A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL (NCT00858117), a na phase 2 study. The primary outcome is Number of Patients Treated With Alemtuzumab and Rituximab Combination With a Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Lymph-adenopathy and Organomegaly Measured During Physical Examination.

2. Clinical Question

The clinical question is therefore a within-group question about response and safety during treatment with the combination. It is not a direct comparison of alemtuzumab plus rituximab against either drug alone, another regimen, or a control condition. Without a separate comparator, differences attributable to the combination cannot be separated from other explanations through a randomized contrast.

The registry gives the response assessment schedule as week 9, then after 18 weeks, followed by assessments every 3 months for a year and every 6 months for up to 2 years. That schedule describes when the endpoint was intended to be assessed; it does not establish how many participants completed each assessment or when any reported response occurred. Those details are not reported in the registry record.

3. Trial Design

This is a Phase II study sponsored by Northwestern University. Its design is listed as single-group, with allocation not applicable and no masking. The registry records enrollment of 30 participants and a completed status. The recorded start date is 2005-09-26, and the primary completion date is 2010-03-17. These dates describe the registry record; they do not establish the duration of treatment or follow-up for an individual participant.

The sole listed group received alemtuzumab and rituximab. The arm description states that the combination was being tested for feasibility as first-line therapy in patients with B-cell CLL. Since the study has no separate comparison group, the design can describe outcomes among participants in the group, but it does not provide a randomized estimate of how those outcomes differ from outcomes under another treatment.

The primary outcome is a count of participants with a complete or partial response under NCI-WG 1996 criteria. The registry description includes physical examination for lymphadenopathy and organomegaly, as well as blood and marrow criteria. The specified assessment schedule begins at week 9 and continues at stated intervals. A response count or an analysis of the primary endpoint is not reported in the registry record.

A secondary outcome is toxicity of the study medications. The record includes adverse-event counts for the treatment group, including counts for serious and other adverse events, and lists serious-event terms. These safety data should be read as descriptive registry counts rather than as a comparison between treatment groups.

The registry lists 5 outcome measures and 0 analyses. It does not report a detailed statistical analysis plan, a sample-size justification, interim analyses, or details of analysis populations. The absence of those details means the intended analysis procedures cannot be reconstructed from this record. The completed status and enrollment count alone do not indicate whether all enrolled participants contributed to each outcome.

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.

Treatment on Study

Reasons for not completing this period:

Follow up for 5 Years

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 Number of Patients Treated With Alemtuzumab and Rituximab Combination With a Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Lymph-adenopathy and Organomegaly Measured During Physical Examination, measured over At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years.

The primary endpoint counts participants whose best recorded response met the registry’s definition of complete remission (CR) or partial remission (PR). The response rate is described as CR plus PR, with assessment according to NCI-WG 1996 criteria. The record specifies examination of lymphadenopathy and organomegaly and also includes blood-count and, for CR, marrow criteria. These criteria make the endpoint a clinical response classification rather than a direct count of cancer cells alone.

For CR, the description includes absence of lymphadenopathy and constitutional symptoms, specified blood-count thresholds, a peripheral blood lymphocyte threshold, and a marrow requirement. For PR, it includes absence of constitutional symptoms, reductions in peripheral blood lymphocyte count, lymphadenopathy, and liver and/or spleen size, together with specified blood-count improvement criteria. The registry spells out these thresholds, including leukocytes ≥ 1500/μl, platelets >100,000/μl, hemoglobin > 11.0 gm/dl, and peripheral blood lymphocytes ≤ 4,000/μl for elements of the CR definition. The PR definition includes the stated reductions and thresholds.

General statistical context: a response endpoint can provide a clinically interpretable summary of whether participants met a prespecified category at assessment. Combining CR and PR into one endpoint counts either category as a response, but it does not show the separate number in each category unless those counts are reported. The primary response count and its analysis are not reported in the registry record, so the endpoint definition alone does not establish how many participants responded.

