CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies (NCT01664910), a na phase 1, phase 2 study. The primary outcome is Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT.

2. Clinical Question

In statistical terms, the study’s central question is dose-focused: how many participants in each dose cohort received inotuzumab without a DLT during the recorded observation window? This differs from a comparative question about whether a treatment improves an outcome relative to another treatment. With a single group, the record can describe outcomes among participants who received the regimen, but it cannot by itself establish how those outcomes compare with what would have happened under a different regimen.

Overall response and overall survival are listed as secondary outcomes. Their results are not reported in the registry record. The available information therefore does not answer whether response or survival differed across dose cohorts, nor whether any observed outcome was attributable to one component of the treatment rather than the combined regimen and transplantation.

3. Trial Design

The study is listed as phase I/II, completed, and single-group, with enrollment of 27. The sponsor is M.D. Anderson Cancer Center. Masking is listed as none, and allocation is not applicable. These features describe a trial without a randomized control group and without masking as recorded in the registry.

The intervention combined inotuzumab ozogamicin with fludarabine and bendamustine before allogeneic transplantation; rituximab is included for patients with CD20-positive disease in the treatment description. The registry also lists transplant procedures and agents including anti-thymocyte globulin and methotrexate. The treatment description is not complete enough in the registry record to reconstruct every aspect of the regimen or its administration.

The safety record is organized into three dose cohorts: 0.6 mg/m2, 1.2 mg/m2 and 1.8 mg/m2 of inotuzumab ozogamicin. The adverse-event entries list 4, 2 and 21 participants at risk in those cohorts, respectively. These are cohort-specific safety denominators; they should not be treated as evidence of randomized groups or as a control comparison. The registry record does not explain the cohort allocation process or provide the decision rules used to move between doses.

The primary endpoint is a count of participants in each cohort who received inotuzumab without DLT, with a timeframe of up to 30 days. Overall response and overall survival are listed as secondary outcomes. Although the trial is marked completed, the primary and secondary outcome results are not reported in the registry record. The record also does not report a statistical analysis plan, sample-size justification, or interim-analysis plan.

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:

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 Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT, measured over Up to 30 days.

The primary endpoint is described as the maximum-tolerated dose of inotuzumab without DLT. Its measure is a count: the number of participants in each cohort who received inotuzumab without dose-limiting toxicity during a timeframe of up to 30 days. The endpoint is therefore focused on tolerability during the recorded period, rather than on a continuous measurement or a comparison of treatment effects between randomized groups.

In general, dose-finding studies use observed toxicity at different dose levels to inform whether a dose is tolerable enough to consider for further study. The endpoint’s usefulness depends on how DLT is defined, which participants are considered evaluable, how the observation window is applied, and what decision rule is used to identify the maximum tolerated dose. Those criteria and rules are not reported in the registry record. The record also does not report the count for any cohort or identify a maximum-tolerated dose result.

A count should be interpreted alongside the number of participants assessed in its cohort and the endpoint definition. The safety entries give cohort-specific participants at risk, but do not establish that these are necessarily the exact analysis denominators for the primary endpoint. Without the primary endpoint results and the analysis population definition, the endpoint cannot be independently interpreted as evidence for a particular dose.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group trial and a primary endpoint expressed as a participant count. It does not report the statistical methods used to analyze that endpoint or the secondary outcomes. The concepts below explain how such information is generally interpreted; they are not claims about methods used in this trial.

What does a participant count convey?

A count records how many participants meet a defined event criterion. For the primary endpoint, that criterion is receiving inotuzumab without DLT during a timeframe of up to 30 days. A count alone is incomplete: interpretation also depends on the number of participants eligible for evaluation, the operational definition of DLT, and how incomplete follow-up or missing assessments are handled. The registry’s safety entries provide participants at risk by cohort, but the primary endpoint’s analysis denominators and counts are not reported.

In general, a proportion can be estimated by relating an event count to its relevant denominator. Uncertainty around a proportion reflects the amount of information in the observed data and the variability expected from sampling. A confidence interval is a range of estimates compatible with the data and a specified statistical procedure; wider intervals indicate less precision. No primary endpoint proportions or confidence intervals are reported in the registry record, so the precision of the dose-specific endpoint cannot be assessed from the record.

How should dose cohorts be viewed?

Dose cohorts describe participants treated at different dose levels. In general, dose-finding decisions may use the observed pattern of toxicity across doses, but the interpretation depends on the trial’s assignment and escalation rules. The registry record lists cohorts at 0.6 mg/m2, 1.2 mg/m2 and 1.8 mg/m2, but does not report the rules governing assignment, escalation, stopping, or selection of the maximum-tolerated dose. A reader should not infer a dose-selection algorithm from the dose labels alone.

Comparing cohort counts as if the groups were randomized would be inappropriate without evidence that the design supported that comparison. Cohort size, participant characteristics, follow-up, and treatment exposure can differ, and such differences can influence observed event counts. General statistical adjustment can address only measured factors and depends on suitable data and a prespecified model; the registry record reports no adjusted analysis. The study’s single-group structure also means there is no separate control group for estimating a treatment contrast.

