Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (NCT01014208), a randomized phase 3 study. The primary outcome is Progression-free Survival as Assessed by Independent Reviewers.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-arm phase 3 trial listed as completed, with enrollment of 447. The registry record describes an open-label design, with no masking. Participants were assigned to ofatumumab plus chemotherapy or rituximab plus chemotherapy. The arm descriptions identify DHAP as the chemotherapy regimen and state that participants in each arm received the same regimen and dose of the antibody assigned to that arm.

The arm descriptions also say investigators prospectively chose to treat all of their subjects with one of the two DHAP combinations. How that statement relates to the trial’s listed randomized allocation is not explained in the registry record. The randomization procedure, including any details about sequence generation or concealment, is not reported in the registry record. It is therefore not possible to resolve that description or infer additional design details from it.

Participants and analysis set

The trial concerned people with CD20-positive diffuse large B cell lymphoma that had relapsed or persisted after first-line rituximab combined with anthracycline-based chemotherapy and who were eligible for autologous stem cell transplant. The primary outcome’s stated analysis population was the intent-to-treat population, defined in the registry as randomized participants who commenced study therapy by receiving at least one dose of a study drug. This definition does not include randomized participants who never started study therapy.

The primary endpoint was progression-free survival assessed by independent reviewers. The registry lists an assessment period of up to 5 years. Arm sizes in the primary result were 223 for rituximab plus chemotherapy and 222 for ofatumumab plus chemotherapy. The record does not report the original sample-size justification, the planned number of events, or details of any interim analyses. Those design features should not be inferred from the later planning illustrations.

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: Eligible participants were randomized to receive either rituximab or ofatumumab in addition to salvage chemotherapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants who were randomized and commenced study therapy (at least one dose of a study drug)

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 Progression-free Survival as Assessed by Independent Reviewers, measured over From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years).

Progression-free survival was defined as the time from randomization until stable disease after two cycles of salvage chemotherapy, progression, or death, whichever occurred first. Stable disease meant failure to meet the criteria for complete or partial response without meeting the criteria for progressive disease. Progression was based on independent reviewers’ assessments using imaging and the Revised Response Criteria for Malignant Lymphoma. The registry describes follow-up for this outcome for up to 5 years.

A time-to-event endpoint records how long it takes for a specified event to occur, while allowing participants who have not had an event by the end of available follow-up to contribute information up to that point. In general, this approach can use follow-up information from participants whose event times are not yet known. The registry’s endpoint definition is important to interpretation: stable disease after two cycles is counted as an endpoint event, alongside progression and death. It is therefore not simply a measure of progression or death.

The registry reports the median time to the defined event in each group and a hazard ratio from a stratified log-rank analysis. The median describes the time by which half of the relevant event-time distribution has occurred, subject to the analysis and follow-up. The hazard ratio compares event rates over follow-up under the model used; it is not a direct comparison of median times. Independent review of disease assessments is intended to base progression determinations on reviewers separate from the treating investigators, but further details of review procedures are not reported in the registry record.

7. Results Posted in the Registry

• Rituximab + Chemotherapy vs Ofatumumab + Chemotherapy: hazard ratio 1.12 (95% CI 0.89–1.42), reported p = 0.333 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Event-free Survival

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Stratified log-rank test); it was not recalculated.
• Result:
  • Rituximab + Chemotherapy vs Ofatumumab + Chemotherapy: hazard ratio 1.10 (95% CI 0.90–1.36), reported p = 0.346 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Rituximab + Chemotherapy vs Ofatumumab + Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Stratified log-rank test); it was not recalculated.
• Result:
  • Rituximab + Chemotherapy vs Ofatumumab + Chemotherapy: hazard ratio 0.90 (95% CI 0.70–1.15), reported p = 0.377 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Rituximab + Chemotherapy vs Ofatumumab + Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ofatumumab + Chemotherapy: 96.0% (120/125) versus 90.3% (121/134) on control; risk difference 5.7 percentage points (95% CI -0.4 to 11.8), risk ratio 1.06 (1.00–1.14); unadjusted two-proportion z-test p = 0.071.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ofatumumab + Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes provide context for the primary comparison rather than an independent confirmation of a particular treatment effect. Event-free survival and overall survival are time-to-event measures with definitions that differ from the primary progression-free survival endpoint. Their reported hazard ratios and confidence intervals do not show a statistically clear separation between groups, and their intervals include 1. The direction and size of a point estimate should not be treated as decisive when the estimate remains imprecise.

