Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation (NCT00189488), a randomized phase 2 study. The primary outcome is Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD).

2. Clinical Question

The study asked whether palifermin could reduce severe acute GVHD and severe oral mucositis in the setting of allogeneic transplantation. The registered primary endpoint focused on severe acute GVHD rather than on all grades of GVHD. Its definition combines grade 3 and grade 4 disease, and assessments were scheduled over the period from transplant through Day 100.

The trial also registered outcomes concerning grade 2 to 4 acute GVHD, severe oral mucositis, duration of severe oral mucositis, opioid analgesic use, hospitalization, mouth and throat soreness, and Day 11 methotrexate GVHD-prophylaxis administration. Those outcomes provide context for the study’s broader aims, but they do not replace the primary question. A registry listing of an outcome does not, by itself, establish the direction or size of a treatment difference.

The record identifies 155 participants as the enrollment and describes randomized allocation, double masking, and a parallel-group model. It does not report the primary outcome counts by assigned treatment in the information available for this analysis. Accordingly, the registered question can be described, but a treatment contrast for the primary endpoint cannot be summarized from the registry record.

3. Trial Design

This was a phase 2, randomized, double-blind, placebo-controlled, parallel-group study sponsored by Swedish Orphan Biovitrum. It enrolled 155 participants and is marked completed. The recorded start was 2005-12, and primary completion was 2008-11. The condition areas were graft-versus-host disease and hematologic malignancies.

Participants were assigned to palifermin or placebo. The palifermin description lists 60 μg/kg daily on 3 consecutive days before the start of conditioning, followed by 180 μg/kg once before transplant and at least 96 hours after the last 60 μg/kg dose. The placebo description follows a corresponding schedule. The registry also lists conditioning regimen, allogeneic stem cell transplant, and methotrexate among the interventions. The detailed arm descriptions are incomplete in the registry record, so additional scheduling or treatment details should not be inferred.

Randomization means treatment assignment was determined through a chance-based process rather than by selecting treatment according to a participant’s characteristics. Double masking indicates that the record describes the trial as double-blind, although it does not specify in the available information exactly which groups of people were masked. A placebo comparator is intended to make the treatment groups more alike in their experience apart from the assigned study treatment. These design features can reduce certain sources of bias, but they do not guarantee that groups remain comparable in every respect or that outcome data are complete.

The primary endpoint was assessed from transplant (Day 0) until Day 100. GVHD grading was scheduled weekly during the first 2 months after stem cell infusion and then every other week until Day 100. The record says analyses were according to randomized treatment assignment in the Primary Analysis Set, described as all randomized participants with GVHD assessments. The precise randomization procedures, masking procedures, allocation ratio, and site details are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary Analysis Set (consisting of all randomized participants) with GVHD assessments. Efficacy analyses were according to randomized treatment assignment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD), measured over From transplant (Day 0) until Day 100.

The primary endpoint was the number of participants with severe, grade 3 or 4, acute GVHD from transplant (Day 0) until Day 100. It counts participants meeting the stated severity definition; it is not a duration measure or a measure of average symptom burden. The registry says severity was determined clinically, using physical examination and laboratory serum values, and from biopsies of affected organs whenever possible. At least 2 assessors scored the degree of GVHD in individual organs.

The listed criteria include grade 3 disease with total bilirubin 3.1 - 15.0 mg/dL, diarrhea of ≥ 1000 mL/day, or severe abdominal pain with or without ileus. Grade 4 includes skin involvement with bullous formation or total bilirubin > 15.0 mg/dL. These definitions make the endpoint clinically categorized rather than a direct continuous measurement. The registry identifies the modified Keystone Criteria as the grading system.

General: A severe-event endpoint can be useful when the study question concerns whether participants experience a defined, serious clinical state during a specified follow-up period. Counting participants makes the outcome straightforward to describe, but interpretation depends on how the event is defined, how consistently it is assessed, and whether participants have sufficient follow-up. This endpoint does not by itself describe the timing, duration, or recurrence of GVHD. The registry record does not provide the primary group counts or a treatment-effect estimate, so the endpoint definition alone cannot establish how the groups compared.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The endpoint counts participants classified as having grade 3 or 4 acute GVHD during the period from transplant (Day 0) until Day 100. It combines two severity grades into one endpoint, while the registry’s grading description distinguishes the clinical criteria for grade 3 from those for grade 4. The outcome is therefore a participant count based on an event classification over a follow-up period. It is not a count of all GVHD, and it is not a measure of how long severe GVHD lasted.

