This page separates reported trial information from statistical interpretation. The ClinicalTrials.gov record identifies one registered binary primary endpoint and two posted statistical analyses for secondary endpoints. Numerical results are reported only where the ClinicalTrials.gov record provides an estimate, confidence interval, or P-value.
1. Trial at a Glance
R-CVP was a randomized, parallel-group, open-label phase 3 study evaluating bendamustine and rituximab against R-CHOP/R-CVP in the first-line treatment of patients with advanced indolent non-Hodgkin's lymphoma or mantle cell lymphoma.
| Feature | R-CVP |
|---|---|
| Trial name | R-CVP |
| Phase | Phase 3 |
| Status | Completed |
| Conditions | Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 447 |
| Arms | 2 |
| Primary endpoint type | Binary |
| Results posted | Yes |
| Outcome measures posted | 17 |
| Statistical analyses posted | 2 |
| Lead sponsor | Teva Branded Pharmaceutical Products R&D, Inc. |
| Sponsor type | Industry |
| ClinicalTrials.gov | NCT00877006 |
2. Clinical Question
The study addresses whether bendamustine and rituximab (BR) should produce a more favorable first-line treatment result than the R-CHOP/R-CVP standard-treatment group in patients with advanced indolent non-Hodgkin's lymphoma or mantle cell lymphoma. The registered primary endpoint was complete response at the end of treatment.
Population
Patients with advanced indolent non-Hodgkin's lymphoma or mantle cell lymphoma receiving first-line treatment.
Intervention
Bendamustine and rituximab (BR).
Comparator
R-CHOP/R-CVP.
Primary question
Whether BR produces a difference in the percentage of participants with complete response at the end of the treatment period.
3. Trial Design
Bendamustine and Rituximab
- Bendamustine
- Rituximab
R-CHOP/R-CVP
- Rituximab
- Cyclophosphamide
- Vincristine
- Prednisone
- Doxorubicin
The intervention list posted on ClinicalTrials.gov for the registry includes bendamustine, rituximab, vincristine, prednisone, cyclophosphamide, and doxorubicin. The ClinicalTrials.gov record does not provide arm-specific treatment schedules or doses, so those details are not reconstructed here.
4. Endpoints
Registered Primary Endpoint
| Endpoint | Time frame | Type |
|---|---|---|
| Percentage of Participants With Complete Response (CR) at End of Treatment Period | 6 to 8 21 or 28-day cycles (18-32 weeks) | Binary |
The registry definition posted on ClinicalTrials.gov for complete response is: “CR=complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present pretherapy; protocol-specified positron emission tomography (PET) scan assessment criteria; (if the spleen and/or liver were enlarged on the basis of physical examination and/or anatomic imaging before treatment) the liver and/or spleen were considered normal size on physical examination and by anatomic imaging after therapy, with disappearance of all nodules related to lymphoma; (if the bone marrow was involved by lymphoma before treatment) the infiltrate must have cleared on subsequent bone marrow biopsies.”. The registry-reported definition ends at that point, so this page does not extend or reconstruct the remainder.
Posted Secondary Statistical Endpoints
| Endpoint | Time frame | Type | Analysis |
|---|---|---|---|
| Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period | Treatment Period: 18-32 weeks; Long-Term Follow-up Period: up to 5 years after the Treatment Period | Time-to-event | Stratified log-rank test; hazard ratio |
| Change From Baseline to End of Treatment in the Global Health Status Score of the EORTC 30-item Core Quality of Life Questionnaire (QLQ-C30) | Day 1 (prior to treatment), 32 weeks | Continuous | ANCOVA |
5. Primary Endpoint Results
ClinicalTrials.gov indicates that results were posted for the registered primary endpoint, but the ClinicalTrials.gov record does not provide a statistical-analysis record, treatment-group estimates, confidence interval, or P-value for that endpoint. Because the task requires every number to come only from the ClinicalTrials.gov record, no numerical complete-response comparison is reported here.
The absence of a registry-reported formal analysis record is analytically important. A binary endpoint cannot be reconstructed reliably from the fact that results were posted; the treatment-group counts or percentages and the prespecified comparison method are needed to quantify the result.
6. Secondary Results: Disease Progression, Relapse or Death
The first detailed statistical-analysis record concerns participants with disease progression, relapse or death at the end of the treatment period or during long-term follow-up. The analysis population was the set of randomized patients, defined in the registry as all patients randomly assigned to treatment.