The stem-cell mobilization outcome concerns whether participants reached a specified collection threshold. Its sponsor-reported odds ratio also has a wide confidence interval that includes 1. It measures a different aspect of the treatment course from the survival outcomes, so it cannot establish or overturn the primary endpoint result. Other listed outcomes include response, transplant completion, and quality-of-life measures, but results for those outcomes are not reported in the registry record summarized for this analysis.

Secondary outcomes are often examined in multiples, and repeated testing increases the chance that at least one result may appear noteworthy by chance. Unless a multiplicity strategy is specified, nominal p-values across several outcomes should not be interpreted as if each were the sole planned test. The registry record does not report a multiplicity adjustment or hierarchy for these analyses. This uncertainty gives secondary findings less inferential weight than a clearly specified primary analysis, especially when the secondary estimates are imprecise or use distinct outcome definitions.

Across the posted secondary analyses, the broad pattern is that estimates remain uncertain and do not establish a clear group difference. That pattern is compatible with the primary result, but it does not prove equality of treatments, and it cannot fill gaps where outcome results or analysis details are absent. Each endpoint should be considered in light of its definition, analysis population, method, and confidence interval.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy
• Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant
• Event-free Survival
• Overall Survival (OS)
• Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood
• Number of Participants Completing Autologous Stem Cell Transplant (ASCT)
• Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment
• Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment

9. Statistical Interpretation

10. Statistical Methods Explained

Time-to-event summaries

The primary outcome and the reported event-free and overall survival outcomes are time-to-event measures. In general, these methods use both the timing of events and the duration of observed follow-up. Participants without a recorded event by the end of their available observation may be censored: their data indicate that they remained without the event until their last relevant observation, but do not establish what happened afterward. The registry record does not report detailed censoring rules or how missing follow-up was handled.

The median time is a distributional summary: it identifies the time at which the estimated event-time distribution reaches its midpoint. It does not describe every participant’s experience, and it is not itself a comparison adjusted for follow-up patterns. The registry reports a median and a 95% confidence interval for each arm. Comparing two medians informally is not equivalent to testing the full time-to-event distributions, and the registry’s comparative analysis instead reports a hazard ratio from a stratified log-rank test.

Hazard ratios and log-rank tests

In general, a hazard is the rate at which an event occurs among people who have not yet experienced it, at a given point in follow-up. A hazard ratio expresses the relative hazards between groups under the comparison’s stated orientation. A value of 1 corresponds to equal estimated hazards; values on either side indicate different estimated directions. A hazard ratio is not a ratio of median survival times, and it does not directly state how many months separate the groups.

The primary comparison used a stratified log-rank test. In general, the log-rank approach compares event-time patterns over follow-up, and stratification allows the comparison to account for specified strata. The strata used in this trial are not reported in the registry record. The registry gives a hazard ratio, its 95% confidence interval, and a p-value for this analysis. The test’s p-value reflects how inconsistent the data are with its null hypothesis under the analysis assumptions; it is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of a difference.

The primary hazard ratio is reported as rituximab plus chemotherapy versus ofatumumab plus chemotherapy. For event-free survival and overall survival, the registry likewise reports the comparison in that order. The comparison direction should be checked before interpreting whether an estimate above or below 1 favors either group statistically. In all three time-to-event comparisons, the confidence interval includes 1, so the reported estimates do not distinguish a relative hazard of 1 from a range of other values at the stated confidence level.

What the endpoint definition changes

The primary progression-free survival definition includes stable disease after two cycles of salvage chemotherapy as an event, as well as progression or death. That makes the endpoint broader than progression or death alone. The secondary event-free survival definition also includes stable disease after completion of two cycles, and additionally includes commencement of a new treatment for diffuse large B cell lymphoma. Because endpoint definitions differ, their results are related but not interchangeable. A finding for one endpoint should not automatically be carried over to another.

Independent reviewers assessed progression for the primary outcome using imaging and the Revised Response Criteria for Malignant Lymphoma. In general, independent assessment may reduce reliance on judgments made solely by treating investigators. The registry does not report details such as reviewer blinding, disagreement resolution, or assessment schedules beyond the endpoint timeframe, so those features cannot be evaluated from the record.

Binary outcome analysis

The stem-cell mobilization endpoint counted participants who were able to mobilize at least 2 million CD34+ cells per kilogram from peripheral blood. The posted counts were 121 of 134 for rituximab plus chemotherapy and 120 of 125 for ofatumumab plus chemotherapy. The sponsor-reported comparison used a Cochran-Mantel-Haenszel odds ratio. In general, this method estimates an association while accounting for strata; the strata used are not reported in the registry record. An odds ratio is a comparison of odds, not a direct comparison of probabilities, and it can differ from a risk difference or risk ratio.

