Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma (NCT01716208), a na phase 2 study. The primary outcome is Response to Therapy.

2. Clinical Question

The study rationale, as described in the registry, concerns complement levels and the possibility of combining FFP with ofatumumab. The stated aims also include examining blood complement levels and whether raising them with FFP may help control leukemia. These are research questions, not findings: the registry record does not report a result for the primary response outcome or a result establishing a relationship between complement levels and leukemia control.

The central statistical question is therefore descriptive: what outcomes were recorded among participants treated in this single group? Without a comparator, any observed outcome could not by itself distinguish an intervention effect from other explanations, including the underlying course of disease or other influences on outcomes. The available record gives enrollment and selected safety counts, but does not give an efficacy count or an estimated treatment effect.

3. Trial Design

This was a Phase II, completed, single-group study, listed under NCT01716208. The registry records an enrollment of 12 and identifies chronic lymphocytic leukemia as the condition. Its official title describes a study of ofatumumab and FFP in people with relapsed or refractory chronic lymphocytic leukemia. The listed intervention is “Ofatumumab + Fresh Frozen Plasma.”

The trial is recorded as having no masking and no allocation to a randomized comparison. A single group means the participants received the listed intervention without a separate control group in the trial record. The study therefore provides no within-trial comparison of outcomes under the intervention versus outcomes under a different treatment or no intervention. This limits what can be concluded about whether differences in outcomes are attributable to the regimen.

The arm description outlines an intravenous ofatumumab schedule, beginning with an initial dose and continuing with weekly and then less frequent doses. It also says that two units of FFP were to be administered before ofatumumab, with an exception that is cut off in the recorded description. The full details of that exception and the complete FFP administration instructions are not reported in the registry record; they should not be inferred from the abbreviated text.

The registry lists the study start as 2013-01-14, primary completion as 2019-10-01, and status as completed. It lists Joseph Tuscano as sponsor. These administrative details describe the registered trial, but do not supply information about the conduct of individual visits, adherence, or the timing of outcome assessments beyond the primary outcome timeframe, which is “Up to 37 months.” Those details are not reported in the registry record.

The design is suited to describing outcomes observed in the treated group, subject to the completeness of outcome reporting. It is not a randomized comparison, and its safety and response counts should not be read as comparative estimates. The registry record does not report a sample-size justification or enough outcome information to evaluate an efficacy estimate.

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

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 Response to Therapy, measured over Up to 37 months..

The primary endpoint is titled “Response to Therapy” and is recorded as a count of participants. The registry description defines it using complete or partial response and progression-free survival, with assessment by National Cancer Institute Working Group and International Workshop on Chronic Lymphocytic Leukemia criteria. The stated timeframe is “Up to 37 months.” The precise operational relationship between the response categories and progression-free survival is not further described in the registry record.

Response endpoints are used in clinical research to summarize whether participants meet prespecified criteria for a change in disease status. Using named assessment criteria can make outcome classification more consistent than an informal judgment, provided the criteria are applied as intended. A participant count is a descriptive measure of how many people meet the endpoint definition; by itself, it does not express the uncertainty around that count or establish a treatment effect.

The registry record does not report a value for this primary endpoint. It therefore does not show how many participants met the response definition, nor does it provide an estimate with a confidence interval or a comparison against another group. The endpoint definition and timeframe identify what was intended to be assessed, but they are not a report of the observed result.

Progression-free survival is a time-to-event concept in general: it concerns the time until disease progression or another event specified by the study definition. The registry wording includes this term but does not report event times, a survival estimate, or further details of the endpoint construction. Those elements cannot be reconstructed from the stated endpoint title and definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts by identifying what the design can estimate. This trial is recorded as a single group, with 12 enrolled participants and no allocation to a randomized comparison. Its observed counts, where reported, describe that group. They do not estimate a difference between the regimen and a control condition. General statistical principle: a treatment effect is usually expressed as a contrast between outcomes under different conditions; without a comparator, that contrast is not available from the trial alone.

What does a participant count tell us?

The primary outcome is specified as a count of participants meeting the response definition. A count is directly interpretable as a number of people classified under that endpoint, assuming the outcome was assessed and recorded. But the registry record does not provide that count. It therefore cannot support calculation or interpretation of an observed response proportion, and no such proportion should be inferred from enrollment or from safety counts. A count also does not, on its own, describe precision. General statistical principle: an interval estimate can communicate uncertainty around an estimate, while a point estimate alone gives only one value.

How should confidence intervals be understood?

General statistical explanation: a confidence interval is a range generated by a statistical method to express uncertainty about an estimated quantity. Its width depends on factors such as the amount of information in the data and the variability of the outcome. It is not a guarantee that the true value lies in that particular interval. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated. For safety counts, the record gives counts and selected percentages but does not provide confidence intervals.

