Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL) (NCT01191190), a na phase 2 study. The primary outcome is IwCLL-WG Defined Complete Response (CR).

2. Clinical Question

This is a question about response observed in a treated group, not a comparison of the combination with another treatment or with no treatment. The registry record identifies complete response as the primary endpoint. It also lists overall response, nodular partial response, partial response, stable disease, progressive disease, progression-free survival, treatment-free survival, and safety and tolerability among the secondary outcomes.

The primary endpoint is defined by clinical and laboratory criteria, including blood counts, physical examination, and bone marrow assessment. The registry record states that a bone marrow biopsy and repeat CT scan were used to confirm complete response; the scan was specified for abdominal, chest, and pelvis sites if the initial scan was abnormal. The record does not report how many participants met the complete-response definition. As a result, the clinical question is clear, but its answer cannot be recovered from the posted primary endpoint information.

3. Trial Design

This was a phase II, completed, single-group study of ofatumumab in combination with high-dose methylprednisolone in people with relapsed or refractory chronic lymphocytic leukemia. The registry record lists enrollment of 21. Its recorded start was 2010-08, and primary completion was 2012-02. The sponsor is listed as Januario Castro, M.D.

The study has no concurrent control arm: allocation is listed as NA, masking as none, and the model as single group. Therefore, the design can describe what happened among participants receiving the regimen, but it cannot directly estimate how their outcomes differed from outcomes under another treatment. A response observed in a single group cannot by itself separate treatment effects from the course of illness, participant characteristics, or other influences.

The brief summary says participants would receive three consecutive 4 week cycles. HDMP is described as 1gm/m2 daily by infusion for 3 consecutive days every cycle. Ofatumumab is described as 300mg on Day 1 of cycle 1, followed by 12 doses of 1000mg. The arm description is truncated after stating that each patient may receive 3 cycles in the absence of progressive disease or another condition beginning with “si”; the remainder of that sentence is not reported in the registry record. The timing between the later ofatumumab doses is not reported in the registry record.

The primary endpoint was iwCLL-WG defined complete response, assessed two months after completion of therapy. The stated assessment included a bone marrow biopsy and repeat CT scan to confirm complete response, with the scan specified if the initial scan was abnormal. The registry record lists ten outcome measures and identifies several secondary outcomes, including response categories, survival outcomes, and safety. It does not report a statistical analysis plan, an analysis population, or the results for the primary endpoint.

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 IwCLL-WG Defined Complete Response (CR), measured over 2 months.

The primary endpoint is the number of participants with an iwCLL-WG defined complete response. It is a binary outcome at the participant level: each assessed participant either meets the complete-response definition or does not. The registry record sets the assessment time at two months after completion of therapy and describes confirmation using bone marrow biopsy and repeat CT scan, with imaging specified when the initial scan was abnormal.

The definition requires more than a change in one symptom or one laboratory value. It includes peripheral blood lymphocytes below 4 x 109/L (4000/L), absence of lymphadenopathy greater than 1.5 cm on physical examination, no hepatomegaly or splenomegaly on physical examination, and absence of constitutional symptoms. It also requires a normal complete blood count, including neutrophils ≥ 1,500/μl, platelets > 100,000/μl, non-transfused hemoglobin > 11.0g/dL, and lymphocyte count < 5,000/μl. The bone marrow must be normocellular for age, with <30% of nucleated cells being lymphocytes and no lymphoid nodules.

General statistical context: a complete-response endpoint turns a multidimensional clinical assessment into a clearly defined category at a specified time. This can make the outcome interpretable, but the count alone does not show how many participants were assessed or whether any were missing an assessment. The registry record does not report the observed complete-response count, so it does not establish the proportion meeting the definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome specified as primary is a participant count: the number meeting the iwCLL-WG complete-response definition at the stated assessment. For a binary outcome, each participant’s status is classified into one of two categories—meeting the definition or not meeting it. A response proportion can be estimated by relating the number meeting the definition to the number assessed, but neither the primary response count nor the number assessed is reported in the registry record. No such proportion can therefore be stated.

What does a confidence interval communicate?

General statistical explanation: a confidence interval describes uncertainty around an estimate, using a method with stated assumptions. For a binary response outcome, it can show how much uncertainty remains around an estimated response proportion. A narrow interval indicates greater precision than a wide interval, but the interval does not remove possible bias from study design, outcome assessment, missing observations, or differences between the participants studied and other populations. The registry record does not report a confidence interval for complete response, nor does it report a response estimate from which one could be interpreted.

The sample size is recorded as 21 enrolled participants. Enrollment is not automatically the denominator for every endpoint: some participants may not have an assessment recorded or may not meet the analysis population definition. The registry record does not report the number assessed for complete response, any exclusions, or how unavailable assessments were handled. It is therefore not appropriate to treat enrollment as the endpoint denominator without further information.

