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 DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma (NCT02815397), a na phase 2 study. The primary outcome is Evaluation of Impact of Metformin on 18 Month Progression-free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02815397 |
| Phase | Phase 2 |
| Condition | Diffuse Large B-Cell Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Rush University Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
People with newly diagnosed, histologically confirmed, previously untreated c-myc+ de novo diffuse large B-cell lymphoma. The registry does not report further eligibility details in the record described.
Intervention
Metformin added to standard induction therapy with DA-EPOCH-R. The listed regimen begins with 500 mg daily x 1 week, followed by 500 mg twice daily x 2 weeks, then 850 mg twice daily until 1 month after the last cycle of chemo-immunotherapy.
Comparator
There was no concurrent control group. The registry describes a single-group, open-label study in which metformin was added to standard care for all participants.
Primary question
The primary endpoint was the impact of metformin on progression-free survival at 18 months, assessed by CT scans. The registry states that this outcome data would not be available because the study closed prematurely, so the primary question cannot be answered from the posted results.
3. Trial Design
This was a phase II, single-group, open-label study sponsored by Rush University Medical Center. Its title identifies DA-EPOCH-Rituximab/Metformin for Double Hit Lymphoma, while the official title describes evaluation of metformin with standard induction therapy for previously untreated c-myc+ diffuse large B-cell lymphoma. The registry lists the condition as diffuse large B-cell lymphoma.
Metformin was added to DA-EPOCH-R. The listed metformin schedule was 500 mg daily x 1 week, then 500 mg twice daily (BID) x 2 weeks, followed by 850 mg twice daily until 1 month after the last cycle of chemo-immunotherapy. DA-EPOCH-R was planned every 21 days x 4 cycles. Intrathecal CNS prophylaxis, as single or triple therapy, was to be given each cycle to patients considered appropriate by the treating physician.
After 4 cycles, participants were to be restaged with CT. For complete remission or partial remission, the described plan allowed 2 more cycles or radiation therapy (XRT) consolidation per physician. Stable or progressive disease was to lead to salvage therapy off study. These are the registry's described treatment plans; the record does not establish how far each participant proceeded through them.
Allocation is listed as NA, masking as none, and the model as single group. The registry lists enrollment as 2, a start date of 2016-02, primary completion in 2016-07, and status as terminated. The reason for termination is not reported in the registry record. A concurrent standard-care group was not included, so outcomes cannot be compared directly with an untreated or alternative-treatment group.
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 | Single Arm, Open Label |
|---|---|
| STARTED | 2 |
| COMPLETED | 0 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Single Arm, Open Label |
|---|---|
| Physician Decision | 2 |
Analysis population for the primary outcome, as defined in the registry: will not have this data as study closed prematurely.
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 | Single Arm, Open Label |
|---|---|---|
| Participants analysed | 2 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Evaluation of Impact of Metformin on 18 Month Progression-free Survival, measured over 18 month.
| 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 the impact of metformin on progression-free survival at 18 months. The registry describes progression-free survival as determined by CT scans at 18 months. In general, progression-free survival refers to the time patients remain alive without disease progression; however, the registry record does not give a more detailed operational definition, event-adjudication procedure, or rules for censoring.
A time-to-event endpoint can describe both whether and when an event occurs, rather than only recording a status at a single visit. Assessing progression-free survival is therefore a way to evaluate disease control over a defined follow-up period. The registry's stated assessment was tied to CT scans at 18 months, but it does not report a schedule of additional scans or explain how scans and clinical events were combined in endpoint determination.
Most importantly, the registry explicitly states that the 18-month progression-free survival data would not be available because the study closed prematurely. No primary endpoint estimate, confidence interval, or analysis is reported in the registry record. The endpoint's intended meaning can be described, but the posted results do not establish an outcome for this question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a phase II study of metformin added to DA-EPOCH-R, but does not report an estimate for its primary endpoint. The intended endpoint was progression-free survival at 18 months, determined by CT scans. The record says that this data would not be available because the study closed prematurely. Consequently, there is no posted primary result from which to assess the observed progression-free survival or the precision of an estimate.
The record lists enrollment as 2. This is important context for interpreting the status of the study, but it does not substitute for outcome data. The registry does not report how many participants completed treatment, were assessed at the endpoint, or contributed to any endpoint analysis. It also does not report a primary analysis or any analyses in the listed analysis count. It would be inappropriate to infer a response, progression-free survival estimate, or treatment effect from the enrollment listing alone.
The study had a single group and no concurrent comparator. Even if endpoint results had been reported, a single-group result would describe the observed outcomes in the treated group rather than estimate a randomized contrast against another treatment. Differences between groups cannot be separated from differences in participant characteristics, care, follow-up, or other influences when there is no concurrent comparison arm.
