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 R-ICE and High-Dose Cyclophosphamide With PET/CT for Diffuse Large B-Cell Non-Hodgkin's Lymphoma (NCT00809341), a non-randomized phase 2 study. The primary outcome is Event-free Survival in Patient Receiving Early Treatment Intensification Based on a Positive Mid-treatment PET Scan.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00809341 |
| Phase | Phase 2 |
| Condition | Non-Hodgkin's Lymphoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 27 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with non-Hodgkin lymphoma. Its summary describes newly diagnosed lymphoma treated initially with R-CHOP or an equivalent anthracycline-containing regimen. The registry record does not report further eligibility details such as age or disease characteristics.
Intervention
Participants were to receive an early PET scan after 3 cycles of initial chemotherapy. Those with a positive scan were assigned to an intensification pathway: two cycles of R-ICE followed by high-dose cyclophosphamide. The registry record does not give further details of the high-dose cyclophosphamide regimen.
Comparator
Participants with a negative PET scan were to complete chemotherapy as prescribed by their oncologist. This was not a randomized comparison: the pathways were determined by PET result, so the groups were not designed as like-for-like controls.
Primary question
The stated primary outcome was event-free survival among patients receiving early treatment intensification based on a positive mid-treatment PET scan, with a 2 years timeframe. The study aimed to evaluate PET-guided treatment decisions, but the outcome data were not collected because a standardized PET evaluation mechanism was not established. The record therefore does not answer whether the strategy changed event-free survival.
3. Trial Design
NCT00809341 was a phase 2, parallel, non-randomized study with no masking. The registry lists enrollment of 27 and identifies Non-Hodgkin's Lymphoma as the condition. The recorded start was 2009-01 and primary completion was 2014-04. Its status is terminated.
The treatment strategy began with R-CHOP or an equivalent anthracycline-containing regimen for 3 cycles, followed by a PET scan. Participants with a negative scan were to continue their chemotherapy regimen as prescribed by their oncologist. Participants with a positive scan were to receive two cycles of R-ICE followed by high-dose cyclophosphamide. The pathways therefore depended on PET status rather than random allocation.
The distinction matters for interpretation. A comparison between PET-negative and PET-positive participants would combine differences in scan status with differences in treatment pathway. It would not isolate the effect of intensification as a randomized treatment comparison. The registry record also states that the study was placed on hold while a quantitative method for evaluating PET scans was considered. No decision was reached on that mechanism, and the study was terminated.
The record does not report a statistical analysis plan, a sample-size justification, or details of allocation procedures beyond the non-randomized designation. It lists two outcome measures and zero analyses. The primary outcome data were not collected because a standardized PET evaluation mechanism was not available. Thus, the study design describes an intended clinical strategy, but the registry does not contain the planned primary-outcome comparison.
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.
Before assignment: 1 participant was deemed ineligible and therefore not assigned to intervention. One participant withdrew informed consent prior to starting the study.
Overall Study
| Stage | PET Negative | PET Positive |
|---|---|---|
| STARTED | 20 | 5 |
| COMPLETED | 20 | 4 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | PET Negative | PET Positive |
|---|---|---|
| Physician Decision | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The study was placed on hold to determine a quantitative method for the evaluation of PET scan results. No decision was reached on the evaluation mechanism for the PET scans, so the study was terminated. Data for this outcome was not collected because a standardized evaluation mechanism for the PET scans was not found.
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 | PET Negative | PET Positive | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 5 | 25 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 | 4 | 19 |
| Age, Categorical: >=65 years | Participants | 5 | 1 | 6 |
| Age, Continuous | years | 52.5 (23 to 72) | 50 (26 to 66) | 52 (23 to 72) |
| Sex: Female, Male: Female | Participants | 8 | 1 | 9 |
| Sex: Female, Male: Male | Participants | 12 | 4 | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Event-free Survival in Patient Receiving Early Treatment Intensification Based on a Positive Mid-treatment PET Scan, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was event-free survival for patients receiving early treatment intensification based on a positive mid-treatment PET scan, with a 2 years timeframe. The registry record does not define which events counted toward event-free survival, nor does it specify the endpoint's unit, parameter, or dispersion. Those details are not reported in the registry record.
In general, event-free survival is a time-to-event measure: it describes how long participants remain without an event defined by the study. It can represent both whether an event occurs and when it occurs. The precise event definition is essential, because different event rules can produce different endpoint results. The registry record does not specify its event definition, so the endpoint cannot be interpreted more narrowly than its stated name.
