Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia (NCT00625729), a na phase 1, phase 2 study. The primary outcome is Number of Patients Exhibiting Natural Killer Cell Expansion.

2. Clinical Question

The study asks whether donor natural killer (NK) cells can be expanded after infusion in patients receiving a treatment combination that includes rituximab, aldesleukin, and chemotherapy. It is registered as a phase I/II trial and includes patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia. Its primary endpoint focuses on a biological measure: whether circulating donor-derived NK cells meet the registry's definition of successful expansion at Day 14.

The registry's rationale describes aldesleukin as a way to stimulate NK cells and says laboratory treatment of donor NK cells with aldesleukin may help them kill cancer cells after infusion. It also describes rituximab and chemotherapy before infusion as part of the treatment approach. These are the stated rationale and purpose, not evidence that the approach achieved a clinical benefit.

Because this is a single-group study, its primary question is not a randomized comparison of the combination against another treatment. The record does not report a primary endpoint result, so it does not establish how many participants met the cell-expansion definition. It also does not report results for the listed secondary outcomes, which include overall response, disease progression, adequate NK cell infusion, interleukin-15 production and NK cell expansion, and overall survival.

3. Trial Design

The registry classifies the study as phase I and phase II, with a single-group model, no masking, and allocation listed as not applicable. The single treatment group is described as patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with donor NK cell infusion, rituximab, aldesleukin, and chemotherapy. The enrollment was 6. The sponsor is Masonic Cancer Center, University of Minnesota.

The intervention list includes aldesleukin, allogeneic NK cells, rituximab, cyclophosphamide, and fludarabine phosphate. The study title and brief summary describe the sequence as chemotherapy and rituximab followed by donor NK cell infusion, with aldesleukin treatment of the cells in the laboratory and aldesleukin after infusion. The registry record does not provide further details about dose, schedule, eligibility criteria, or treatment delivery.

The recorded start is 2008-01, and primary completion is 2009-12. The study status is terminated. A reason for termination is not reported in the registry record. The record does not state whether the planned enrollment was reached or whether the study ended early relative to its intended schedule.

The absence of randomization and a comparator is central to interpretation. Outcomes in this group can describe what was recorded among participants receiving the treatment combination, but they cannot isolate the effect of any one component or establish a difference from another treatment. The record does not report a sample-size justification or provide enough information to infer the intended statistical design beyond its phase and single-group classification.

The listed outcomes include the primary measure of NK cell expansion and secondary measures concerning interleukin-15 production and NK cell expansion, overall response, disease progression, adequate NK cell infusion, and overall survival. Outcome results and analysis details for these measures are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

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 Exhibiting Natural Killer Cell Expansion, measured over Day 14.

The primary endpoint is the number of participants exhibiting NK cell expansion, assessed at Day 14. The registry defines successful expansion as an absolute circulating donor-derived NK cell count of >100 cells/μl 14 days after infusion, together with <5% donor T and B cells in the mononuclear population. This endpoint therefore combines a threshold for the donor NK cell count with a restriction on the proportion of donor T and B cells.

As a biological endpoint, the measure is intended to capture whether donor-derived NK cells are present in circulation at a specified level after infusion. The accompanying cell-composition criterion distinguishes the desired NK cell expansion from a population that exceeds the stated donor T and B cell limit. The endpoint is binary at the participant level: a participant either meets the registry's definition or does not. The record does not report the number who met the definition.

General: A biological endpoint can help describe an early treatment process without directly measuring how a participant feels, functions, or survives. It may be useful for characterizing cell expansion, but it should not be treated as interchangeable with clinical outcomes such as overall response or survival. Those outcomes appear separately among the registry's secondary measures.

The Day 14 timing and the threshold are part of the stated endpoint definition. The record does not report details about how samples were collected, how cell counts were measured, how missing or unevaluable measurements were handled, or whether the endpoint definition changed during the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study records outcomes among participants who receive the listed treatment combination. Its direct descriptive target is the experience of that treated group, subject to who enrolled, who was assessed, and how outcomes were recorded. Without a comparison group, the design does not estimate a randomized treatment contrast. A before-and-after interpretation would require corresponding measurements and a defined analysis, neither of which is reported in the registry record for the primary endpoint.

The combination includes multiple biological and drug interventions. In a single group receiving these interventions together, observed outcomes cannot identify the separate contribution of each component. Other influences on an outcome also cannot be distinguished from treatment effects using a treatment-group count alone. This is why a descriptive result, if reported, would need to be kept separate from a causal claim.

What does the primary endpoint count?

The primary endpoint is a participant count based on a binary definition. The registry specifies that successful NK cell expansion requires an absolute circulating donor-derived NK cell count of >100 cells/μl at Day 14 and <5% donor T and B cells in the mononuclear population. Both conditions form part of the definition. The endpoint is not a mean cell count, a change from baseline, or a time-to-event measure as described in the registry.

To interpret such a count, readers would ordinarily need the number meeting the definition and the number assessed. Neither is reported in the registry record. The enrollment of 6 does not by itself reveal the endpoint denominator: some participants could have missing or unevaluable measurements, and the registry does not say whether that occurred. No imputation method or missing-measurement rule is reported.

