Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma (NCT00867087), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy.

2. Clinical Question

The clinical question is about response before a planned transplant pathway, not a randomized comparison of treatment strategies. The study also listed outcomes concerning progression-free survival, stem-cell mobilization, transplantation, event-free survival after transplantation, complete response after 3 cycles, and overall survival. Those questions broaden the outcomes under consideration, but they do not change the primary endpoint or make the study comparative.

3. Trial Design

This was a Phase 2, open-label, single-arm, non-randomized study of inotuzumab ozogamicin plus rituximab in relapsed or refractory diffuse large B-cell lymphoma. The official title specifies CD22-positive disease and eligibility for autologous stem cell transplantation. The listed regimen combined rituximab 375 mg/m^2 with inotuzumab ozogamicin 1.8 mg/m^2, administered before transplantation. Enrollment was 64, and the registry status is completed.

Because all participants were assigned to the same regimen and there was no control arm, the design can describe outcomes among participants in the study but cannot estimate a randomized between-group treatment contrast. The record identifies no masking. Open-label conduct means the treatment assignment was not masked, but details of how this may have affected outcome assessment are not reported in the registry record.

The primary endpoint was the percentage achieving complete or partial response after 3 cycles. The stated timeframe was up to 2 years, including 9 weeks of 3 21-day cycles and assessments every 3 to 6 months during long-term follow-up. The endpoint description uses National Cancer Institute International Response Criteria for non-Hodgkin's lymphoma. The primary analysis population was intention-to-treat, including all enrolled participants; the endpoint included confirmed and unconfirmed responses.

Secondary outcomes covered several distinct stages and types of outcome: progression-free survival estimates at 6 months and 2 years; response combined with successful mobilization of peripheral blood stem cells; successful mobilization; receipt of autologous stem cell transplantation; event-free survival after transplantation; complete response after 3 cycles; and overall survival. The registry lists 11 outcome measures. The timing, definitions, and analysis details for every secondary outcome are not reported in the registry record.

The study began on 2009-06-08, and primary completion was recorded as 2012-10-31. Further information on eligibility criteria, treatment delivery, follow-up procedures, and protocol deviations is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population - included all participants enrolled into the study. Response includes confirmed CR/PR and unconfirmed CR/PR.

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.

Population: Safety population - included participants who received at least 1 dose of study medication (rituximab or inotuzumab ozogamicin).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) After 3 Cycles of Inotuzumab Ozogamicin Plus Rituximab Therapy, measured over Up to 2 years (9 weeks of 3 21-day cycles and every 3 to 6 months during the long-term follow-up period).

The primary endpoint is the percentage of participants achieving complete response or partial response after 3 cycles of the combination. It summarizes the proportion of the intention-to-treat population meeting the registry’s response criteria, including both confirmed and unconfirmed responses. The endpoint timeframe is stated as up to 2 years, with the initial 9 weeks covering 3 21-day cycles and additional assessments every 3 to 6 months during long-term follow-up.

Complete response was defined using clinical, radiographic, organ, and bone marrow findings. The criteria include no detectable clinical or radiographic disease or disease-related symptoms, regression of enlarged lymph nodes or nodal masses to normal size, regression of previously enlarged spleen and other organs, and clear repeat bone marrow assessment. Partial response required a decrease of at least 50% in the sum of the products of diameters of the 6 largest dominant nodes or nodal masses, with additional requirements concerning other nodes, organs, and new disease sites. Participants with complete response but persistent morphologic bone marrow involvement, or without a post-treatment bone marrow assessment, were classified as partial responders.

A response percentage is used to express how many participants met the endpoint definition, while the 95% confidence interval describes uncertainty around that estimate. The primary response percentage and confidence interval are not reported in the registry record. The endpoint therefore cannot be interpreted quantitatively from the posted primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods can be understood by separating the endpoint’s definition, its summary measure, and the limits of the design. The primary endpoint is binary at the participant level: a participant either met the complete-or-partial-response definition or did not. The registry describes the result as a percentage of participants and specifies a 95% confidence interval. The response estimate and interval themselves are not reported in the registry record.

What does a confidence interval mean?

General statistical explanation: a confidence interval expresses uncertainty around an estimate. For a response percentage, the interval indicates the range of values compatible with the observed data under the method used to calculate it. A narrower interval generally reflects greater precision, while a wider interval reflects greater uncertainty. The interval does not replace the observed percentage, and it does not describe the range of individual participant outcomes. Since neither the percentage nor its 95% confidence interval is reported for the primary endpoint, the precision of this study’s response estimate cannot be assessed from the registry record.

What does a single-arm design allow?

General statistical explanation: a single-arm study estimates outcomes in the group that received the study regimen. It does not create a concurrent randomized comparison. Consequently, an outcome percentage can describe what happened in the enrolled group, but it cannot by itself estimate how outcomes would have differed under another treatment. Non-randomized allocation and no masking are recorded for this study; no control arm is listed. The registry does not report a statistical method that would turn the single-arm design into a controlled comparison.