In general, time-to-event analyses can use information from participants who have not experienced the event by the end of observation, provided their follow-up and censoring are handled appropriately. The registry record does not describe follow-up completeness, censoring rules, or any analysis method for this endpoint. Most importantly, the primary outcome data were not collected. There is therefore no reported event-free survival estimate or uncertainty interval to interpret.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical finding is the absence of a primary efficacy result. The registry names event-free survival as the primary outcome and gives a 2 years timeframe, but also states that the data were not collected. The study was held while investigators sought a quantitative PET evaluation method; no decision was reached, and the study was terminated. Without the outcome data, the posted results cannot estimate event-free survival or quantify how precisely it was measured.
The study enrolled 27, but the registry does not provide a primary-outcome analysis. It lists zero analyses. The adverse-event summary reports PET Negative and PET Positive groups, but those descriptive safety counts do not substitute for the missing efficacy endpoint. The record does not explain how the adverse-event group counts relate to the enrollment figure, and no reconciliation is reported.
The design also limits any interpretation of differences between the PET-defined pathways. PET status determined which treatment participants received, and allocation was non-randomized. A difference between such groups could reflect differences associated with PET status as well as treatment, rather than an isolated treatment effect. The registry itself flags that the arms are not a like-for-like control comparison. No causal effect of intensification can be established from a direct contrast of these groups.
Secondary outcomes include overall survival in patients whose treatment was determined on the basis of a mid-treatment PET scan. The registry provides no analysis of that outcome either. It does not report estimates, confidence intervals, hypothesis tests, or adjusted comparisons for the stated outcomes. Consequently, there is no basis in the registry record for judging the direction, size, or precision of an efficacy association.
Safety information is descriptive and should be read separately. Serious events are recorded in both PET-defined groups, and deaths are listed by group, but the record does not provide the context needed to interpret comparative risk, such as a defined observation period or a statistical comparison. These counts describe what the record lists; they do not establish that one pathway caused more or fewer events.
Overall, the posted information documents an intended PET-guided strategy and a reason the study ended without its primary endpoint data. It does not provide evidence for or against a treatment effect on event-free survival. The absence of an estimate is not evidence of no effect; it means the stated endpoint could not be evaluated from the collected study data.
9. Statistical Methods Explained
The registry describes a phase 2, parallel study with non-randomized allocation and no masking. These design labels set limits on the conclusions that a statistical analysis could support. The reported outcomes include event-free survival as the primary endpoint and overall survival as a secondary outcome. However, the registry lists zero analyses, and the primary outcome data were not collected. The methods that would have been used to estimate treatment effects are not reported in the registry record.
What does non-randomized allocation mean?
In general, random allocation helps make treatment groups comparable with respect to measured and unmeasured characteristics at the point of assignment. In a non-randomized study, treatment assignment may be linked to participant characteristics or clinical measurements. In this trial, the PET result determined the treatment pathway: PET-positive participants were to receive intensification, while PET-negative participants were to continue their prescribed chemotherapy. PET status therefore defines the groups and is not simply a randomized treatment assignment.
This distinction matters when interpreting comparisons. A contrast between the pathways cannot be read as the effect of intensification alone, because the groups differ by the scan result that triggered treatment. Statistical adjustment can sometimes address measured differences, but the record does not report an adjustment plan or analyses, and adjustment cannot guarantee removal of unmeasured differences. The registry flags the arms as not a like-for-like control comparison.
What would an event-free survival analysis describe?
In general, time-to-event methods use information about the timing of events rather than reducing each participant's experience to a simple event/no-event indicator. They can incorporate participants whose follow-up ends before an event is observed, using censoring rules. The validity of such methods depends on clear definitions of the event, the observation period, and follow-up. For this study, the registry states a 2 years timeframe but does not define the events, report censoring rules, or describe a model or estimator. Because data for the primary outcome were not collected, no event-free survival curve, estimate, or uncertainty interval is reported.
A confidence interval, in general, expresses the statistical uncertainty around an estimate under the assumptions of the analysis. Its width depends on factors such as the amount of information available and the variability of the outcome. A confidence interval is not a guarantee that a particular value is correct. No confidence interval for the primary endpoint is available in the registry record, so its precision cannot be assessed.
How should the PET-defined groups be understood?
The PET scan was intended to guide a treatment decision after the initial chemotherapy. This makes the trial a study of a strategy based on an early measurement, not a randomized test in which otherwise comparable participants were assigned to intensification or continuation. A positive scan can be associated with prognosis, and the treatment pathway followed the scan result. In general, this means that differences in later outcomes could reflect scan-defined risk, treatment, or both. The registry does not report data or analyses that separate these explanations.