General: A binary outcome records whether a participant experienced an event under a specified definition. This makes it possible to compare event occurrence between treatment groups, but the definition and follow-up window are essential parts of the meaning. Different definitions or observation periods can yield different event classifications. The registry states the grading approach and observation window, but the primary group counts and a summary contrast are not reported in the available record.

What does randomization contribute?

The trial is described as randomized, double-blind, and parallel-group. General: Random assignment is intended to make treatment groups comparable on average with respect to measured and unmeasured participant characteristics. In a well-conducted randomized comparison, this supports interpreting a between-group contrast as an estimate of the effect of assignment, subject to issues such as incomplete outcome collection, departures from assigned treatment, and the analysis choices. Masking can reduce bias in treatment delivery, participant reporting, and outcome assessment, depending on who is masked and how the masking is maintained.

The registry says efficacy analyses followed randomized treatment assignment. That statement indicates an assignment-based approach for efficacy analyses, but does not fully specify the analysis population or the handling of every participant’s outcome. The primary analysis set is described as all randomized participants with GVHD assessments. The detailed randomization process, masking roles, adherence information, and protocol-deviation rules are not reported in the registry record.

How should an effect estimate be read?

General: A treatment-effect estimate summarizes the contrast between groups using a defined scale. For a binary endpoint, common scales include a difference in event proportions or a relative measure, but the appropriate scale depends on the analysis and the question. A confidence interval expresses uncertainty around an estimate under the model and assumptions used. It is not a guarantee that the true effect lies within its limits, and it should be read together with the estimate and the endpoint definition.

No primary effect estimate or confidence interval is reported in the registry record for a single comparison of severe acute GVHD. The record says the primary outcome has several categories or time points and was not reduced to one comparison. It would therefore be inappropriate to reconstruct a treatment effect, p-value, or interval from the endpoint description or from safety counts. The sponsor’s own analysis takes precedence if a recalculated value conflicts with the sponsor’s reported result; no recalculated primary comparison is available in the record.

What can a p-value say?

General: A p-value measures how unusual data at least as incompatible with a specified null model would be, assuming that model and the analysis assumptions. It does not measure the probability that the null hypothesis is true, the probability that a finding is due to chance, or the size or clinical importance of an effect. A p-value also cannot compensate for an unclear endpoint, incomplete reporting, or multiple opportunities to select a favorable analysis.

The registry does not report a primary p-value for a single severe acute GVHD comparison. It also does not report the planned significance threshold, sidedness, test, or model for the primary analysis. These are not inferable from the fact that the study was randomized or from its phase designation.

Why do event timing and follow-up matter?

The primary period runs from transplant (Day 0) until Day 100. The grading schedule is described as weekly during the first 2 months after stem cell infusion and then every other week until Day 100. General: Repeated assessments may help capture events that emerge at different times, but the analysis needs to account for the chosen event definition and follow-up. Participants who do not have complete assessment through the planned period may have uncertain outcome status. The handling of incomplete follow-up can affect the estimate, especially if the chance of missing an assessment is related to health status or treatment assignment.

The registry does not report a time-to-event analysis for the primary endpoint, nor does it report censoring rules or how assessments outside the planned schedule were treated. A count of participants with an event over the period and a time-to-event analysis answer related but distinct questions. The record’s stated primary outcome is a participant count, so a time-to-event interpretation should not be substituted.

What are planning illustrations?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated effect to detect is a specified fraction of the observed effect. These are planning assumptions, not the trial’s original sample-size justification. The registry does not report the trial’s own sample-size justification, and the planning illustrations must not be read as observed power or as evidence that the study had a particular probability of detecting a true effect.

General: Sample-size planning explores how many participants per arm would be needed under chosen assumptions about effect size, variability or event frequency, significance level, and desired power. Changing assumptions changes the planning result. When an observed effect is used as the starting point, the resulting scenarios are conditional illustrations, not independent evidence that the observed effect is real or stable. The numerical planning outputs are not restated.

How should multiple outcomes be considered?

The registry lists 8 outcome measures and 8 analyses. The list includes the primary GVHD outcome and secondary outcomes covering other GVHD grades, oral mucositis, analgesic use, hospitalization, and mouth and throat soreness. General: When many outcomes, time points, subgroups, or analysis choices are examined, the chance of obtaining an apparently notable result somewhere can increase. A prespecified hierarchy or multiplicity adjustment can help control that issue, but the choice depends on the study plan.