What do confidence intervals and p-values add?

In general, a confidence interval communicates uncertainty around an estimate, while a p-value assesses how compatible the observed data are with a specified null hypothesis under a statistical model. Neither measure establishes clinical importance or removes bias from study design. Results should be interpreted with the estimate, its uncertainty, the analysis population, and the design in view. The registry record does not report p-values or confidence intervals for the listed outcomes, nor does it describe hypotheses or statistical models.

How do the planning illustrations differ from trial results?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are described as using a stated fraction of an observed effect. For time-to-event planning, the illustration is based on a total event count; other planning illustrations are expressed as participants per arm. These are planning assumptions, not observed trial findings and not observed power.

Those assumptions do not describe this trial’s single-group design. The record explicitly identifies the study as not being a randomized comparison, so a two-arm, equal-allocation planning scenario should not be mistaken for the trial’s enrollment plan or actual analysis. The registry record does not report the trial’s own sample-size justification. A planning illustration cannot fill that gap or establish whether the study had adequate precision for its primary endpoint.

Why does over-dispersion matter in general?

For count outcomes, some statistical models assume that variability follows a particular relationship to the average count. Over-dispersion occurs when the observed variability is greater than that assumption allows. If a model ignores over-dispersion, standard errors may be too small and intervals or tests may give a misleading impression of precision. This is a general consideration for count-data modeling; the primary endpoint is a count of participants meeting a binary criterion, and the registry record does not report a model or a check for over-dispersion.

Overall survival is a time-to-event outcome in general: the analysis concerns the time until an event, while accounting for participants whose event status is not observed over the full period. Such analyses commonly require stated definitions of the event, censoring rules, and analysis methods. The registry record names overall survival but does not report those details or its results. No particular survival method should therefore be attributed to this trial.

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("Cohort 1:Allogeneic TP for CD22(+) Lymphoid Malign", "Cohort 2:Allogeneic TP for CD22(+) Lymphoid Malign", "Cohort 3:Allogeneic TP for CD22(+) Lymphoid Malign")
n      <- c(4, 2, 21)
events <- c(4, 2, 20)
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  Cohort 1:Allogeneic TP for CD22(+) Lymphoid Malign  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  Cohort 2:Allogeneic TP for CD22(+) Lymphoid Malign  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 3:Allogeneic TP for CD22(+) Lymphoid Malign  21  20  95.2  76.2  99.9  77.3  99.2  77.2  98.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and two secondary outcomes: overall response and overall survival. Testing or estimating several outcomes can raise a multiplicity issue. In general, when multiple hypotheses are assessed, the chance of obtaining at least one apparently notable result can increase unless the analysis plan addresses that issue. A prespecified hierarchy, adjustment procedure, or clearly descriptive interpretation can help explain how multiple outcomes should be read. The registry record does not report a multiplicity strategy, and it does not provide outcome analyses from which to assess how this issue was handled.

Missing-data methods and analysis populations are also not reported in the registry record. It does not specify how participants with incomplete DLT observation, missing outcome assessments, or incomplete follow-up were treated. The primary endpoint is framed as a count of participants without DLT, but the record does not state who was eligible for that count or how missing assessments affected the denominator. A count of participants at risk in a safety cohort should not automatically be assumed to define the primary endpoint analysis population.

The record does not describe an intention-to-treat population, a safety population, or another analysis set for the listed outcomes. Nor does it report imputation procedures, censoring rules for overall survival, or sensitivity analyses for missing data. These omissions limit the ability to reproduce or evaluate an analysis even if the outcome values were available. Because the endpoint results themselves are not reported, the registry record does not allow assessment of how missingness or multiplicity may have affected the findings.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bacterial (9.5%), dah (9.5%), gi gvhd (9.5%), encephalopathy (4.8%), hsct related microangiopathy (ta-tma) (4.8%).

The adverse-event entries report participants at risk, participants affected by serious adverse events, participants affected by other adverse events, and deaths for each cohort. In the 0.6 mg/m2 cohort, the record lists 4 at risk, 0 with serious adverse events, 4 with other adverse events, and 0 deaths. In the 1.2 mg/m2 cohort, it lists 2 at risk, 0 with serious adverse events, 2 with other adverse events, and 0 deaths. In the 1.8 mg/m2 cohort, it lists 21 at risk, 2 with serious adverse events, 16 with other adverse events, and 7 deaths.

These are descriptive registry counts. The serious and other adverse-event categories are distinct reported summaries; a participant count does not indicate how many events occurred, whether events recurred, or how severe each event was. The record does not report the attribution of events to treatment, their timing, or the follow-up period used for these safety summaries. The listed deaths should not be assumed to have been caused by treatment.

