1 of 59 |
| Intermittent | Gastrointestinal disorders | 1 of 59 |
| Disease progression | General disorders and administration site conditions | 1 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Itacitinib Adipate, Tacrolimus, Sirolimus) |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 55 of 59 |
| Platelet count decreased | Investigations | 55 of 59 |
| Nausea | Gastrointestinal disorders | 52 of 59 |
| Anemia | Blood and lymphatic system disorders | 51 of 59 |
| White blood cell decreased | Investigations | 51 of 59 |
| Hypomagnesemia | Metabolism and nutrition disorders | 51 of 59 |
| Lymphocyte count decreased | Investigations | 48 of 59 |
| Neutrophil count decreased | Investigations | 48 of 59 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 46 of 59 |
| Hypocalcemia | Metabolism and nutrition disorders | 46 of 59 |
Serious events with the highest arm-level rate: gi bleed (3.4%), hypoxia (3.4%), respiratory failure (3.4%), e. faecalis bactermia (1.7%), febrile neutropenia (1.7%).
The adverse-event record lists 59 participants at risk for serious adverse events and 9 affected. It lists 59 participants at risk for other adverse events and 59 affected. The record also lists 14 deaths. These are counts recorded for the study group; they should not be interpreted as evidence that the regimen caused the events or deaths. The registry record does not report the relationship of each event or death to a study drug.
The selected serious adverse-event terms include GI Bleed, Hypoxia, and Respiratory failure, each listed as 3.4%, and E. Faecalis Bactermia, Febrile neutropenia, and polymicrobial pneumonia, each listed as 1.7%. These entries identify terms and reported percentages, but the record does not provide additional context such as onset, duration, resolution, severity grading beyond serious-event status, or whether one participant could contribute to more than one term.
Counts of affected participants are not necessarily counts of distinct event episodes. The record's labels do not explain the event-counting rules, exposure time, or follow-up period for the safety summaries. The 14 deaths are not described as treatment-related or unrelated, and the registry record does not report their timing or causes. Safety figures should therefore be read as descriptive entries for this group, not as comparative rates or causal estimates.
12. What the Result Does, and Does Not, Mean
The study asks a clinically relevant question about GRFS after reduced-intensity conditioning donor stem cell transplantation in patients with acute leukemia, myelodysplastic syndrome, or myelofibrosis. The regimen combines itacitinib with tacrolimus and sirolimus, alongside fludarabine and melphalan conditioning. The registry's primary endpoint is clearly defined as time from transplant to the first of several serious clinical events, assessed at 1 year.
The key limitation for interpreting the result is that the registry record does not report the primary GRFS estimate or its 95% confidence interval. It also does not report the numerical findings for its named secondary outcomes. As a result, the posted results do not quantify the probability of GRFS in this study or how precisely it was estimated. Absence of a result from the record does not mean that no events occurred or that the endpoint was not assessed.
Because the trial is single-group and unmasked, its design does not create a like-for-like comparison with another prophylaxis regimen. Even if a numerical outcome estimate were reported, it would describe observed outcomes among study participants rather than establish the effect attributable to adding itacitinib. The safety counts are also descriptive and do not establish drug causation.
The record is informative about the study's design, population, regimen components, endpoint definition, and some safety entries. It is not sufficient to establish comparative effectiveness, explain which GRFS component drove outcomes, or assess the precision of the primary result. The missing analysis details, endpoint denominators, and follow-up information further limit assessment. Conclusions should remain confined to what the registry reports rather than extending to a treatment recommendation or a claim of benefit or harm.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly named endpoint is not enough for statistical interpretation. The GRFS definition specifies the time origin, the qualifying events, and the assessment time, giving readers a framework for understanding the intended outcome. Yet without the estimated probability and its confidence interval, the registry record does not communicate the level or precision of that outcome.
It also highlights the distinction between estimating an outcome in a treatment group and estimating a treatment effect. A single-group study can describe the experience of participants receiving a regimen, but it has no concurrent randomized comparison in this record. The presence of a numerical endpoint, if available, would not by itself answer whether outcomes differ from those under another strategy.
The composite endpoint raises a further statistical issue: one summary can combine multiple types of events while concealing their individual contributions. Reporting component-specific information alongside the composite can help readers understand what the overall result represents. Those component-specific primary endpoint results are not reported in the registry record.
Finally, enrollment and adverse-event counts are not substitutes for a complete outcome analysis. Statistical interpretation also depends on analytic denominators, follow-up, censoring, missing-data methods, and the plan for interpreting multiple outcomes. The record's omissions make those considerations visible as essential parts of transparent trial reporting, rather than details that can safely be assumed.
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 important limitation for interpreting this trial is the single-group design. Allocation is recorded as NA, and no control arm is listed, so the study cannot supply a randomized comparison with another GVHD prophylaxis regimen. Masking is listed as none, which also means outcome assessment was not masked according to the registry record. The extent to which this could affect subjective assessments is not reported.
The registry record does not include the primary GRFS estimate or its 95% confidence interval, despite defining the endpoint and stating that a Kaplan-Meier curve will be generated. Numerical results for the named secondary outcomes are also not reported. The number analyzed for each outcome, follow-up completeness, censoring details, and missing-data procedures are not reported in the registry record. These omissions prevent assessment of precision and the robustness of the estimates.
The population includes several underlying diagnoses, but the record does not provide outcome results by diagnosis or other participant characteristics. It therefore does not show whether outcomes varied across subgroups. The regimen description is incomplete: it cuts off while stating how long itacitinib continues, and detailed schedules for tacrolimus and sirolimus are not reported in the registry record.
Safety information is limited to counts and selected serious adverse-event terms. Event timing, attribution, duration, and detailed definitions are not reported. The registry record also does not report a sample-size justification, interim analyses, a detailed statistical analysis plan, or a multiplicity strategy. These limitations should be considered alongside the enrollment of 59 and the descriptive nature of the available safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation — NCT04339101.
- Registry record last updated 2026-11-03; status last verified 2026-10.
- Results first posted 2023-09-13.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT04339101 is a completed Phase IIa, single-group, unmasked study sponsored by City of Hope Medical Center. The registry records enrollment of 59 and evaluates itacitinib with tacrolimus and sirolimus for GVHD prophylaxis after reduced-intensity conditioning donor stem cell transplantation in patients with acute leukemia, myelodysplastic syndrome, or myelofibrosis.
The primary endpoint is GRFS at 1 year, defined by time to the first of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. The registry states that Kaplan-Meier estimation will be used. It names cumulative incidence of grade II-IV acute GVHD and progression-free survival as secondary outcomes.
The registry record does not report the primary or secondary outcome estimates, the primary confidence interval, analysis denominators, detailed missing-data methods, or a sample-size justification. Safety entries include 9 affected among 59 at risk for serious adverse events, 59 affected among 59 at risk for other adverse events, and 14 deaths. Those entries are descriptive and do not establish causation or comparative effects.