How should the survival outcomes be understood?

The listed secondary outcomes include Kaplan-Meier estimates of progression-free survival at 6 months and 2 years, along with event-free survival after transplantation and overall survival. General statistical explanation: Kaplan-Meier methods estimate the proportion remaining free of an event over time while accounting for participants whose observed follow-up ends before the event is observed. Such estimates depend on the event definition, follow-up, censoring rules, and analysis population. The registry record names the progression-free survival time points but does not report the estimates, confidence intervals, event definitions, or censoring details needed to evaluate those analyses. The record also does not report numerical results for the other survival outcomes.

What can the planning illustration say?

The record describes sample-size figures as planning illustrations calculated from the observed effect, not as the trial’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations use total events, while other illustrations are expressed as participants per arm. These are planning assumptions, not evidence that the study randomized participants to two arms, and not observed power. The actual sample-size illustration values are not reported in the registry record. The effect estimate used for planning and any original sample-size justification are also not reported in the registry record.

General statistical explanation: a planning calculation asks how much information might be needed to detect a chosen effect under specified assumptions. It does not measure the probability that a completed study has proved a treatment effect, and it cannot substitute for the observed estimate and its uncertainty. An illustration based on an observed effect is also dependent on that effect estimate; it should not be mistaken for the study’s prospective design rationale.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a method ignores that extra variability, uncertainty may be understated and confidence intervals may be too narrow. For a participant-level response percentage, the relevant analysis depends on the endpoint structure and the chosen model. The registry record does not report an over-dispersion model or a need for one, so no claim can be made that this issue affected the study’s analysis.

The registry lists 0 analyses. This does not supply a detailed statistical analysis plan: specific estimation procedures, confidence-interval methods, model adjustments, interim analyses, and prespecified subgroup analyses are not reported in the registry record. Therefore, the named endpoints and general methods should not be read as a complete account of how every analysis was conducted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Rituximab 375 mg/m^2 + Inotuzumab Ozogamicin 1.8 m")
n      <- c(63)
events <- c(18)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Rituximab 375 mg/m^2 + Inotuzumab Ozogamicin 1.8 m  63  18  28.6  17.9  41.3  18.9  40.7  18.9  40.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary response endpoint and secondary response, survival, mobilization, and transplantation outcomes. Evaluating multiple outcomes creates a multiplicity question: when several statistical tests are conducted, the chance of at least one apparently notable result can rise. General statistical explanation: investigators may address this through prespecified testing sequences, adjustment procedures, or careful emphasis on a primary endpoint. The registry record does not report a multiplicity adjustment, testing hierarchy, or other plan for controlling the interpretation of multiple outcomes. It lists 0 analyses, which does not provide the missing methodological detail.

The primary endpoint population is intention-to-treat and is defined as all participants enrolled. The endpoint includes confirmed and unconfirmed complete or partial responses. These definitions clarify the intended population and response categories, but they do not explain how missing assessments, withdrawals, or participants without a post-treatment response classification were handled. Missing-data rules and the number of participants with missing endpoint data are not reported in the registry record.

Further analysis-population details are also not reported in the registry record. The record does not describe a per-protocol population, an evaluable-response population, or how participants were counted in each secondary outcome. In particular, the populations used for post-transplant outcomes may depend on who underwent transplantation; the record lists the outcome but does not provide the analysis denominator or an analysis-population definition for it.

Interim analyses, stopping rules, subgroup analyses, and protocol-based handling of missing information are not reported in the registry record. These omissions do not establish that such methods were absent; they mean that the registry information does not describe them. The primary response result is also not reported, limiting interpretation independently of these methodological gaps.

12. 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: thrombocytopenia (12.7%), febrile bone marrow aplasia (3.2%), febrile neutropenia (3.2%), neutropenia (3.2%), aplasia (3.2%).

The registry reports one treatment group with 63 participants at risk for serious adverse events and 29 participants affected. For other adverse events, it lists 63 at risk and 63 affected. These are separate event groupings and should not be added together: the record does not indicate that participants in the groupings are distinct. Nor does an affected-participant count describe how many events each participant experienced.

The listed serious adverse event terms and percentages are thrombocytopenia, 12.7%; febrile bone marrow aplasia, 3.2%; febrile neutropenia, 3.2%; neutropenia, 3.2%; aplasia, 3.2%; and nausea, 3.2%. The registry lists these as top serious terms. It does not report the full serious-event listing in the information available for this summary, nor does it provide details on event duration, recurrence, timing, or attribution. The percentages should be read as the registry’s reported figures, not as rates recalculated from the affected-participant count.

Deaths are not reported in the registry record. No comparison group is present, so these figures do not provide a comparative estimate of adverse event risk. General statistical explanation: adverse event counts describe events recorded under specified definitions and follow-up; they are not, by themselves, proof that a treatment caused an event.