A simple unadjusted recalculation from summary counts can be useful as a check, but it does not reproduce an analysis that accounts for strata or other design features. For that reason, the sponsor’s reported analysis is the relevant registry result for this outcome. The unadjusted p-value should not be treated as interchangeable with the sponsor’s p-value, and the registry result should be interpreted using its own stated method and confidence interval.

Interpretation of uncertainty

A confidence interval describes a range of estimates compatible with the observed data under the analysis procedure. In general, a 95% confidence interval reflects the long-run coverage of the method under its assumptions; it is not a guarantee that a particular interval contains the true effect with a stated probability. A narrower interval indicates greater statistical precision than a wider interval, but precision alone does not establish importance or eliminate potential bias.

The p-values, hazard ratios, medians, and confidence intervals answer related but distinct questions. The point estimate gives a single estimate under the chosen method; the interval expresses uncertainty around it; the p-value evaluates compatibility with a null hypothesis. No single value should be read as a complete account of the evidence. The registry record does not report the full statistical analysis plan, model diagnostics, missing-data approach, or multiplicity strategy, limiting assessment of assumptions and the broader inferential context.

11. Confidence Intervals and Precision

The primary hazard ratio was 1.12, with a 95% confidence interval from 0.89 to 1.42. The interval spans 1, the value corresponding to equal hazards under the comparison’s orientation. It also extends to estimates on either side of 1, so the result does not pin down the direction of the relative hazard. The p-value was 0.333, consistent with the uncertainty reflected by the interval rather than evidence of a sharply determined group difference.

The arm-specific median estimates also have uncertainty. Median progression-free survival was 2.14 months in the rituximab group, with a 95% confidence interval from 1.64 to 4.37 months, and 1.81 months in the ofatumumab group, with a 95% confidence interval from 1.54 to 2.53 months. These intervals describe uncertainty in each arm’s median estimate. They are not a confidence interval for the difference between medians, and overlap or non-overlap of separate intervals is not a substitute for the reported comparative analysis.

Precision across outcomes

The secondary time-to-event estimates also have intervals that include 1. The event-free survival interval runs from 0.90 to 1.36, and the overall survival interval from 0.70 to 1.15. These ranges leave room for different relative event rates, and their widths indicate that the estimates are not exact. The mobilization odds-ratio interval, from 0.83 to 9.50, is particularly broad in relation to its point estimate; it permits a wide range of possible associations under the sponsor’s method.

In general, confidence intervals are affected by the amount and distribution of observed information, including the number and timing of events for time-to-event outcomes. The registry reports arm sizes and endpoint estimates, but it does not give all details needed to evaluate information at each time point or assumptions behind the analyses. Accordingly, the precision discussion should focus on the reported intervals rather than infer unreported event counts or follow-up patterns.

Confidence intervals quantify statistical uncertainty under an analysis; they do not account automatically for bias from open-label treatment, outcome measurement, missing data, or analysis choices. Nor do they establish whether any possible difference is meaningful in clinical terms. The posted intervals are best read as ranges of estimates supported by the analysis, with substantial uncertainty remaining about the size and direction of comparative effects.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not a reconstruction of the trial’s original design. For time-to-event outcomes, the entries are total events required, calculated using the Schoenfeld approach. For other outcomes, the entries are participants per arm. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider detecting the stated fraction of the observed effect.

The 80% power column represents the number of events or participants that a future study would need, under those assumptions, to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column applies the same idea with a higher chance of detection, and therefore generally calls for more information. These are planning targets, not results from the completed trial. This is not observed power.

Rows based on 100%, 75%, and 50% of the observed effect illustrate how planning needs change if the effect a future study aims to detect is smaller than the point estimate used in the calculation. Smaller effects are harder to distinguish from random variation, so they require more participants or events for the same target power. The required event totals for survival outcomes are not participant totals; the number of people needed to generate those events depends on follow-up and event occurrence, which are not specified by these calculations.

The original trial’s sample-size justification, intended target power, design effect, and event target are not reported in the registry record. The illustrations should therefore be read only as hypothetical planning aids under their listed assumptions, not as evidence about whether the completed trial was adequately powered according to its original protocol.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.120, so ln(HR) = 0.1133.
2. d = 4 × (1.96 + 0.842)² / [ln(1.120)]² = 2,444.5, rounded up to 2,445 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.12                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1014208)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 2,445 (80% power), 3,273 (90% power)
 75% of observed effect: events = 4,346 (80% power), 5,818 (90% power)
 50% of observed effect: events = 9,778 (80% power), 13,090 (90% power)
Simulated power with 2,445 events: 0.799 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

For the primary outcome, the registry reports a hazard ratio of 1.12, a 95% confidence interval from 0.89 to 1.42, and p = 0.333 using a stratified log-rank test. The arm-specific medians and the reported comparative analysis describe different aspects of the time-to-event data: the medians summarize each group, while the hazard ratio compares event rates over follow-up under the stated analysis. The primary sponsor-reported result is the appropriate comparative result to interpret.