Hazard ratio for progression, relapse or death
95% CI: 0.58–1.68 · P = 0.9677
BR vs R-CHOP/R-CVP · Stratified log-rank analysis
| Analysis feature | Reported value |
|---|---|
| Analysis population | Randomized patients; intent-to-treat |
| Groups compared | Bendamustine and Rituximab (BR) vs R-CHOP/R-CVP |
| Endpoint | Disease progression, relapse or death |
| Time frame | Treatment Period: 18-32 weeks; Long-Term Follow-up Period: up to 5 years after the Treatment Period |
| Method | Log Rank |
| Effect measure | Hazard Ratio (HR) |
| Estimate | 0.99 |
| 95% confidence interval | 0.58–1.68 |
| P-value | 0.9677 |
| Hypothesis type | Superiority |
| Stratification | Stratified log-rank test by preassigned standard treatment and lymphoma type |
An HR of 0.99 means that the estimated instantaneous rate of the composite event of progression, relapse or death was very close to the comparator rate under the fitted time-to-event comparison. Numerically, an HR of 0.99 corresponds to an estimated relative hazard that is 1% lower for BR than for R-CHOP/R-CVP.
The HR does not mean that 99% of participants avoided progression, relapse or death, nor does it provide a direct absolute difference in the proportion of participants experiencing an event. It is a relative time-to-event measure.
The 95% CI of 0.58–1.68 is wide relative to the point estimate. It describes uncertainty around the estimated hazard ratio under the analysis framework; it is not a range containing the outcomes that individual patients might experience.
The P-value of 0.9677 is evidence about the compatibility of the observed data with the tested statistical hypothesis. It is not a measure of the magnitude of the treatment effect. Effect magnitude and precision are better conveyed by the HR and its confidence interval.
Because this was a time-to-event endpoint, interpretation also depends on censoring and on the assumptions underlying the hazard-ratio framework. The ClinicalTrials.gov record specifies a stratified log-rank test but do not provide a separate proportional-hazards diagnostic or a detailed censoring analysis.
7. Secondary Results: Global Health Status
The second detailed statistical-analysis record evaluates change from baseline to 32 weeks in the global health status score of the European Organization for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire (EORTC QLQ-C30).
ANCOVA comparison
BR vs R-CHOP/R-CVP
Change from Day 1 (prior to treatment) to 32 weeks
| Analysis feature | Reported value |
|---|---|
| Outcome | Change from baseline to end of treatment in EORTC QLQ-C30 global health status score |
| Time points | Day 1 (prior to treatment), 32 weeks |
| Outcome type | Continuous; units on a scale |
| Analysis population | Randomized participants, intent-to-treat, who had data at both timepoints |
| Groups compared | Bendamustine and Rituximab (BR) vs R-CHOP/R-CVP |
| Method | ANCOVA |
| Hypothesis type | Superiority |
| P-value | 0.0005 |
| Analysis note | The hypothesis of interest is superiority of BR over standard treatment. |
The reported P-value of 0.0005 indicates the result of the specified ANCOVA comparison of change in global health status. It does not quantify the size of the difference between treatment groups.
Unlike the progression/relapse/death analysis, this endpoint is continuous rather than time-to-event. The appropriate effect-size interpretation would ordinarily focus on the adjusted difference in mean change, together with its confidence interval and the scale on which the questionnaire is measured.
The ClinicalTrials.gov record does not provide the adjusted group means, adjusted mean difference, standard error, or confidence interval. Those quantities therefore cannot be added or reconstructed here.
The analysis population is also narrower than a simple all-randomized comparison because participants needed data at both timepoints. This creates an important distinction from a pure ITT analysis of everyone randomized: the registry describes the population as randomized participants with observations at both timepoints.
8. Safety
The ClinicalTrials.gov record provides serious adverse-event counts by randomized treatment group as affected participants over the corresponding at-risk population.
| Safety measure | Bendamustine and Rituximab (BR) | R-CHOP/CVP |
|---|---|---|
| Serious adverse events | 60/221 | 49/215 |
The numerator is the number of affected participants and the denominator is the number at risk in the ClinicalTrials.gov record. These figures should not be converted into a different statistic or interpreted as an adjusted treatment effect. The ClinicalTrials.gov record does not provide a formal statistical comparison, confidence interval, exposure-adjusted incidence rate, or detailed serious-adverse-event taxonomy.
9. Statistical Methodology
Intention-to-treat analysis
The disease progression, relapse or death analysis explicitly uses randomized patients as the analysis population. The registry defines this intent-to-treat set as all patients randomly assigned to treatment. Analysing participants according to their randomized assignment preserves the principal comparison created by randomization.