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

The study’s primary question concerns the proportion of enrolled participants who achieved complete or partial response after 3 cycles of inotuzumab ozogamicin plus rituximab. The registry provides a detailed response definition, identifies the intention-to-treat population, and states that the endpoint includes confirmed and unconfirmed responses. However, the primary response percentage and its 95% confidence interval are not reported in the registry record. The magnitude and precision of the primary result therefore cannot be interpreted from the posted information.

Even if a response estimate were available, the single-arm, non-randomized design would support a description of outcomes within the treated group, not a randomized claim about relative benefit compared with another regimen. No comparator is listed. The design cannot separate a treatment-associated outcome from the effects of participant selection, disease course, other care, or other influences. The record does not provide evidence for causal attribution through a controlled contrast.

The secondary outcomes ask additional questions about progression-free survival, overall survival, stem-cell mobilization, transplantation, and outcomes after transplantation. These outcomes represent different clinical events and analysis timeframes. Their names in the registry do not show their results. Numerical results for these secondary outcomes are not reported in the registry record in the information.

The safety listing reports participant counts and selected serious adverse event terms. Those figures are useful descriptions of what the registry records, but they do not establish comparative safety, causal association, or the complete experience of every participant. Deaths are not reported in the registry record.

Accordingly, the study record supports statements about design, enrollment, the intended regimen, endpoint definitions, and selected safety counts. It does not support a numerical conclusion about the primary response result or a comparison with another treatment. A result not reported in the registry cannot be inferred from the study’s title, endpoint, completion status, or list of secondary outcomes.

14. Why This Trial Matters Statistically

This trial illustrates why study design and result reporting must be considered together. Its primary endpoint is a participant-level response percentage, and its clinical definition distinguishes complete from partial response using clinical, radiographic, organ, and bone marrow findings. That level of definition helps clarify what counts as an outcome. Yet the percentage and 95% confidence interval are not reported in the registry record, so the endpoint definition alone cannot tell readers how frequently the outcome occurred or how precise the estimate was.

The single-arm design makes the distinction between describing an outcome and estimating a comparative treatment effect especially important. A response percentage from one treatment group can describe that group, but without a randomized comparator it cannot isolate what would have happened under an alternative. This is a design limitation, not something that statistical interpretation of a response percentage can remove.

The record also places response alongside survival, mobilization, and transplantation outcomes. These represent different questions and may involve different participant populations and follow-up periods. Explicit outcome definitions, denominators, missing-data rules, and analysis methods are important for understanding how such results relate to the enrolled group. Several of those details are not reported in the registry record.

Finally, the record’s planning-illustration description is distinct from the original study design and from observed power. Planning assumptions can illustrate how a chosen effect relates to a hypothetical study size, but they do not replace reported outcome estimates. For this study, the primary result is not reported, and the original sample-size justification is not reported in the registry record. Keeping these distinctions clear prevents design descriptions, planned outcomes, and actual results from being conflated.

15. 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 for interpreting the posted results is that the primary response percentage and its 95% confidence interval are not reported in the registry record. The record therefore does not permit assessment of the response estimate’s magnitude or precision. Numerical results for the listed survival and other secondary outcomes are also not reported in the registry information used for this summary.

The single-arm, non-randomized design has no concurrent control group. As a result, observed outcomes among enrolled participants cannot be interpreted as a randomized treatment contrast. No masking was used, and the registry does not report how outcome assessment was organized or whether any independent review was conducted.

The endpoint definition is detailed, but the registry does not report the number of participants with missing response assessments or the rules used to handle missing data. Although the primary population is defined as all enrolled participants and responses include confirmed and unconfirmed categories, the record does not give counts for those categories or clarify the endpoint denominator used in the result calculation.

The registry lists several secondary outcomes, but it does not report a multiplicity plan, analysis hierarchy, or detailed analysis populations. Interim analyses, stopping rules, subgroup analyses, protocol deviations, and a full statistical analysis plan are not reported in the registry record. The original sample-size justification is also not reported. The serious adverse event record supplies group counts and selected terms, but deaths are not reported, and the information does not establish comparative safety or causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Evaluating Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Diffuse Large B-Cell Non-Hodgkin's Lymphoma — NCT00867087.
• Registry record last updated 2017-12-05; status last verified 2017-10.
• Results first posted 2017-08-22.
• 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.

19. Record Summary

The registry record describes a completed Phase 2, open-label, single-arm, non-randomized study of inotuzumab ozogamicin plus rituximab before autologous stem cell transplantation in relapsed or refractory diffuse large B-cell lymphoma. Enrollment was 64. The listed regimen was rituximab 375 mg/m^2 plus inotuzumab ozogamicin 1.8 mg/m^2.

The primary endpoint was the percentage achieving complete or partial response after 3 cycles, including confirmed and unconfirmed responses in the intention-to-treat population. Its response percentage and 95% confidence interval are not reported in the registry record. The registry lists 11 outcome measures and 0 analyses.

For the treatment group, the record lists 63 participants at risk and 29 affected for serious adverse events, and 63 at risk and 63 affected for other adverse events. Deaths are not reported in the registry record. Because the study has no comparator, the recorded outcomes are descriptive rather than randomized comparisons.