The registry record does not report whether a multiplicity strategy was planned or applied, whether the primary outcome was tested at multiple time points, or which secondary outcomes were treated as confirmatory. The fact that the primary outcome was not reduced to one comparison makes it especially important not to select or invent a preferred contrast. Without the analysis plan and the corresponding results, the appropriate interpretation is descriptive and limited to the information registered.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 8 outcome measures and 8 analyses, with the primary endpoint addressing severe acute GVHD and secondary outcomes addressing other GVHD grades, mucositis, analgesic use, hospitalization, and soreness. The primary endpoint is described as involving several categories or time points and was not reduced to one comparison. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or which analyses were intended to be confirmatory.

General: Multiplicity arises when several hypotheses or analysis choices are considered. Even if each test uses a prespecified error threshold, examining many outcomes or time points can increase the chance of at least one apparently notable result. Adjustments, hierarchical testing, or a clear distinction between confirmatory and exploratory analyses can address this, but their use must be documented rather than assumed. The outcome list alone does not establish which approach was used.

The Primary Analysis Set is described as all randomized participants with GVHD assessments, and efficacy analyses were according to randomized treatment assignment. The registry does not explain how participants without an assessment, with incomplete follow-up, or with unclassifiable GVHD status were handled. The number and pattern of missing primary outcome assessments are not reported in the registry record. Nor does the available information specify imputation, sensitivity analyses, or missing-data assumptions.

General: Missing outcome data can weaken a comparison if the participants with recorded outcomes differ systematically from those without them. The direction and size of possible bias depend on why data are missing and on the analysis method. Stating an analysis population does not by itself show that missingness was absent or harmless. The registry’s analysis-population description should therefore be read as limited information about eligibility for analysis, not as proof of complete outcome ascertainment.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: graft versus host disease (21.8%), pyrexia (13.7%), bacteraemia (6.8%), sepsis (6.4%), renal failure acute (6.4%).

The serious adverse event figures list 40 affected participants among 73 at risk in the placebo group and 50 among 78 at risk in the palifermin group. For other adverse events, the corresponding figures are 71 among 73 for placebo and 77 among 78 for palifermin. These are descriptive counts as recorded; they are not the primary efficacy endpoint and should not be interpreted as a causal comparison on their own.

The registry also lists serious adverse event terms with percentages: graft versus host disease, 21.8%; pyrexia, 13.7%; bacteraemia, 6.8%; sepsis, 6.4%; renal failure acute, 6.4%; and nausea, 5.5%. The record does not provide enough detail in the available information to define the denominator for each listed term or to explain whether a participant could contribute to multiple terms. Those percentages should be read as registry-listed values, not as mutually exclusive categories.

The death counts are not reported in the registry record. The available safety information does not describe event severity criteria, exposure duration, event timing, relatedness assessments, or a statistical comparison between groups. General: Safety counts are useful for describing events recorded during a trial, but their interpretation depends on definitions, follow-up, exposure, and reporting practices. The figures do not by themselves establish that a treatment caused an event or that the groups differed reliably.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a randomized, double-blind, placebo-controlled phase 2 study evaluated palifermin in people with hematologic malignancies undergoing allogeneic transplantation. It defines the primary outcome as the number of participants with grade 3 or 4 acute GVHD from transplant (Day 0) until Day 100 and describes the grading criteria and assessment schedule. These details clarify the intended question and the clinical event being counted.

The record does not provide a single primary-outcome comparison. It says the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the registered information available for this analysis cannot establish whether the palifermin group had more or fewer primary events, how large any treatment contrast was, or how precisely such a contrast was estimated. No conclusion about treatment efficacy should be drawn from the endpoint definition alone.

The adverse event counts and listed serious adverse event terms describe safety information recorded in the registry. They do not substitute for primary efficacy results, and they do not show that an event was caused by the assigned treatment. A valid safety comparison would require clear event definitions, exposure and follow-up context, and an appropriate analysis. The registry information does not provide all of those details.

General: A randomized trial estimates effects for the population, treatment setting, outcome definitions, and follow-up actually studied. Even when a result is reported, it does not automatically establish effects in different populations or settings. In this case, the missing primary comparison means the record supports a description of the study question and design, but not a conclusion about the direction, size, or certainty of the primary treatment effect. The registry record also does not report the full statistical analysis plan or the trial’s own sample-size justification.