Stratified log-rank test
The time-to-event analysis used a stratified log-rank test by preassigned standard treatment and lymphoma type. Stratification allows the treatment comparison to account for prespecified factors rather than treating all event times as if the groups were completely homogeneous with respect to those factors.
The log-rank framework compares the observed and expected pattern of events over follow-up. A stratified version performs this comparison while accounting for the prespecified strata.
Hazard ratio
The progression/relapse/death endpoint reports a hazard ratio. A hazard ratio compares the instantaneous event rates between groups within a time-to-event modelling framework. An HR below 1 indicates a lower estimated instantaneous event rate in the first-listed treatment group relative to the comparator; an HR above 1 indicates a higher estimated instantaneous event rate.
This is a relative time-to-event interpretation. It is not an absolute risk difference, probability of response, or statement about an individual participant.
ANCOVA
ANCOVA, or analysis of covariance, was used for the continuous EORTC QLQ-C30 global health status change endpoint. In a typical clinical-trial application, ANCOVA compares treatment groups while adjusting the outcome for a prespecified baseline covariate. This can improve precision when the baseline measurement is associated with the follow-up outcome.
The exact covariates and model specification used in the trial are not reported in the ClinicalTrials.gov record, so this equation is presented as the general statistical concept rather than as a reconstruction of the trial's full model.
Confidence intervals
The progression/relapse/death analysis reports a two-sided 95% confidence interval of 0.58–1.68 around the hazard ratio. A confidence interval communicates statistical precision around the estimated treatment effect. It should be interpreted together with the point estimate rather than as a probability statement about where the true parameter lies.
P-values
The analyses posted on ClinicalTrials.gov report P-values of 0.9677 and 0.0005. A P-value measures the strength of evidence against a specified null hypothesis under the assumptions of the statistical test. It does not measure clinical importance, effect size, or the probability that the null hypothesis is true.
10. Statistical Methods Explained
Why was a stratified log-rank test used?
The progression, relapse or death endpoint is a time-to-event outcome, so a method that uses the timing of events and censoring is appropriate. The registry-reported analysis specifically used a stratified log-rank test, with strata defined by preassigned standard treatment and lymphoma type. This incorporates those prespecified factors into the comparison.
What does an HR of 0.99 mean?
An HR of 0.99 means the estimated instantaneous event rate for progression, relapse or death was approximately 1% lower in the BR group than in the R-CHOP/R-CVP group under the reported time-to-event comparison. It does not mean that the event probability was exactly 1% lower.
Why is the confidence interval important?
The HR of 0.99 is only one estimate. The 95% CI of 0.58–1.68 shows that the estimate has substantial statistical uncertainty. The interval is therefore essential to understanding the precision of the reported HR; focusing only on the point estimate would give an incomplete picture.
Why doesn't P = 0.9677 measure the treatment effect?
A P-value is tied to a hypothesis test, not to the magnitude of an effect. P = 0.9677 does not mean that the treatment effect is “96.77%” or that the groups are “96.77% the same.” The treatment effect is described by the HR, while its statistical precision is described by the confidence interval.
Why was ANCOVA used for the quality-of-life endpoint?
The EORTC QLQ-C30 global health status change is a continuous outcome. ANCOVA is commonly used for continuous clinical-trial outcomes because it can compare treatment groups while accounting for baseline outcome measurements. The ClinicalTrials.gov record identifies ANCOVA as the method but does not provide the full model specification.
Why is the ANCOVA analysis population important?
The registry specifies randomized participants with data at both timepoints. That requirement means the analysis does not simply consist of every randomized participant regardless of missing follow-up data. The ClinicalTrials.gov record does not specify an imputation method, so missing-data handling cannot be reconstructed.
11. Stratification and Analysis Populations
The ClinicalTrials.gov record gives two particularly important pieces of design information: the time-to-event analysis was stratified by preassigned standard treatment and lymphoma type, and the analyses used an ITT framework for randomized participants.
| Feature | Supplied trial information |
|---|---|
| Randomization | Randomized allocation |
| Time-to-event population | Randomized patients; intent-to-treat |
| Time-to-event stratification | Preassigned standard treatment and lymphoma type |
| Quality-of-life population | Randomized participants who had data at both timepoints |
| Quality-of-life method | ANCOVA |
These distinctions illustrate why “the trial population” is not always identical to “the population contributing to every analysis.” Randomization defines the primary causal comparison, while individual endpoints can have additional analysis-population requirements.