The assessment schedule is recorded as at week 9, after 18 weeks, then every 3 months for a year and every 6 months for up to 2 years. The record does not state which assessment was used to classify each participant’s response, nor does it report completeness of endpoint assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a single-group Phase II design. This is important because the study has no separate randomized comparator. Its primary endpoint is a participant count: the number meeting the complete or partial response definition. The record lists 0 analyses, so the statistical analysis procedures used for the primary endpoint are not reported in the registry record.

What does a single-group design estimate?

General statistical context: a single-group study can describe outcomes observed among participants who received a regimen. For a binary outcome such as response, the basic descriptive result is the number classified as having the outcome, often considered alongside the number assessed. If an analysis reports a proportion, its interpretation depends on the denominator and how missing or unevaluable outcomes were handled. Those primary endpoint counts and handling details are not reported in the registry record.

A single-group result is not a treatment contrast. Without a comparator group, it is not possible to estimate from this design alone how response or adverse events would differ under another treatment. Participants’ outcomes may also reflect characteristics of the enrolled group, the natural course of disease, other care, and measurement or follow-up practices. These are general limitations of interpreting uncontrolled results, not additional findings about this trial.

Why does a confidence interval matter?

General statistical context: a confidence interval communicates the uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither width nor statistical significance resolves design limitations such as the absence of a control group. The registry does not report a confidence interval or an analyzed response estimate, so precision for the primary endpoint cannot be assessed from the record.

A confidence interval would also need a clearly defined analysis population and denominator to be interpretable. For this trial, enrollment is recorded as 30, but the record does not state how many participants were included in the primary endpoint analysis or how incomplete assessments were treated. Enrollment should not automatically be treated as the number analyzed.

What does the endpoint definition contribute?

The endpoint uses NCI-WG 1996 response criteria, combining complete and partial responses. The criteria specify clinical examination findings and blood and marrow measures. Such criteria aim to apply a consistent classification rule across participants. General statistical context: standardized criteria can reduce ambiguity in outcome classification, but they do not eliminate measurement variation or missing assessments. The registry does not report assessor procedures, blinding, adjudication, or the handling of participants who could not be classified.

The assessment schedule is recorded as at week 9, after 18 weeks, then every 3 months for a year and every 6 months for up to 2 years. General statistical context: repeated assessments can yield different response classifications over time. An analysis therefore needs to specify whether it uses a particular time point, best response, or another rule. The registry describes the schedule and a response endpoint, but does not report the analysis rule linking multiple assessments to the final endpoint count.

How should the safety counts be read?

General statistical context: adverse-event counts are descriptive unless a defined comparison and analysis support a comparative interpretation. A participant may experience more than one event, so counts of event terms do not necessarily equal counts of unique participants. A serious-event count, a count affected by other events, and a death count describe different registry categories and should not be combined or treated as interchangeable. The record does not report whether event categories overlap, nor does it report treatment-relatedness assessments or event timing.

Over-dispersion is a general issue in count-data analyses when variability exceeds what a chosen statistical model expects. It can affect standard errors and confidence intervals if a model assumes less variability than the data contain. The posted primary endpoint is described as a count of participants with an event, not as a reported modeled count analysis. No model, dispersion estimate, or count-analysis result is reported in the registry record; over-dispersion therefore cannot be evaluated as a feature of the posted primary analysis.

What do planning illustrations mean?

General statistical context: a sample-size planning illustration asks how many participants might be needed under stated assumptions to detect an effect at a chosen significance level and power. It is a prospective planning calculation, not an observed outcome and not evidence that a study had a particular probability of success. The registry record does not report the trial’s own sample-size justification. The stated illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect; these are not described as the trial’s actual design.

The record states that non-time-to-event illustrations express participants per arm, while time-to-event illustrations express a total number of events. Since this study is single-group, an equal-allocation two-arm illustration does not describe the actual trial design. No planning estimate should be read as observed power or as evidence about the trial’s response result.

In short, statistical methods can explain what a response count, uncertainty interval, or planning illustration would mean in general. The registry does not report the primary response count, its analysis, its precision, or the detailed rules needed to reconstruct those analyses. The design and endpoint definition are reported; the inferential results are not.