The study was placed on hold because a quantitative method for evaluating PET results was being considered. A consistent scan classification process is important in a strategy study: if the method used to determine a positive or negative result is not standardized, the basis for assigning treatment may be unclear or vary across assessments. The record says no decision was reached on an evaluation mechanism. It does not report a final PET scoring method, reader procedures, or a plan for resolving differences in interpretation.
What do the planning assumptions mean?
The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. For time-to-event calculations, the illustration is based on the total number of events; other calculations are expressed as participants per arm. These are planning assumptions, not a description of the trial's own design or a report of observed power.
The primary outcome data were not collected, and the registry record does not report an observed event-free survival effect to interpret. Any planning illustration should therefore not be treated as evidence that the study had a particular probability of detecting a treatment effect. In general, sample-size calculations depend on assumptions about the effect, variability, allocation, and analysis. A planning calculation can explore hypothetical requirements under stated assumptions; it cannot replace collected outcome data or establish what the study actually detected.
No statistical analysis plan, interim-analysis procedure, multiplicity adjustment, missing-data method, or analysis population is reported in the registry record. It is therefore not possible to assess whether a particular modeling approach, adjustment strategy, or sensitivity analysis was planned or used. The available methods information supports a limited conclusion: the intended comparison depended on PET-guided pathways, but the primary endpoint was not collected and no outcome analysis is reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary event-free survival outcome and a secondary overall survival outcome. It reports zero analyses. The primary event-free survival data were not collected because a standardized evaluation mechanism for PET scans was not established. The registry does not report whether overall survival data were collected or analyzed, and no estimate for that secondary outcome is posted.
When a study examines multiple outcomes or multiple statistical comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control or describe that issue, but the appropriate approach depends on the planned analyses and their priority. The registry record does not report a multiplicity strategy, a hierarchy of tests beyond identifying primary and secondary outcomes, or any hypothesis-test results. No adjusted or unadjusted efficacy result is available to interpret.
The record also does not report an analysis population, participant-level follow-up, missing-data handling, censoring rules, or reasons for any missing observations beyond the lack of collected primary outcome data. The sample-size assumptions do not supply a missing analysis plan. Without those details, readers cannot determine how outcome availability would have been handled had data existed, or whether analysis populations were intended to differ by endpoint.
These omissions should not be filled by assumptions about common trial practice. The registry does not describe interim analyses, imputation, sensitivity analyses, or a statistical plan. The clearest limitation is that the primary endpoint was not collected, while the record provides no analysis of either listed outcome.
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 |
|---|---|---|---|
| PET Negative | 0 | 20 | 0.0% |
| PET Positive | 3 | 5 | 60.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PET Negative | 1 of 20 |
| PET Positive | 0 of 5 |
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 |
|---|---|
| PET Negative | 0 of 20 |
| PET Positive | 0 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | PET Negative | PET Positive |
|---|---|---|---|
| Febrile Neutropenia | Infections and infestations | 0 of 20 | 2 of 5 |
| Hemorrhage, CNS | Nervous system disorders | 0 of 20 | 1 of 5 |
Serious events with the highest arm-level rate: febrile neutropenia (40.0%), hemorrhage, cns (20.0%).
The registry reports serious adverse-event group counts for PET Negative and PET Positive participants. In the PET Negative group, 0 of 20 were recorded as having a serious adverse event and 0 of 20 as having another adverse event; the record lists 1 death. In the PET Positive group, 3 of 5 were recorded as having a serious adverse event and 0 of 5 as having another adverse event; the record lists 0 deaths. These are the registry's counts, not a randomized comparison.
The registry also lists Febrile Neutropenia at 40.0% and Hemorrhage, CNS at 20.0% among the top serious terms. It does not specify the denominator or provide further context for those percentages in the posted summary, so they should not be assigned to a particular group or interpreted as comparative rates.
The record does not state the adverse-event observation period, the event definitions, or whether the counts refer to unique participants or event occurrences. Counts alone do not show how risk varied over time, and they do not establish that treatment caused an event. Because the groups were defined by PET result and were not randomized, differences in their counts should not be interpreted as treatment effects. The safety information is descriptive; the registry does not report a statistical comparison or uncertainty intervals for these figures.
12. What the Result Does, and Does Not, Mean
The record documents a planned use of mid-treatment PET to guide therapy for non-Hodgkin lymphoma. After 3 cycles of initial chemotherapy, PET-negative participants were to continue their prescribed regimen, while PET-positive participants were to receive R-ICE followed by high-dose cyclophosphamide. The primary question concerned event-free survival in patients receiving early intensification based on a positive PET scan.