The registry also lists Bacterial, DAH and GI GvHD at 9.5%, and Encephalopathy, HSCT related microangiopathy (TA-TMA) and Chronic GI GvHD at 4.8%. These are reported term percentages. The record does not identify the denominator or provide enough detail to interpret these terms as comparative risks. Because the cohorts are not randomized comparison groups, the counts do not establish that one dose caused more or fewer events than another.

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

The record describes a completed phase I/II, single-group study of inotuzumab ozogamicin with other treatment before allogeneic transplantation for CD22-positive lymphoid malignancies. It identifies a primary endpoint focused on participants who received inotuzumab without DLT and lists overall response and overall survival as secondary outcomes. It also reports cohort-level safety counts and selected serious adverse-event terms.

These details do not establish that the regimen improves an outcome or is safer than another approach. There is no randomized comparator in the record, and the primary and secondary outcome results are not reported. The registry information therefore cannot show the size or precision of a treatment effect, establish whether a maximum-tolerated dose was identified, or support a causal comparison between dose cohorts.

The safety counts are useful as descriptive entries but have important limits. They do not by themselves explain event timing, duration, severity grading, attribution, or the relationship between an event and a treatment component. The record does not provide a complete analysis population definition or the follow-up details needed to interpret the counts as rates over a consistent period.

In general, an absence of a reported result is not evidence that an outcome did not occur. It means the registry record does not provide that result for interpretation. Likewise, a listed event count is not a comparative estimate and should not be taken as proof that an intervention caused or prevented an event. The available information is best read as a description of the trial framework and the safety summaries entered in the registry, not as a basis for a treatment recommendation or a conclusion about efficacy.

14. Why This Trial Matters Statistically

This trial illustrates why a dose-focused endpoint and a comparative treatment endpoint answer different statistical questions. Counting participants without DLT in each cohort is intended to describe tolerability in relation to dose. It does not, by itself, estimate the effect of the regimen relative to a control treatment. Recognizing that distinction prevents descriptive cohort results from being interpreted as if they came from a randomized comparison.

The regimen also combines several treatment components with transplantation. In general, when interventions are delivered together, attributing an observed outcome to one component requires a design and analysis capable of separating their effects. The registry record does not describe such a component-specific comparison. That is particularly relevant when considering outcomes such as overall response or overall survival, which are listed but whose results are not reported.

Another statistical lesson is that a named endpoint is not enough to evaluate a trial’s findings. Interpretation requires the endpoint result, its denominator, the analysis population, a clear definition of DLT, and a description of how uncertainty and missing observations were handled. The registry record does not report those details for the primary endpoint. It also does not report a statistical analysis plan or sample-size justification.

The safety entries show why counts should be read with their cohort context and limitations in mind. Cohorts have different reported sizes, and the design does not establish them as comparable control groups. The counts can describe what the registry records for each cohort, but they cannot alone establish a dose-related difference. The trial therefore provides a useful example of how registry design labels, endpoint definitions, and missing analysis details shape what can be concluded statistically.

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 primary limitation for interpretation is that the registry record does not report the primary endpoint result. It names the maximum-tolerated-dose endpoint and its timeframe, but gives neither the cohort counts without DLT nor the conclusion about dose selection. The DLT definition, evaluation criteria, and decision rules are also not reported, which prevents an independent assessment of how the primary endpoint was determined.

The trial is listed as single-group, with allocation not applicable and no masking. It therefore does not provide a randomized control comparison. The registry record does not explain how participants entered the dose cohorts or whether cohort characteristics differed. The cohort safety counts should not be treated as direct comparative evidence.

The safety record gives counts and selected event terms, but not details on timing, severity grading, attribution, recurrence, or the follow-up window for the safety summaries. The record also does not establish that participants at risk in the safety entries are the same population used for every outcome analysis. These limitations make it difficult to interpret the counts beyond their descriptive meaning.

Overall response and overall survival are listed as secondary outcomes, but their results and analysis methods are not reported. Statistical methods, missing-data handling, analysis populations, multiplicity procedures, sample-size justification, and interim-analysis plans are also not reported in the registry record. The treatment description is incomplete, limiting the ability to reconstruct the full regimen from the record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies — NCT01664910.
• Registry record last updated 2024-07-23; status last verified 2024-06.
• Results first posted 2024-07-23.
• 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 NCT01664910, a completed phase I/II, single-group trial sponsored by M.D. Anderson Cancer Center. Enrollment is listed as 27. The study evaluated inotuzumab ozogamicin with fludarabine, bendamustine and rituximab before allogeneic transplantation for CD22-positive lymphoid malignancies.

The primary endpoint is the count of participants in each cohort who received inotuzumab without DLT during a timeframe of up to 30 days. Dose cohorts are listed at 0.6 mg/m2, 1.2 mg/m2 and 1.8 mg/m2. Overall response and overall survival are listed as secondary outcomes.

Outcome results and statistical analysis methods are not reported in the registry record. Safety entries provide cohort-level counts and selected serious-event terms, but do not provide the detail needed for a comparative safety assessment. The single-group design does not establish a randomized control comparison.