The registered secondary outcomes may be relevant to the study’s broader objectives, particularly oral mucositis and other transplant-related outcomes. However, listing an outcome is not evidence of a result, and the information available does not establish how those outcomes compared between groups. The most defensible reading is therefore bounded: the trial was designed to investigate the stated clinical question, but the registry record does not offer a single interpretable primary result in the information described.

13. Why This Trial Matters Statistically

This trial is statistically notable because its design and primary endpoint are identifiable, while the primary comparison is not presented as one result in the registry record. That distinction is important for evidence interpretation. Knowing the endpoint definition and follow-up period does not reveal the treatment effect; a transparent comparison requires group outcome data and an estimate with uncertainty, or an equivalent clearly specified analysis.

The endpoint also illustrates how clinical outcomes depend on operational definitions. Severe acute GVHD was defined through grade 3 or 4 classifications under modified Keystone Criteria, with assessment based on clinical findings, laboratory values, and biopsies when possible. The timing of assessments and the use of multiple assessors are part of how the outcome was meant to be measured. If definitions or assessment practices differ, event counts may not be directly comparable across studies.

Randomization and masking are meaningful design features, but they do not resolve reporting gaps. A reader still needs to know how missing assessments were handled, which comparisons were prespecified, and what estimates were obtained. This record identifies an analysis population and assignment-based efficacy analyses, but does not supply the details needed to assess these questions fully.

The registry also records multiple outcomes, including GVHD, mucositis, analgesic use, hospitalization, and mouth and throat soreness. This breadth makes clear why prespecification and multiplicity handling matter: readers need to distinguish a primary confirmatory question from secondary or exploratory analyses. The record does not provide that distinction in sufficient detail.

The statistical lesson is not that the trial found a particular result, but that conclusions must track the information actually reported. Design labels, outcome definitions, safety counts, and planning assumptions each answer different questions. None can stand in for an unreported primary treatment-effect estimate.

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 central limitation for interpreting efficacy is that the registry record does not give a single primary comparison for severe acute GVHD. It explicitly notes that the primary outcome has several categories or time points and was not reduced to one comparison. Without group-specific primary outcome results and an estimate of uncertainty, the direction, magnitude, and precision of the treatment contrast cannot be evaluated.

The registry’s account of the analysis is incomplete. It identifies all randomized participants with GVHD assessments as the Primary Analysis Set and states that efficacy analyses followed randomized treatment assignment. It does not report how missing assessments, incomplete follow-up, protocol deviations, or unclassifiable outcomes were handled. The detailed statistical plan, model or test, confidence intervals, and primary p-value are not reported in the registry record.

The record lists several outcome measures but does not explain a testing hierarchy or multiplicity strategy. It is also unclear from the available information which time points or categories were included in each analysis. No subgroup analysis plan or results are described. These omissions limit the ability to distinguish prespecified inference from exploratory examination.

The arm descriptions are truncated, and the registry does not fully detail treatment delivery, adherence, or all concurrent-care procedures. Although methotrexate is listed as an intervention and Day 11 administration is a registered secondary outcome, the available information does not establish the full prophylaxis regimen or how administration patterns were handled analytically.

Safety figures are descriptive and lack some contextual details, including event timing, exposure duration, and the definition of each safety category. Death counts are not reported in the registry record. The record also does not provide the trial’s own sample-size justification. Planning illustrations based on an observed effect cannot fill that gap or serve as evidence of observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation — NCT00189488.
• Registry record last updated 2014-09-15; status last verified 2014-09.
• Results first posted 2014-09-15.
• 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.

18. Record Summary

NCT00189488 is a completed randomized, double-blind, placebo-controlled phase 2 trial sponsored by Swedish Orphan Biovitrum. The parallel-group study enrolled 155 participants with hematologic malignancies undergoing allogeneic marrow or peripheral blood progenitor cell transplantation. The recorded start was 2005-12 and primary completion was 2008-11.

The primary outcome was the number of participants with grade 3 or 4 acute GVHD from transplant (Day 0) until Day 100. The registry describes the modified Keystone Criteria and the assessment schedule, but does not provide a single primary comparison. It identifies a Primary Analysis Set of randomized participants with GVHD assessments and says efficacy analyses followed randomized assignment.

Registered secondary outcomes address other GVHD grades, oral mucositis, opioid analgesic use, hospitalization, soreness, and methotrexate administration. Safety counts and selected serious adverse event terms are also recorded. The statistical plan, missing-data handling, multiplicity approach, and the trial’s own sample-size justification are not reported in the registry record.