Why does the single-group structure matter?

General statistical explanation: a control group provides a contemporaneous reference for understanding differences in outcome under alternative conditions. In a single-group study, the observed outcome is described within the treated group. It does not estimate a treatment contrast, because there is no separate group assigned to a comparator. Here, the registry record specifies a single-group model, allocation NA, and no masking. It does not describe random allocation or a control arm. A response count, if reported, would therefore be an observed group result rather than a randomized comparison.

Masking can reduce the influence of knowledge of treatment assignment on some assessments, but this record lists masking as none. The primary endpoint includes objective laboratory and marrow criteria as well as physical findings and symptoms. The registry record does not describe procedures used to standardize assessment or to reduce assessment bias. This does not establish that bias occurred; it identifies information that is not reported in the registry record.

What can be inferred from the safety counts?

The safety information distinguishes participants affected by serious adverse events from those affected by other adverse events. For the Ofatumumab/HDMP group, 21 participants were at risk in each category. The record reports zero affected by serious adverse events and 21 affected by other adverse events. These are participant counts, not a complete listing of event types or timing. General statistical explanation: a count of participants with at least one event differs from a count of all events, because one participant may experience more than one event. The registry record does not give the serious adverse-event terms or a detailed event-level account.

The record’s death field has no numeric result. It should not be interpreted as a reported zero. A blank or unreported value is not evidence that no deaths occurred; it means the death count is not reported in the registry record.

What analysis plan is documented?

The registry record lists no analyses and does not report the statistical methods used to analyze the primary endpoint. It does not state whether an interval estimate was planned, what analysis population was intended, how missing assessments would be treated, or whether any adjustment was planned. General statistical explanation: an analysis plan matters because the choice of denominator, missing-data handling, and estimation method can affect the interpretation of a response result. Those choices cannot be reconstructed from the endpoint definition alone.

The record’s sample-size assumptions describe planning illustrations as based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; time-to-event illustrations are described in terms of total events, while other illustrations are described in participants per arm. These are planning assumptions, not a reported design justification or evidence of achieved power. They also do not turn this single-group study into a two-arm comparison. A sample-size illustration is not an observed trial result and cannot replace the missing complete-response count.

General statistical explanation: power is a design property under specified assumptions about an effect, variability, analysis, and sample size. It is not a measure of whether a result is true, and retrospective “observed power” does not provide a useful substitute for an estimate and its uncertainty. The registry record does not report a sample-size justification for this trial. It is therefore not possible to say what effect size the study was designed to detect or whether the completed study met a prespecified statistical target.

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("Ofatumumab/HDMP")
n      <- c(21)
events <- c(1)
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  Ofatumumab/HDMP  21  1  4.8  0.1  23.8  0.8  22.7  1.1  22.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record names complete response as the primary endpoint and lists secondary outcomes that include overall response, nodular partial response, partial response, stable disease, progressive disease, progression-free survival, treatment-free survival, and safety and tolerability measured via adverse events. It records ten outcome measures in total. The listed outcome names do not state how many statistical tests were performed or whether any adjustment for multiple testing was planned. The record lists no analyses, and a multiplicity strategy is not reported in the registry record.

General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. Prespecified priorities and appropriate methods can help readers distinguish a primary test from secondary or exploratory analyses. Without a reported analysis plan or results for the listed outcomes, it is not possible to assess how multiplicity was handled or to interpret any secondary finding as confirmatory.

Missing-data rules are also not reported in the registry record. In particular, the record does not state how participants without a complete-response assessment would be classified, whether all enrolled participants were intended for the primary analysis, or how missing survival follow-up would be addressed. It does not report the number assessed for the primary endpoint. General statistical context: the denominator and handling of missing outcomes can affect a binary response estimate, while missing follow-up can affect time-to-event analyses. These details are needed to understand the analysis population and the assumptions behind reported results.

No analysis population is identified in the registry record, and no primary endpoint result or analysis is listed. The count enrolled should not be assumed to equal the number analyzed. No interim-analysis plan, multiplicity adjustment, missing-data method, or prespecified statistical plan is reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

For the Ofatumumab/HDMP group, the registry record lists 21 participants at risk for serious adverse events and reports 0 participants affected. For other adverse events, 21 participants were at risk and 21 were affected. These figures describe participants affected in the posted safety categories; they do not give the number of individual events experienced by each participant.

The serious adverse-event list contains no reported terms. The record does not provide event descriptions, severity grades, timing, attribution, duration, or information on whether any event led to treatment changes. The field for deaths is not populated with a count, so deaths are not reported in the registry record. An unreported death count should not be read as zero.

General statistical context: safety counts depend on how events are defined, collected, and grouped. “Serious” and “other” are distinct categories in the posted record; the counts should not be combined. The record’s zero affected by serious adverse events is a descriptive count for this group, not proof that serious events are impossible or that the regimen is risk-free. The count of 21 affected by other adverse events does not indicate which events occurred or how burdensome they were. These data describe what the registry reports and do not establish a comparison with another treatment.