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("Alemtuzumab and Rituximab")
n      <- c(30)
events <- c(30)
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  Alemtuzumab and Rituximab  30  30  100.0  88.4  100.0  88.6  100.0  88.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and identifies response as the primary endpoint, with toxicity as a secondary outcome. It reports 0 analyses. The statistical plan, including any procedures for handling multiple outcomes or repeated assessments, is not reported in the registry record. It is therefore not possible to determine whether multiplicity was addressed through a prespecified hierarchy, adjustment, or another method.

General statistical context: testing or estimating multiple outcomes can increase the chance of at least one apparently notable result when each is interpreted independently. A prespecified primary endpoint can help focus interpretation, but readers still need the analysis plan to understand how secondary outcomes and repeated measurements were treated. The registry describes scheduled response assessments at week 9, after 18 weeks, and at later intervals, but does not specify which assessment or summary rule determined the primary response classification.

Missing data are also not described for the primary endpoint. The record does not report the number of participants with an evaluable response, reasons for missing assessments, or whether missing outcomes were excluded, imputed, or handled under another rule. General statistical context: the way missing observations are handled can affect both the estimated outcome and its uncertainty, particularly when missingness is related to health status or response. Without these details, the denominator and potential influence of incomplete assessment cannot be evaluated.

The analysis populations are not reported in the registry record. It is not stated whether the primary endpoint was assessed in all enrolled participants, only participants who began treatment, or another defined group. Enrollment of 30 should not be assumed to be the endpoint analysis denominator. The record also does not report a detailed statistical analysis plan or interim analyses. No conclusion about those procedures can be drawn from the completed status or the listed outcomes.

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: diffuse large b cell lymphoma (10.0%), possible infection with fever (6.7%), chronic myelogenous leukemia (3.3%), multiple myeoma (3.3%), urachal adenocarcinoma of the bladder (3.3%).

The registry lists one treatment group, Alemtuzumab and Rituximab, with 30 participants at risk for other adverse events and 30 affected. For serious adverse events, 30 are listed as at risk and 11 as affected. The record also lists 4 deaths. These are registry counts, and the record does not provide enough detail to determine whether event categories overlap, how events were attributed, or whether deaths were related to treatment.

The listed serious-event terms and percentages are diffuse large B cell lymphoma (10.0%), possible infection with fever (6.7%), chronic myelogenous leukemia (3.3%), multiple myeoma (3.3%), urachal adenocarcinoma of the bladder (3.3%), and esophageal cancer (3.3%). The terms and percentages describe what the registry lists; they do not establish causation or provide a comparison with another group.

General statistical context: safety counts are easier to interpret when the event definition, observation period, number assessed, and treatment-relatedness rules are clear. The registry record does not report those details. Event-term percentages should not be combined or added, since the record does not state whether participants could contribute to more than one term. The figures are descriptive records, not comparative risk estimates.

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

The record establishes that a Phase II, single-group trial evaluated alemtuzumab combined with rituximab in previously untreated B-cell CLL. It gives an enrollment of 30, describes a complete-or-partial-response endpoint, and records safety counts and serious-event terms. These registry entries characterize the study question and the information posted about its outcomes.

The primary response result is not reported in the registry record. Although the endpoint definition and assessment schedule are described, the record does not state how many participants had a complete or partial response, how many had each response category, or how precise any response estimate was. A defined endpoint is not itself an outcome result. Without the count and an analysis denominator, the primary endpoint cannot be quantitatively interpreted.

The single-group design also limits what the study can establish. General statistical context: observations in one treatment group can describe that group, but they cannot provide a randomized comparison with an alternative. The registry does not support attributing outcomes to the combination in a comparative sense. The posted safety counts likewise do not establish that the listed events were caused by treatment, and the death count does not establish treatment relatedness.

The record does not report the analysis population, handling of missing outcomes, detailed statistical plan, or primary endpoint analysis. These omissions mean that even a reader familiar with the endpoint criteria cannot reconstruct the intended inferential analysis or assess whether all enrolled participants contributed to it. The completed status and the enrollment count do not resolve those gaps.