Why does the single-group design matter?

Without a randomized control group, participants’ outcomes cannot be compared with outcomes that would have occurred under a different assigned condition within the same trial. General statistical principle: randomization can make treatment groups comparable on average with respect to measured and unmeasured characteristics, while a single group offers no such concurrent comparison. The trial can describe outcomes recorded among participants, but it cannot isolate the effect of the combination from other explanations. This is a design limitation, not a claim that the observations themselves are invalid.

What do the safety summaries represent?

The registry lists 12 participants at risk in the intervention group for both serious and other adverse events. It records 2 participants affected by serious adverse events, 10 affected by other adverse events, and 1 death. It also lists lung infection and atrial fibrillation as top serious adverse-event terms, each at 8.3%. These are descriptive entries. General statistical principle: adverse-event summaries depend on definitions, observation periods, and reporting practices. The registry information does not describe those details sufficiently to assess whether events overlapped, how long participants were observed for safety, or whether investigators considered an event related to the intervention.

What do the planning assumptions mean?

The described sample-size illustration is explicitly a planning calculation based on an observed effect, rather than the trial’s own design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For time-to-event tables, the illustration describes a total event count; for other outcomes, it describes participants per arm. These are assumptions for a hypothetical planning exercise, not features of the single-group trial as conducted. A planning estimate is not observed power, and it does not show that the study had a particular probability of detecting an effect.

The registry record does not give the trial’s sample-size justification, an analysis plan, or primary outcome results. It also records 0 analyses. Therefore, there is no documented inferential procedure, adjustment strategy, or treatment-effect estimate to explain. General statistical principle: an analysis plan specifies how outcomes, populations, missing observations, and statistical tests will be handled. Without those details, readers cannot determine whether the reported analyses followed prespecified methods or how the uncertainty around an outcome was assessed.

The registry identifies the response assessment criteria and the timeframe “Up to 37 months,” but does not report the outcome count or further details about how progression-free survival was defined or analyzed. General statistical principle: time-to-event analyses can account for differing follow-up durations and participants whose event has not been observed by the end of follow-up, but they require information about event timing and censoring. Such analysis details and results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures, including the primary response outcome and secondary outcomes concerning toxicities, overall survival, and reduction in complement levels (CH50). It records 0 analyses. No multiplicity strategy is reported in the registry record. General statistical principle: when several outcomes are tested, the chance of at least one apparently positive finding can increase if each is assessed independently without an adjustment or a prespecified hierarchy. The record does not indicate whether any adjustment, hierarchy, or other multiplicity approach was planned.

Missing-data handling is not reported in the registry record. The record does not state how participants with incomplete outcome assessments, withdrawal, or unavailable follow-up would be handled. This matters in general because missing observations can affect both the estimate and its uncertainty, especially if the reason for missingness is related to outcome status. No assumptions about the extent or pattern of missing data can be made from the information recorded.

Analysis populations are also not reported in the registry record. It does not identify whether any outcome analysis was intended to include all enrolled participants, only participants who received treatment, or another defined group. These approaches answer different questions in general, so knowing the analysis population is necessary to interpret a reported result. Since no primary outcome result or analysis is listed, there is no analysis population to evaluate.

The registry does not report interim analyses or a statistical analysis plan. These absences prevent assessment of planned stopping rules, prespecified hypotheses, or whether the final analysis followed a defined procedure. They should be treated as reporting limitations rather than evidence that a particular method was or was not used.

11. 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: lung infection (8.3%), atrial fibrillation (8.3%).

The registry records safety information for the single intervention group, with 12 participants listed at risk. It reports 2 participants affected by serious adverse events and 10 affected by other adverse events. One death is recorded. The top serious adverse-event terms are lung infection and atrial fibrillation, each reported as 8.3%. These values describe entries in the registry; they do not establish that the intervention caused an event or death.

Serious adverse events and other adverse events are separate summary categories in the record. The participant counts should not be added together or treated as mutually exclusive: the record does not say whether participants could appear in both categories. It also does not report event counts per participant, timing, duration, investigator attribution, or the detailed criteria used for event classification. The death entry is not accompanied by information about cause or relationship to treatment.

The listed percentages are registry-reported values and should be read as reported, without inferring additional event counts from them. General statistical principle: safety percentages from a small group can be unstable, and a percentage alone does not show the range of uncertainty. No confidence intervals are reported for these safety summaries. These data can describe recorded events, but cannot provide a controlled comparison of safety between treatments.