For the mobilization outcome, the sponsor used a Cochran-Mantel-Haenszel odds ratio of 2.57, with a 95% confidence interval from 0.83 to 9.50. A simple unadjusted recalculation from the posted counts uses a different method and estimand. Its risk-difference estimate and unadjusted p-value should not be substituted for the sponsor’s stratified odds-ratio analysis or treated as a reproduction of it. The registry does not report the strata used for the sponsor’s analysis.

The registry record does not identify a discrepancy for these results. In general, a recalculation from summary counts is less informative about an adjusted analysis than the analysis that uses the trial’s specified method and data structure. The sponsor’s reported results should therefore be read according to their stated methods, while recognizing that the record does not include enough detail to independently assess every modeling or stratification choice.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including response measures, event-free and overall survival, stem-cell mobilization, transplant completion, and quality-of-life measures. Testing several outcomes can increase the overall chance of a false-positive finding if each is assessed separately without adjustment. In general, multiplicity is addressed through approaches such as prespecifying a hierarchy or adjusting the testing threshold, but no such strategy is reported in the registry record. The record also does not state whether the reported secondary analyses were confirmatory or exploratory. Their p-values should therefore be read as outcome-specific results, not as evidence that a family of outcomes has been controlled for multiple testing.

Missing data and censoring

The primary endpoint definition and its assessment period are described, but the registry record does not report how missing outcome assessments, loss to follow-up, treatment discontinuation, or incomplete follow-up were handled. For time-to-event outcomes, censoring rules and assumptions are important because the analysis relies on available follow-up for participants without a recorded event. The registry does not provide enough information to assess whether those assumptions were met or whether sensitivity analyses were conducted.

Analysis populations and protocol details

The primary population is defined as randomized participants who commenced study therapy by receiving at least one dose of a study drug. The registry record does not report a separate analysis of all randomized participants regardless of treatment commencement, nor does it give outcome-specific analysis populations for every posted secondary result. The record also does not report the statistical analysis plan, the planned handling of protocol deviations, the randomization details, or whether interim analyses were conducted. These omissions limit independent assessment of prespecification and possible analysis choices.

These gaps do not by themselves show that the analyses are invalid. They mean that the posted results cannot answer questions about unreported procedures. Interpretation should remain anchored to the stated endpoint definitions, analysis methods, populations, and uncertainty intervals, without assuming that a particular missing-data, multiplicity, or interim-analysis approach was used.

16. 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: febrile neutropenia (13.5%), vomiting (5.8%), thrombocytopenia (5.4%), blood creatinine increased (5.4%), renal failure acute (5.4%).

The registry reports serious adverse events for 115 of 223 participants in the rituximab plus chemotherapy group and 118 of 222 participants in the ofatumumab plus chemotherapy group. It reports other adverse events for 217 of 223 and 215 of 222 participants, respectively. These are counts of participants, not counts of individual event episodes. The registry lists febrile neutropenia at 13.5% as the most frequent serious adverse-event term, followed by vomiting at 5.8%; thrombocytopenia, increased blood creatinine, and acute renal failure at 5.4% each; and pyrexia at 4.9%.

These figures describe what was recorded in the trial and do not, by themselves, establish that an event was caused by a particular treatment. The record does not provide comparative statistical analyses for the adverse-event categories in the registry record, and death counts are not reported. A complete safety comparison would also depend on definitions, exposure time, event severity and duration, and how events were collected. Those details are not reported in the registry record, so the counts should be read descriptively and not as a complete account of comparative safety.

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

The registry’s primary analysis estimates progression-free survival using an endpoint that counts stable disease after two cycles, progression, or death. The two arm-specific median estimates were 2.14 months and 1.81 months. The reported hazard ratio was 1.12, with a 95% confidence interval from 0.89 to 1.42 and p = 0.333. The interval includes the null value of 1, and the estimate is not sufficiently precise to establish a clear difference in relative event rates.

The secondary event-free survival, overall survival, and stem-cell mobilization analyses also have confidence intervals that include their relevant null values. These results do not establish a clear comparative advantage on the outcomes posted. They also do not prove the groups are identical: absence of a statistically clear difference is not equivalent to evidence of equivalence or non-inferiority. The registry does not report a non-inferiority or equivalence framework for the primary analysis.