Secondary outcomes listed in the registry include overall response rate, overall survival, and safety as assessed by the number of participants with treatment-related adverse events using CTCAE v.4.0. The posted record does not give interpretable outcome estimates for these questions. The adverse-event entry lists zeros for participants at risk, affected participants, and deaths; these entries do not establish that no adverse events occurred, because the record also does not provide a usable exposure or analysis denominator and the study's outcome data are incomplete.
The registry's status is terminated, but the reason is not reported in the registry record. Neither the status nor the absence of posted results indicates why the study ended. The appropriate statistical conclusion is limited: the study was planned to assess metformin in a single group, but the registry record does not contain the primary endpoint data needed to evaluate that question. No treatment-benefit or treatment-harm conclusion follows from these missing results.
9. Statistical Methods Explained
The registry identifies this as a phase II, single-group study with no masking. Allocation is recorded as NA, consistent with the stated design that all participants in the single arm received metformin added to standard care. Since there is no randomized comparison, a between-group treatment effect cannot be estimated from this design. Any outcome estimate, if available, would describe the treated group; it would not by itself show what would have occurred under another treatment.
What does progression-free survival measure?
In general, progression-free survival is a time-to-event outcome that tracks how long participants remain alive without disease progression. A time-to-event analysis can account for differing follow-up times and can use information from participants whose event status is not known through the full follow-up period, if the analysis plan specifies suitable censoring rules. Those rules matter: the handling of deaths, missed assessments, withdrawal, and other incomplete follow-up can affect the estimate. The registry describes the primary endpoint as progression-free survival determined by CT scans at 18 months, but detailed event definitions and censoring methods are not reported in the registry record.
For the planned endpoint to be estimated, the analysis would need endpoint observations and a clear account of follow-up. The registry states that the 18-month data would not be available because the study closed prematurely. It does not give an estimate, interval, test, or number of participants assessed at that endpoint. Accordingly, general descriptions of time-to-event methods should not be mistaken for methods documented as having been used in this study.
What can a confidence interval tell readers?
In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, while an interval that spans a broad range of plausible values signals substantial uncertainty. A confidence interval does not correct for bias, missing observations, or the lack of a comparator. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.
What is the role of the planning illustrations?
The planning assumptions describe illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They distinguish time-to-event planning in terms of total events from other planning in terms of participants per arm, and describe effects as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study used a two-arm design. The actual study is listed as single group, and the primary observed effect is not reported. Planning sample sizes are hypothetical design illustrations; they are not observed power and cannot fill the gap left by absent endpoint results.
In general, over-dispersion means that variability in count data exceeds what a simple model assumes. If a count outcome has over-dispersion, standard errors and uncertainty estimates from a model that ignores it may be too small. No count-model analysis or assessment of over-dispersion is reported in the registry record, and this issue does not supply an alternative analysis of the missing primary endpoint.
What analyses are documented?
The registry lists zero analyses. It does not report whether the primary analysis was intended to be intention-to-treat, per-protocol, or based on another analysis population. It also does not report a model for the primary endpoint, a statistical test, an adjustment strategy, or any interim analysis plan. These details should not be inferred from the phase or study title. Without the endpoint observations and an analysis description, neither effect magnitude nor statistical uncertainty can be reconstructed from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: the primary endpoint of 18-month progression-free survival, plus secondary outcomes for overall response rate, overall survival, and treatment-related adverse events assessed using CTCAE v.4.0. It does not report how these outcomes were prioritized for statistical testing beyond identifying the primary endpoint, or whether any adjustment for multiple comparisons was planned. The number of analyses listed is zero. A formal multiplicity strategy is therefore not reported in the registry record.
In general, testing several outcomes can raise the chance of observing a nominally unusual result by chance when each is treated as a separate confirmatory test. Multiplicity procedures can address this issue, but their selection depends on the planned hypotheses and analysis strategy. Since there are no posted outcome estimates or inferential analyses, no correction or hierarchy can be evaluated.
The record says the primary endpoint data would not be available because the study closed prematurely. It does not describe the amount or pattern of missing endpoint data, reasons for missing observations, follow-up completeness, or any imputation or sensitivity analyses. Nor does it specify an analysis population or state which participants contributed to each endpoint. These omissions make it impossible to assess whether missingness could have affected an estimate.
In general, missing-data methods rely on assumptions about why values are unavailable; different assumptions can lead to different conclusions. A registry statement that data would not be available is not itself a missing-data analysis. The posted record offers no basis to determine how incomplete follow-up was handled, or whether it was handled analytically at all.