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

The record documents a completed Phase II study of ofatumumab with FFP in a single group of 12 participants with chronic lymphocytic leukemia. It describes the primary response endpoint, its assessment criteria, and a timeframe of up to 37 months. It also records selected safety counts. These details are useful for understanding the registered study and the kinds of outcomes it intended to examine.

The record does not report the primary response result. It therefore does not establish how many participants met the response definition, how precise an estimate would be, or whether the outcome differed from what might occur without the intervention. The absence of a comparator is especially important: even a reported response count in this single group would not by itself establish that the regimen caused the observed outcomes.

The adverse-event entries describe events recorded among the participants, but they do not establish causation. The group-level safety counts and listed serious-event terms cannot be used to compare this regimen with another approach because no comparison group is reported. The record also lacks details needed to assess event timing, attribution, and follow-up.

General statistical principle: clinical trial results are strongest when the outcome definition, analysis population, missing-data approach, estimate, and uncertainty are all available. Here, several of those elements are not reported in the registry record, and no analyses are listed. The study’s completed status should not be interpreted as a substitute for its missing outcome results.

The statistical meaning is consequently limited but clear: the record describes a small, uncontrolled study and reports selected safety observations, while leaving the primary efficacy outcome unquantified. It cannot support a conclusion about whether the intervention improves outcomes, nor can it establish that it does not. Those conclusions would require results and a design capable of addressing the relevant comparison.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a registered research question and a reported result. The registry gives a primary endpoint definition and names assessment criteria, but does not report the endpoint value. Knowing what was intended to be measured is not the same as knowing what was observed. Readers need both the outcome definition and the results to evaluate an estimate.

It also illustrates how design shapes inference. A single-group study can document events and describe outcomes among its participants, but it does not supply a concurrent control group. This limits the ability to separate an intervention-associated outcome from other explanations. The distinction remains important regardless of whether the study is complete or how clearly its intervention is described.

The safety entries demonstrate why counts need context. The record reports serious and other adverse-event counts, a death, and two serious-event terms with percentages. Without details on attribution, timing, event overlap, follow-up, and uncertainty, these entries are descriptive rather than comparative. General statistical principle: a transparent account of how outcomes were collected and analyzed helps readers judge the scope and reliability of such summaries.

Finally, the record lists several outcome measures but no analyses. This highlights the role of transparent analysis reporting, including a defined analysis population, missing-data handling, and a plan for interpreting multiple outcomes. Those methods are not reported. The statistical lesson is not a judgment about the intervention; it is that the available record supports only a limited description of the study, not a complete evaluation of its efficacy or comparative safety.

14. 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 outcome result is not reported in the registry record. Although the endpoint is described as a participant count based on response and progression-free survival criteria, there is no reported count, estimate, or uncertainty measure. The efficacy question therefore remains unquantified in this record.

The study has a single group and no randomized comparator. This means there is no within-trial basis for estimating a relative treatment effect. The enrollment of 12 also means the reported safety observations come from a limited group; no uncertainty intervals are provided. These features constrain the precision and scope of any description, even when counts are available.

The endpoint description leaves some details unclear. It refers to complete or partial response and progression-free survival, but does not further explain their relationship in the endpoint definition or report event-time analysis details. The timeframe is “Up to 37 months,” but the record does not provide individual follow-up duration, censoring information, or results over time.

The intervention description is incomplete in the registry record: it outlines ofatumumab dosing and FFP administration but ends before the full exception and administration details are given. No inference should be made about the missing text. Further limitations include the absence of a reported statistical analysis plan, analysis populations, missing-data methods, multiplicity strategy, and interim analyses. These matters are not reported in the registry record.

The safety summaries also lack context on event timing, attribution, duration, and overlap between categories. The record reports one death but does not give its cause or relationship to the intervention. Collectively, these limitations mean the available information is insufficient for a full assessment of efficacy, precision, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma — NCT01716208.
• Registry record last updated 2021-05-11; status last verified 2021-04.
• Results first posted 2021-05-11.
• 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.

18. Record Summary

NCT01716208 is a completed Phase II, single-group trial of ofatumumab with fresh frozen plasma in chronic lymphocytic leukemia. The registry lists 12 participants, no masking, and no randomized allocation. Its primary outcome is “Response to Therapy,” described using complete or partial response and progression-free survival criteria, with assessment by National Cancer Institute Working Group and International Workshop on Chronic Lymphocytic Leukemia criteria and a timeframe of up to 37 months.

The primary outcome result and inferential analyses are not reported in the registry record. The safety entries list 2 participants with serious adverse events, 10 with other adverse events, and 1 death. Lung infection and atrial fibrillation are listed as top serious adverse-event terms, each at 8.3%. The single-group design supports descriptive interpretation only; it does not provide a randomized comparison or establish causation.