Thus, the record supports a description of the trial design, intended response assessment, and posted safety information. It does not provide a numerical response finding or a comparative estimate of treatment effect. General statistical context can clarify why a comparator, denominator, and uncertainty estimate matter, but those concepts cannot substitute for results absent from the registry record.

14. Why This Trial Matters Statistically

This trial illustrates a basic distinction between defining an outcome and reporting its result. The registry gives a detailed response definition based on NCI-WG 1996 criteria and an assessment schedule, but does not report the number of participants with a response or an analysis of that endpoint. Readers therefore cannot infer the observed response from the endpoint description alone.

It also illustrates the interpretive limits of a single-group design. A response or safety count in one group describes that group, but does not estimate how outcomes compare with another treatment. This distinction matters when a study’s purpose includes assessing how well a regimen works: a within-group outcome and a comparative treatment effect are different statistical questions.

The safety record makes another important distinction visible: counts of participants affected, serious-event terms, and deaths are not interchangeable measures. The record identifies 11 participants affected by serious adverse events and 30 affected by other adverse events, with 4 deaths, but does not report relatedness, timing, overlap, or comparative safety. A careful reading preserves those categories and avoids attributing cause where the record does not establish it.

General statistical context: transparent reporting of denominators, analysis populations, missing-data handling, and uncertainty allows readers to judge how much confidence to place in an estimate. Here, the registry lists 5 outcome measures and 0 analyses, while the primary result and detailed analysis procedures are not reported in the registry record. The resulting lesson is methodological rather than clinical: trial design, endpoint definition, and outcome reporting each answer different questions, and none can stand in for the others.

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 direct limitation is that the primary endpoint result is not reported in the registry record. The number of participants with a complete or partial response, the denominator used for analysis, and any estimate of uncertainty are absent. The endpoint definition and assessment schedule do not supply those missing results.

The study is single-group, with no listed comparator. This prevents a direct randomized comparison with another regimen or control condition. Any description of outcomes among the enrolled participants would not, by itself, establish how outcomes differ under another treatment. Allocation is listed as not applicable and masking as none.

Important analysis details are not reported in the registry record. These include the statistical analysis plan, analysis populations, handling of missing or unevaluable response assessments, the rule for summarizing repeated assessments, and interim analyses. The record lists 5 outcome measures and 0 analyses, so the intended analytic treatment of multiple outcomes is also unclear.

The safety information is limited to registry counts and listed serious-event terms and percentages. The record does not report event timing, treatment-relatedness assessment, participant-level overlap, or the circumstances of the 4 deaths. The counts should therefore be treated as descriptive rather than causal or comparative.

The sample-size justification for the trial is not reported in the registry record. The stated planning-illustration assumptions are not the trial’s own design, and no conclusion about observed power can be drawn from them. Finally, enrollment of 30 does not establish that all participants had complete follow-up or contributed to every endpoint. The record does not provide those completion details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL — NCT00858117.
• Registry record last updated 2020-11-06; status last verified 2020-10.
• Results first posted 2020-10-19.
• 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

This registry record describes a completed Phase II, single-group study sponsored by Northwestern University. It lists enrollment of 30 participants with previously untreated B-cell CLL and a treatment group receiving alemtuzumab combined with rituximab. The primary endpoint is a count of participants with a complete or partial response under NCI-WG 1996 criteria. Assessments were scheduled at week 9, after 18 weeks, and at later stated intervals.

The registry lists 5 outcome measures and 0 analyses. The primary response count and its analysis are not reported in the registry record. Safety information includes 11 participants affected by serious adverse events, 30 affected by other adverse events, and 4 deaths. Serious-event terms and percentages are listed, but the record does not establish event relatedness or provide a comparator.

The single-group design supports descriptive interpretation only; it does not provide a randomized treatment comparison. The registry also does not report the detailed statistical plan, analysis populations, or missing-data procedures.