11. What the Result Does, and Does Not, Mean
The record establishes the study's intended question and design: metformin was added to DA-EPOCH-R in a single-group, open-label phase II study, with 18-month progression-free survival as the primary endpoint. It also reports that the study was terminated and that the primary endpoint data would not be available because the study closed prematurely. These registry entries describe the trial and its reporting status; they do not answer whether the regimen changed progression-free survival.
The registry lists enrollment as 2, but does not report participant-level outcomes or an endpoint estimate. Without those results, readers cannot determine the observed outcome, how precisely it was estimated, or whether the secondary outcomes differed from any benchmark. The absence of a concurrent control group would also limit causal interpretation even if a single-group outcome estimate were available.
The adverse-event record contains zero values for participants at risk, affected participants, and deaths. Those entries should not be read as proof that no adverse events occurred. The record does not report a usable denominator, event narratives, exposure duration, or a safety analysis. The intended safety assessment—treatment-related adverse events using CTCAE v.4.0—does not replace the missing outcome information.
In general, a nonsignificant test would not establish equivalence or absence of an effect, and a missing test cannot be interpreted as a negative result. Here, the registry does not report an endpoint test or estimate at all. The appropriate conclusion is that the posted information is insufficient to quantify efficacy or safety outcomes, not that the treatment did or did not have an effect.
The terminated status alone does not explain why the study ended. The reason for termination, and any relationship between termination and outcomes, is not reported in the registry record. Conclusions about the study's conduct or the reasons results are unavailable would therefore go beyond the documented information.
12. Why This Trial Matters Statistically
This trial illustrates a fundamental distinction in clinical-trial statistics: a clearly stated research question is not the same as an answer supported by outcome data. The registry identifies a primary endpoint and a treatment plan, but explicitly says the 18-month progression-free survival data would not be available because the study closed prematurely. Without an endpoint estimate, readers cannot evaluate effect magnitude or precision.
The single-group structure also matters. A treated-group outcome can describe what was observed among participants with available data, but a concurrent comparator is needed to make a direct between-group contrast. In its absence, causal interpretation is more limited because outcomes may reflect factors other than the intervention. In this record, even a treated-group primary estimate is not reported.
The registry lists enrollment as 2. That context highlights why outcome completeness and analysis populations are important to report, but the record does not provide the follow-up details needed to understand what information was collected. The planned secondary outcomes likewise cannot be assessed from the posted results.
The example also shows why absence of a reported result should not be translated into a finding of no effect or no harm. Statistical conclusions require data, an analysis, and uncertainty measures. The registry's termination status and incomplete outcome record leave the primary clinical question unresolved, while the reason for termination is not reported. Clear distinction between what was planned, what was recorded, and what can be inferred is essential for responsible interpretation.
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 main trial-specific limitation is the missing primary endpoint result. The registry states that 18-month progression-free survival data would not be available because the study closed prematurely. No endpoint estimate, confidence interval, or analysis is reported, so neither outcome magnitude nor precision can be assessed.
The single-group design provides no concurrent comparator. The registry therefore cannot support a direct comparison between metformin plus DA-EPOCH-R and another treatment strategy. The study is listed as open-label, with no masking, which may also be relevant to how assessments and care were conducted; the record does not report procedures designed to limit assessment bias.
The record lists enrollment as 2, but does not report how many participants completed the planned regimen, had endpoint assessments, or were included in any outcome analysis. It also does not describe follow-up completeness or missing-data handling. The reason for termination is not reported in the registry record, so the implications of the early closure cannot be determined from the available description.
Although overall response rate, overall survival, and treatment-related adverse events were listed as secondary outcomes, the record does not give interpretable results for them. The adverse-event listing's zero entries do not establish the absence of events in the absence of a usable denominator and detailed safety data. The statistical analysis plan, analysis populations, and multiplicity handling are also not reported in the registry record.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma — NCT02815397.
- Registry record last updated 2017-11-17; status last verified 2016-12.
- Results first posted 2017-11-17.
- 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
NCT02815397 is a phase II, single-group, open-label study of metformin added to DA-EPOCH-R for previously untreated c-myc+ diffuse large B-cell lymphoma. The registry lists Rush University Medical Center as sponsor, enrollment as 2, a start date of 2016-02, primary completion in 2016-07, and status as terminated.
The primary outcome was progression-free survival at 18 months, determined by CT scans. The registry states that this data would not be available because the study closed prematurely. Secondary outcomes included overall response rate, overall survival, and treatment-related adverse events assessed using CTCAE v.4.0, but interpretable results are not reported. The reason for termination, detailed analysis methods, and handling of missing data are not reported in the registry record.