What the record does establish is that the study was phase 2, non-randomized, and terminated. It gives enrollment of 27 and reports that the primary outcome data were not collected. The stated reason was that the study was placed on hold to determine a quantitative method for evaluating PET results; no decision was reached on the evaluation mechanism. The registry lists two outcome measures but no analyses.
What the record does not establish is whether PET-guided intensification changed event-free survival or overall survival. There is no reported estimate, confidence interval, or statistical test for either outcome. No result should be inferred from the fact that the study ended, from the listed adverse-event counts, or from the planned treatment strategy. In particular, the missing primary endpoint is not evidence that the strategy had no effect.
The registry also cannot support a causal contrast between PET-positive and PET-negative pathways. Scan status determined the pathway, so group membership was not randomized. Those groups are not like-for-like controls; a difference in outcome, if it had been reported, could reflect PET status as well as treatment. The record does not report an analysis designed to address that issue.
Thus, the statistical meaning is primarily about what could not be estimated. The trial recorded a clinical strategy and descriptive safety information, but its posted results do not answer its primary outcome question. The study's status and missing endpoint data should be kept distinct from any claim about treatment benefit or harm.
13. Why This Trial Matters Statistically
This trial is statistically informative because it illustrates how a clinical strategy can depend on a measurement process that must be defined consistently. PET results were intended to determine whether participants continued their prescribed chemotherapy or received early intensification. The registry reports that the study was held while a quantitative PET evaluation method was considered, but no decision was reached. Without a standardized evaluation mechanism, the proposed treatment rule could not be operationalized as intended.
The case also highlights the difference between a treatment comparison and a strategy comparison. Because the treatment pathways were assigned according to PET status, the groups were not randomized controls for one another. Statistical interpretation would need to distinguish the prognostic information in the scan from any effect of the subsequent treatment. The registry's own note that the arms are not a like-for-like control comparison is therefore central, not a minor design detail.
Finally, a named primary endpoint is not the same as a measured endpoint. Event-free survival was specified with a 2 years timeframe, but the record states that its data were not collected. No estimate or precision measure can be recovered from a planned endpoint alone. The trial therefore demonstrates why a clearly specified and consistently applied measurement procedure is part of the statistical design, and why the absence of outcome data must not be interpreted as a null result.
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 consequential limitation is explicit: the primary event-free survival outcome was not collected. The registry attributes this to the lack of a standardized PET evaluation mechanism after the study was placed on hold. No decision was reached about how PET scans would be evaluated, and the study was terminated. As a result, the intended primary question cannot be answered from the posted results.
The endpoint description is also incomplete. The record names event-free survival, gives a 2 years timeframe, and does not define the events included. It does not report the analysis method, censoring rules, follow-up completeness, or an estimate with its precision. Details of the overall survival outcome are also limited to its title; no analysis is reported.
The non-randomized, PET-defined pathways constrain interpretation of any group contrast. PET-positive and PET-negative participants were not like-for-like controls, because the scan result determined treatment. The registry does not report an adjustment strategy that might address measured differences, and no analysis is posted. Enrollment is listed as 27, while adverse-event summaries identify group-specific risk counts; the record does not explain the relationship between these counts and enrollment.
Additional limitations include the absence of a reported statistical analysis plan, sample-size justification, analysis population, missing-data approach, or multiplicity strategy. The adverse-event summary lacks an observation period and contextual detail for the top serious terms. These limitations are specific to the available registry record; further details are not reported in the registry record and should not be assumed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: R-ICE and High-Dose Cyclophosphamide With PET/CT for Diffuse Large B-Cell Non-Hodgkin's Lymphoma — NCT00809341.
- Registry record last updated 2018-09-25; status last verified 2018-09.
- Results first posted 2018-09-25.
- 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
NCT00809341 was a phase 2, parallel, non-randomized study with no masking, listed for Non-Hodgkin's Lymphoma. The registry reports enrollment of 27, a start of 2009-01, primary completion of 2014-04, and terminated status.
The intended strategy used a PET scan after 3 cycles of initial chemotherapy to guide subsequent treatment. PET-positive participants were to receive R-ICE followed by high-dose cyclophosphamide; PET-negative participants were to complete chemotherapy as prescribed by their oncologist. The primary outcome was event-free survival for patients receiving early intensification based on a positive mid-treatment PET scan, with a 2 years timeframe.
The study was held to determine a quantitative PET evaluation method, no decision was reached, and primary outcome data were not collected. The registry lists two outcome measures and zero analyses. Consequently, it reports no primary efficacy estimate and does not answer the stated event-free survival question.