12. Missing Data and Censoring
Time-to-event endpoint
The progression, relapse or death endpoint is inherently a time-to-event outcome. Participants who have not experienced the event by the end of their available follow-up can contribute information up to their censoring time. The ClinicalTrials.gov record does not describe the censoring rules, the number of censored observations, or any sensitivity analyses for censoring assumptions.
Quality-of-life endpoint
The EORTC QLQ-C30 analysis requires data at both Day 1 and 32 weeks according to the registry-reported analysis-population definition. The registry information provided does not specify how missing questionnaires were imputed or whether sensitivity analyses were conducted.
13. Multiplicity and Hypothesis Testing
the ClinicalTrials.gov record identifies one registered primary endpoint and two posted statistical analyses, both labeled secondary. The ClinicalTrials.gov record does not describe an alpha-allocation strategy, endpoint hierarchy beyond the primary/secondary labels, multiplicity adjustment, or an interim-analysis plan.
| Endpoint / analysis | Role in the ClinicalTrials.gov record | Method |
|---|---|---|
| Complete response at end of treatment | Registered primary endpoint | Formal statistical method not reported |
| Progression, relapse or death | Secondary analysis | Stratified log-rank test; HR |
| EORTC QLQ-C30 global health status change | Secondary analysis | ANCOVA |
Because the ClinicalTrials.gov record does not state how multiple endpoints or analyses were controlled, the reported P-values should be interpreted according to their specific analysis records rather than assuming an unstated familywise error-control procedure.
14. Design Topics Not Reported in the Supplied Data
Non-inferiority margin
No non-inferiority hypothesis or margin is reported in the ClinicalTrials.gov record. The statistical analyses posted on ClinicalTrials.gov are labeled superiority.
Crossover
No crossover procedure is reported in the ClinicalTrials.gov record.
Factorial design
The design model is parallel, with two arms. No factorial structure is reported.
Bayesian methods
No Bayesian statistical method is reported in the ClinicalTrials.gov record.
15. Timeline
Trial start
The ClinicalTrials.gov record lists 2009-04-30 as the study start date.
Primary completion
The ClinicalTrials.gov record lists 2012-03-31 as the primary completion date.
Final registry status
The study is listed as completed, with results posted and 17 outcome measures reported.
16. Reading the Progression, Relapse or Death Result
The reported HR of 0.99 is close to 1. In a hazard-ratio framework, an HR of 1 represents equal instantaneous event rates between groups. An HR of 0.99 therefore represents a very small estimated relative difference in the direction of BR.
The 95% CI of 0.58–1.68 extends both below and above 1. The interval therefore encompasses a range of possible relative hazard values around the point estimate. It also demonstrates why the point estimate alone should not be treated as the complete statistical result.
The reported P-value of 0.9677 is associated with the specified superiority analysis. It is not a measure of the probability that BR and R-CHOP/R-CVP are identical, and it does not quantify the clinical size of a treatment difference.
The result comes from a stratified log-rank comparison and is accompanied by a hazard ratio. The analysis population is randomized patients under the stated ITT definition, and the stratification variables are preassigned standard treatment and lymphoma type.
17. Interpreting the Quality-of-Life Analysis
The EORTC QLQ-C30 global health status analysis illustrates a different statistical problem from progression, relapse or death. The outcome is continuous and is defined as change from baseline to 32 weeks. ANCOVA was used, and the reported P-value was 0.0005.
What is reported
The ClinicalTrials.gov record provides the endpoint definition, time points, analysis population, treatment comparison, ANCOVA method, superiority hypothesis, and P-value of 0.0005.
What is not reported
The ClinicalTrials.gov record does not provide adjusted mean changes, a treatment-group difference, standard error, confidence interval, or the full ANCOVA covariate specification.
This distinction matters because a small P-value can establish evidence against a null hypothesis without telling the reader how large the difference was on the questionnaire scale. For a continuous outcome, the estimated difference and its confidence interval are central to understanding magnitude and precision.
18. Why This Trial Matters Statistically
This trial is useful as a teaching example because the ClinicalTrials.gov record places several fundamental clinical-trial methods side by side: randomized allocation, a binary response endpoint, a time-to-event endpoint, a continuous quality-of-life endpoint, ITT analysis, stratified log-rank testing, hazard-ratio estimation, and ANCOVA.