What it does not establish

The estimates do not determine whether a difference would matter clinically, because clinical importance depends on context beyond statistical significance and is not defined in the registry record. The results do not establish the outcome for individuals, and group-level medians or hazard ratios cannot predict an individual participant’s course. Nor should a point estimate alone be described as the effect that would necessarily occur in another population or setting.

Interpretation is limited to the trial population and the treatment comparisons described: ofatumumab plus DHAP versus rituximab plus DHAP in participants with the specified disease history who were eligible for transplant. The open-label design, registry reporting gaps, and missing information about analysis details leave uncertainty about some aspects of conduct and inference. The posted outcomes also do not cover every listed secondary endpoint. The statistical results therefore support a bounded conclusion: the registry reports no statistically clear separation in the primary comparison, with uncertainty remaining about the direction and size of possible differences.

18. Why This Trial Matters Statistically

This trial is statistically useful for illustrating the distinction between descriptive summaries and comparative analyses. The reported arm medians give a concise picture of each group’s event-time distribution, while the hazard ratio and stratified log-rank test address the comparison across follow-up. The primary confidence interval includes 1, showing why a point estimate alone is not enough to characterize the result.

The endpoint definition also matters. Progression-free survival includes stable disease after two cycles as an event, in addition to progression and death. Event-free survival has a different event definition, including new treatment for diffuse large B cell lymphoma. Even when outcomes are related, changing which events count can change the question being answered. Clear reading requires attending to those definitions rather than treating all survival labels as interchangeable.

The registry also demonstrates how method choice affects interpretation of a binary outcome. The sponsor reports an odds ratio using a stratified method, while a simple recalculation from summary counts is unadjusted and uses a different measure. These analyses are not interchangeable. More generally, a transparent account of estimands, strata, analysis populations, missing-data handling, and multiplicity is essential for readers to assess how results were produced.

Finally, planning calculations based on observed effects are not the same as a trial’s original design justification. They can illustrate how smaller target effects require more information under stated assumptions, but they cannot recover the rationale for the completed study. Keeping that distinction clear prevents planning examples from being mistaken for evidence about the trial’s achieved power or protocol intent.

19. 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 registry record leaves several trial-specific questions unanswered. It lists randomized allocation and a parallel-arm structure, yet the arm descriptions say investigators prospectively chose to treat all their subjects with one regimen. The record does not explain how these statements fit together, and it does not report the randomization procedure or allocation concealment. Masking is listed as none, which may matter for outcomes involving investigator assessment or participant-reported measures; the primary endpoint used independent reviewers, but details of their review process are not reported.

The primary analysis population excludes randomized participants who did not commence study therapy, according to the registry’s stated definition. The record does not give the number of such participants or report an analysis of all randomized participants regardless of treatment commencement. Outcome-specific populations for the secondary analyses are not fully described. Missing-data handling, censoring details, sensitivity analyses, and the assumptions used in the time-to-event models are also not reported.

The registry does not report the original sample-size rationale, the intended event target, a multiplicity plan, or whether interim analyses took place. These absences limit assessment of prespecification and the role of the multiple secondary outcomes. The sponsor’s stratified analysis for mobilization is reported, but the strata are not identified in the record, making the adjustment difficult to evaluate independently.

Finally, safety results are descriptive in the available record: comparative adverse-event analyses and death counts are not reported. Several listed secondary outcomes have no results in the registry record for this analysis. These limitations do not establish that a problem occurred; they define what cannot be assessed from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma — NCT01014208.
• Registry record last updated 2015-08-07; status last verified 2015-02.
• Results first posted 2014-10-16.
• 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.

23. Record Summary

NCT01014208 was a completed randomized, open-label, parallel-arm phase 3 trial with enrollment of 447. It compared ofatumumab plus DHAP salvage chemotherapy with rituximab plus DHAP in people with relapsed or refractory CD20-positive diffuse large B cell lymphoma who were eligible for autologous stem cell transplant after first-line rituximab and anthracycline-based chemotherapy.

The primary outcome was progression-free survival assessed by independent reviewers. Median estimates were 2.14 months for rituximab plus chemotherapy and 1.81 months for ofatumumab plus chemotherapy. The reported hazard ratio was 1.12, with a 95% confidence interval from 0.89 to 1.42 and p = 0.333. The interval includes 1, leaving uncertainty about the direction and size of any comparative difference.

Posted secondary analyses covered event-free survival, overall survival, and stem-cell mobilization. Their estimates also remain uncertain. The registry record does not report several details needed for fuller evaluation, including the original sample-size justification, multiplicity strategy, missing-data approach, and randomization procedure.