What is a confidence interval?

General: A confidence interval is a range of values generated by a statistical procedure to communicate uncertainty around an estimate. Its width depends on the amount and variability of information and on the method used. A confidence interval does not fix limitations in the study design, such as the absence of a comparison group, and it cannot be interpreted when the estimate and interval are not reported. No confidence interval for the primary endpoint is reported in the registry record.

For a binary endpoint, an analysis might report a count and a proportion, sometimes with an interval describing uncertainty in the proportion. The registry identifies the endpoint as a participant count but does not report a proportion, interval, or inferential test. No statistical method for the primary endpoint is reported in the registry record, so a particular model or interval method should not be attributed to the study.

How should the study's phase and enrollment be understood?

The record labels the study phase I and phase II, but does not provide a phase-specific analysis plan or explain how the phases were organized. Enrollment was 6. The record does not report a sample-size justification, target enrollment, or assumptions used to set the enrollment. The enrollment figure should not be treated as evidence that a planned precision or power target was met.

Planning illustrations are not observed power. The registry record does not report a study-specific sample-size calculation or a rationale for the enrollment. Any hypothetical sample-size calculation based on an observed effect would depend on assumptions about the effect to detect, significance level, allocation, and statistical method; it would not describe the trial's original planning unless the record documented those choices. The record does not report an observed primary effect from which to infer such planning.

What is over-dispersion?

General: Over-dispersion occurs when the variability in data is greater than a statistical model assumes. If ignored, uncertainty estimates from that model can be too small, making results appear more precise than warranted. This concept can matter for count outcomes, but it does not establish that over-dispersion was present in this study. The registry does not report a count model, dispersion estimate, or related diagnostic.

What is multiplicity?

General: Multiplicity arises when several outcomes or statistical tests are considered, increasing the chance of at least one apparently unusual result if each is interpreted without regard to the others. A prespecified testing strategy can clarify which outcomes are primary and how secondary findings should be interpreted. The registry lists several secondary outcomes alongside the primary endpoint, but does not report a multiplicity procedure or a statistical analysis plan. The order in which outcomes are listed does not establish a testing hierarchy beyond the primary designation.

The record lists no analyses. That absence means there is no registry-reported analysis method, estimate, test statistic, or inferential result to assess. It does not establish what analyses may or may not have been performed outside the registry record. In particular, the record does not report adjustment for covariates, subgroup analyses, interim analyses, or a plan for handling incomplete outcome data.

As a result, interpretation should remain anchored to the information actually recorded: a single-group phase I/II study, enrollment of 6, a defined Day 14 biological endpoint, a list of secondary outcomes, and no reported outcome analyses. Statistical explanations can clarify what would ordinarily be needed, but they cannot fill in absent results or methods.

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("Patients Treated With Natural Killer Cells")
n      <- c(6)
events <- c(0)
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  Patients Treated With Natural Killer Cells  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and secondary outcomes concerning interleukin-15 production and NK cell expansion, overall response, disease progression, adequate NK cells infused, and overall survival. It does not report a multiplicity adjustment, a hierarchy for testing secondary outcomes, or a statistical analysis plan. Without those details, the intended inferential status of any secondary finding is not reported in the registry record.

No analyses are listed. The registry record also does not report how missing data were handled, how many participants were evaluable for each outcome, or whether participants were analyzed according to a defined analysis population. The total enrollment of 6 does not establish the denominator for each endpoint. The record does not state whether any participants withdrew, missed assessments, or had unevaluable measurements.

General: Missing outcome information can affect both the denominator and the interpretation of a result. An analysis that excludes participants with missing measurements may describe a selected subset rather than everyone enrolled. An imputation method can make different assumptions about unobserved values. Neither approach can be attributed to this study because the registry record does not describe one.

The status is terminated, but a reason is not reported in the registry record. There is no basis in the record for deciding whether termination affected planned analyses or outcome collection. The relationship between the registry's listed outcomes and any analysis that may have been completed is also not reported.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: death - disease progression nos (50.0%), infection (33.3%), cardiac arrhythmia (16.7%), neutrophils/granulocytes (anc/agc) (16.7%), pulmonary - obstruction/stenosis of airway (16.7%).

The registry lists 6 participants at risk for serious adverse events and 5 affected. For other adverse events, it lists 6 at risk and 0 affected. The death count is not reported in the registry record. These entries are safety summaries; the record does not provide a comparison group or a detailed account of event timing, duration, severity grading, or attribution to treatment.

Listed serious-event terms include Death - Disease Progression NOS at 50.0%, Infection at 33.3%, and Cardiac Arrhythmia, Neutrophils/granulocytes (ANC/AGC), and Pulmonary - obstruction/stenosis of airway, each at 16.7%. The record does not clarify whether participants could contribute to more than one term or provide event counts alongside these percentages. The listed term Death - Disease Progression NOS should not be read as a reported trial death count, because the death count itself is not reported in the registry record.