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

The record establishes that a completed phase II, single-group study enrolled 21 participants with relapsed or refractory CLL and examined ofatumumab with HDMP. It identifies iwCLL-WG defined complete response as the primary endpoint, with assessment two months after completion of therapy. It also describes a broad response definition involving blood, physical examination, symptom, marrow, and imaging criteria.

The record does not report the number of participants who achieved complete response. Therefore, it cannot support a numerical statement about the primary response result, its precision, or how many participants were assessed. The absence of that result is not evidence that the response count was zero, nor is it evidence that the endpoint was met. The primary outcome is simply not reported in the registry record.

The design also determines the scope of interpretation. Because there is no comparator group, the study cannot provide a randomized estimate of how outcomes differed from another treatment. Even if a response count were available, a single-group result would describe outcomes among participants in this study, not prove what caused those outcomes or predict an individual participant’s outcome.

The safety record reports zero participants affected by serious adverse events and 21 affected by other adverse events among 21 at risk in each category. It does not list serious-event terms or a death count. Those safety fields are descriptive and incomplete; they do not establish comparative safety or cover details that the registry record does not report.

General statistical context: a complete interpretation of a trial typically depends on estimates, uncertainty, analysis populations, missing-data handling, and the design’s ability to support causal comparisons. The record identifies the endpoint and some design and safety information, but does not report a primary endpoint analysis, statistical plan, or analysis population. The appropriate conclusion is limited to the trial structure and the specific descriptive counts recorded, not an efficacy or comparative claim.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and reported endpoint results need to be read together. The registry record defines complete response in detail and gives a time for assessment, two months after completion of therapy. That makes the intended outcome identifiable. Yet the primary response count is not reported in the registry record, so the central endpoint cannot be quantified or assessed for precision.

The design is also important to statistical interpretation. This phase II study is single-group, with allocation listed as NA and masking as none. It can describe outcomes in the group receiving ofatumumab and HDMP, but it has no concurrent control group for a direct treatment comparison. Recognizing this distinction prevents a within-group observation from being interpreted as a controlled treatment effect.

The safety fields show another useful distinction: the record separately reports participants affected by serious and other adverse events. It reports zero affected by serious adverse events and 21 affected by other adverse events, each among 21 at risk. The serious-event terms and death count are not reported. A reader can accurately describe those posted counts while also recognizing that they are not a complete account of event types, severity, or comparative risk.

General statistical context: registry records can document an intended question, trial structure, and selected outcomes without supplying the analyses needed to answer the question. Assessing a study statistically requires attention to the endpoint denominator, missing outcomes, analysis methods, uncertainty, and the role of any comparator. In this record, several of those elements are not reported. The result is a clear example of why study design and reporting completeness constrain what can be concluded, independently of the clinical topic.

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 principal limitation for interpreting the primary endpoint is that the registry record does not report the complete-response count or the number of participants assessed. Without these, neither a response proportion nor its precision can be described. The record also does not report a confidence interval, p value, or other analysis for the primary endpoint.

The single-group design has no comparator arm, so the study cannot directly estimate a contrast with another treatment. Masking is listed as none. The record does not describe blinded outcome assessment or methods to standardize assessment. These design features limit comparative interpretation, but the record alone does not establish whether they changed any particular result.

The record does not identify the analysis population, exclusions, or missing-data procedures. It is not possible to tell whether all 21 enrolled participants were assessed for complete response or included in each secondary outcome. No statistical analysis plan or sample-size justification is reported. The planning assumptions listed in the record are not a substitute for those details or for an observed endpoint result.

The safety information is limited to participant counts by broad category. Serious adverse-event terms are not listed, the death count is not reported, and detailed information about event timing, severity, or attribution is absent. Several named secondary outcomes are listed, but their results and analysis methods are not reported in the information available for this analysis. These gaps constrain interpretation of efficacy, safety, and completeness of follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL) — NCT01191190.
• Registry record last updated 2018-05-08; status last verified 2018-04.
• Results first posted 2015-11-20.
• 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 NCT01191190, a completed phase II, single-group study of ofatumumab with high-dose methylprednisolone in relapsed or refractory CLL. Enrollment was 21. The recorded start was 2010-08 and primary completion was 2012-02. The primary endpoint was iwCLL-WG defined complete response, assessed two months after completion of therapy.

The study had no comparator group, allocation was listed as NA, and masking as none. The primary complete-response count and analysis are not reported in the registry record. The record lists secondary response, survival, and safety outcomes, but their results are not included. For safety, it reports 0 participants affected by serious adverse events and 21 affected by other adverse events, with 21 at risk in each category. Serious-event terms and the death count are not reported in the registry record.