| Concept | How it appears in R-CVP |
|---|---|
| Randomization | The trial uses randomized allocation in a parallel two-arm phase 3 design. |
| Binary endpoint | The registered primary endpoint is the percentage of participants with complete response at the end of treatment. |
| Time-to-event endpoint | Progression, relapse or death is analysed over the treatment and long-term follow-up periods. |
| ITT analysis | The progression/relapse/death analysis uses randomized patients as defined by the registry. |
| Stratified analysis | The log-rank analysis is stratified by preassigned standard treatment and lymphoma type. |
| Hazard ratio | The progression/relapse/death analysis reports HR 0.99 with a 95% CI of 0.58–1.68. |
| Confidence interval | The time-to-event analysis reports a two-sided 95% confidence interval. |
| P-value | The analyses posted on ClinicalTrials.gov report P = 0.9677 and P = 0.0005. |
| ANCOVA | The EORTC QLQ-C30 global health status change endpoint is analysed using ANCOVA. |
| Longitudinal measurement | The quality-of-life analysis compares Day 1 with 32 weeks. |
19. Limitations
- Primary-endpoint statistical detail: the ClinicalTrials.gov record identifies the complete-response endpoint as primary and state that results were posted, but they do not provide the primary endpoint's treatment-group estimates or formal statistical-analysis record.
- Limited statistical-analysis records: the ClinicalTrials.gov recordset contains two detailed statistical analyses, and both are labeled secondary.
- Incomplete effect-size reporting for ANCOVA: the quality-of-life analysis provides P = 0.0005 but not the adjusted treatment difference or its confidence interval.
- Wide uncertainty for the hazard ratio: the progression/relapse/death HR is 0.99 with a 95% CI of 0.58–1.68, so the point estimate should not be interpreted without the interval.
- Unknown censoring details: the ClinicalTrials.gov record does not describe censoring rules or sensitivity analyses for the time-to-event endpoint.
- Unknown missing-data strategy: the quality-of-life analysis requires observations at both timepoints, but the ClinicalTrials.gov record does not describe imputation or sensitivity analyses.
- Multiplicity: the ClinicalTrials.gov record does not state an alpha-allocation or multiplicity-adjustment strategy for the primary and secondary endpoints.
- Unreported design details: the ClinicalTrials.gov record does not report a non-inferiority margin, crossover strategy, interim analysis plan, or Bayesian method.
- Safety detail: the ClinicalTrials.gov record is limited to serious adverse events by arm and does not provide a detailed event-level safety analysis.
20. What This Analysis Can and Cannot Establish
What the ClinicalTrials.gov record establishes
The trial was randomized, parallel, open-label, phase 3, enrolled 447 participants, and compared BR with R-CHOP/R-CVP. The ClinicalTrials.gov record also provide two secondary statistical analyses with their methods and reported results.
What the ClinicalTrials.gov record does not establish
They do not provide the numerical result or formal analysis of the registered complete-response primary endpoint, nor do they provide enough information to reconstruct the full ANCOVA treatment effect.
This distinction is central to responsible trial interpretation. A statistically complete analysis requires more than knowing that a registry contains posted results. Each endpoint needs its numerator or estimated treatment effect, analysis population, statistical method, uncertainty measure where available, and testing framework before a quantitative conclusion can be reconstructed.
21. Related Statistical Tutorials
Learn more about the methods used in this trial:
22. Related Statistical Calculators
23. Sources
- ClinicalTrials.gov: NCT00877006, the official registry record for the R-CVP trial.
- Linked publication: PubMed record for PMID 24591201.
- Linked publication: PubMed record for PMID 30811293.
- Linked publication: PubMed record for PMID 26875824.
Continue through Clinical Biostats
Use the related tutorials and statistical calculators to explore the methods that appear in randomized clinical-trial analysis.
24. Record Summary
R-CVP is a phase 3 randomized parallel-group trial comparing bendamustine and rituximab with R-CHOP/R-CVP in advanced indolent non-Hodgkin's lymphoma or mantle cell lymphoma. The registered primary endpoint is the percentage of participants with complete response at the end of treatment, measured after 6 to 8 21 or 28-day cycles (18-32 weeks). The ClinicalTrials.gov record also contain two detailed secondary statistical analyses: a stratified log-rank analysis of progression, relapse or death with HR 0.99 (95% CI 0.58–1.68; P = 0.9677), and an ANCOVA analysis of change in EORTC QLQ-C30 global health status with P = 0.0005.
The statistical lesson is that different clinical-trial endpoints require different analytical frameworks. The time-to-event endpoint uses randomized patients, stratification, a log-rank comparison, and a hazard ratio. The continuous quality-of-life endpoint uses ANCOVA and requires observations at both specified timepoints. Meanwhile, the ClinicalTrials.gov record does not provide enough numerical information to reconstruct the formal primary complete-response comparison. Keeping those distinctions explicit prevents a secondary analysis from being mistaken for the primary result and prevents P-values from being interpreted as measures of effect size.