General: Adverse-event listings describe events recorded under the registry's reporting conventions. They do not, by themselves, establish that treatment caused an event. With no comparator group, these figures cannot show whether the listed events were more or less frequent than under another treatment.

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

The registry record documents a phase I/II, single-group study of donor NK cell infusion combined with rituximab, aldesleukin, cyclophosphamide, and fludarabine phosphate. It specifies a primary biological endpoint at Day 14 and provides a threshold-based definition of successful NK cell expansion. It also lists clinical and biological secondary outcomes and adverse-event entries.

What the record does not establish is the primary endpoint result. It does not report how many participants met the expansion definition, the number with evaluable measurements, or an estimate of uncertainty. Results for the secondary outcomes are also not reported in the registry record. Therefore, the record cannot support a conclusion about the observed extent of NK cell expansion, response, progression, or survival.

The design also limits what an outcome could mean. Since there is no comparator arm, a result among participants receiving the treatment combination would not be a randomized estimate of benefit relative to another approach. The design cannot separate the effects of individual treatment components. It also cannot, without additional information and assumptions, distinguish treatment effects from other influences on the observed outcomes.

The serious adverse-event entries describe events reported among the treated participants. They should not be interpreted as proof that the treatment caused the events or as a comparative safety estimate. The death count is not reported in the registry record, even though a death-related term appears in the serious-event listing.

The appropriate conclusion is narrow: the registry describes a terminated, small, single-group phase I/II study with a specified cell-expansion endpoint and listed safety events, but it does not report outcome analyses. The status, design, and adverse-event entries cannot substitute for missing endpoint results, a comparator, or an analysis plan. Any broader conclusion about efficacy, comparative safety, or the reason for termination would go beyond what the registry record reports.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly specified biological endpoint and the absence of a reported endpoint result. The registry states what successful NK cell expansion means and when it is assessed: at Day 14, using a donor-derived cell-count threshold and a limit on donor T and B cells. That level of definition helps identify what the study intended to measure, but a definition alone does not show whether participants met it.

The single-group design is another important feature. It allows the registry to describe a treatment group, but does not create a randomized comparison. This distinction matters when interpreting any outcome: a group-level observation is not the same as evidence that treatment changed an outcome relative to an alternative. Because the regimen includes several interventions, a single-group result would not identify the contribution of each component.

Enrollment was 6, and the study is labeled phase I and phase II. The registry does not report the planned sample-size rationale, the intended precision, or the analysis strategy. These omissions limit the ability to evaluate whether the study was designed to answer a particular statistical question or how confidently any estimate could be interpreted.

The record also lists several secondary outcomes and safety information, while reporting no analyses. This illustrates why outcome registration, outcome reporting, and statistical interpretation are distinct: a listed measure signals what was recorded as an outcome, but does not establish that a result is available or that a comparison was made.

Finally, the terminated status is recorded without an explanation. Statistical interpretation cannot determine the reason for termination from status alone. Together, these features make the record most useful as a description of design, endpoint definition, and the limits of the available results, rather than as a basis for a treatment-effect estimate.

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.

Several limitations specific to this study constrain interpretation. The enrollment was 6, and the study has a single-group design with no comparator. The record therefore does not support a randomized comparison, and any observed outcome could not be attributed to an individual component of the treatment combination from this design alone.

The primary endpoint result is not reported in the registry record. The record also does not report the number of participants assessed at Day 14, the endpoint denominator, or how missing measurements were handled. Without these details, neither the observed frequency of successful expansion nor its precision can be evaluated.

The registry lists secondary outcomes but does not report their results or analyses. It does not provide a statistical analysis plan, a multiplicity strategy, a sample-size justification, or an explanation of whether interim analyses occurred. These details are not reported in the registry record, so the intended analysis and handling of multiple outcomes cannot be assessed.

The study is marked terminated, but the reason is not reported in the registry record. The record does not state whether termination affected enrollment, outcome collection, or analysis. Safety reporting includes summary figures and event terms, but does not provide event timing, treatment attribution, or a comparator. The death count is not reported in the registry record.

The phase I/II label and the defined biological endpoint help characterize the study, but do not resolve these evidence gaps. The available registry information is insufficient to assess endpoint results, clinical outcomes, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia — NCT00625729.
• Registry record last updated 2017-12-28; status last verified 2017-12.
• Results first posted 2010-07-30.
• 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

NCT00625729 is a phase I/II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. It enrolled 6 participants with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia and is listed as terminated. The recorded start is 2008-01, and primary completion is 2009-12.

The intervention combined donor allogeneic NK cell infusion with rituximab, aldesleukin, cyclophosphamide, and fludarabine phosphate. The primary endpoint was the number of participants exhibiting NK cell expansion at Day 14, defined using a donor-derived NK cell count of >100 cells/μl and <5% donor T and B cells in the mononuclear population.

Secondary outcomes include measures of interleukin-15 production and NK cell expansion, overall response, progression, adequate NK cell infusion, and overall survival. The registry record does not report primary or secondary outcome results, analyses, a sample-size justification, or the reason for termination. Safety entries list serious and other adverse events, while the death count is not reported in the registry record.