Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (NCT00398112), a na phase 2 study. The primary outcome is Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart.

2. Clinical Question

This question concerns whether a response meeting the registry's stated criteria was recorded during treatment. It does not by itself compare sunitinib with another treatment or with no treatment. The study enrolled 18 participants, but the response count and the number assessed for the primary endpoint are not reported in the registry record.

The endpoint combines complete response (CR) and partial response (PR). Under the stated NCI working group criteria, a CR requires no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms, a normal complete blood count, and confirmation by bone marrow aspirate and biopsy. A PR requires a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver or spleen size, and the presence or absence of constitutional symptoms, plus at least one specified blood-count improvement. A response also must be confirmed on consecutive evaluations separated by at least 4 weeks.

The primary question is therefore about a defined response count over a treatment period of up to 12 cycles. The registry record does not report whether any participants met the endpoint, how response assessments were handled when unavailable, or what statistical method was used to summarize the result.

3. Trial Design

This was a phase II, single-group study of sunitinib malate for relapsed or refractory CLL or SLL. The registry lists an enrollment of 18 and identifies the National Cancer Institute (NCI) as sponsor. The study is marked completed. Its recorded start is 2007-08, and its primary completion is 2008-11.

Participants in Arm I received oral sunitinib malate daily on days 1-28. The treatment schedule repeated every 28 days for up to 12 courses, subject to disease progression or unacceptable toxicity. The registry also lists a pharmacological study and laboratory biomarker analysis as interventions; it does not describe their procedures or how they related to the primary endpoint.

Allocation is listed as not applicable, masking as none, and the model as single-group. Consequently, the design does not include a concurrently assigned control group for estimating a between-group treatment contrast. A response observed during treatment can be described, but the single-group design alone cannot establish what would have happened to the same participants under a different treatment or without this treatment.

The registry defines a primary outcome as the number of participants with a confirmed CR or PR on two consecutive evaluations at least 4 weeks apart, with a timeframe of duration of treatment, up to 12 cycles. It also lists complete response rate in patients with B-cell CLL, survival time, progression-free survival and duration of response as secondary outcomes. Outcome results for these measures are not reported in the registry record.

The record does not report a detailed statistical analysis plan, an intended analysis population, a sample-size justification, or an interim-analysis plan. The trial's recorded enrollment should not be interpreted as the number included in every outcome analysis: endpoint-specific assessment counts are not reported.

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.

Before assignment: All participants were eligible and included in all analyses.

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 Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart, measured over Duration of Treatment (up to 12 cycles).

The primary endpoint is a count: the number of participants with a confirmed response, where response means CR or PR on two consecutive evaluations at least 4 weeks apart. Its timeframe is duration of treatment, up to 12 cycles. Requiring consecutive evaluations makes the endpoint depend on confirmation rather than a single response assessment.

The registry uses National Cancer Institute working group criteria. A CR requires no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms, a normal complete blood count, and confirmation by bone marrow aspirate and biopsy. A PR requires a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver or spleen size, and the presence or absence of constitutional symptoms, plus at least one of the following: at least 1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin, or 50% improvement for these parameters without transfusions.

General statistical context: a response count is a direct summary of how many participants meet the stated definition; it is not a measure of the size or duration of benefit for each participant. A response rate would require a defined denominator as well as the response count. The registry record gives the endpoint definition and enrollment, but does not report the endpoint result or its analysis denominator. It therefore does not permit a response rate or its precision to be read from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome in terms of participants with an event: a participant either meets the confirmed-response definition or does not. The reported endpoint is framed as a number of participants, not as a continuous measurement. No endpoint result or statistical analysis is listed in the registry record, so the method used to analyze this outcome is not reported there.

What does confirmation contribute?

The response definition requires CR or PR on two consecutive evaluations at least 4 weeks apart. General statistical context: confirmation rules can reduce reliance on a single assessment that might be temporary or uncertain. They also make the endpoint depend on repeated measurement and on the availability and timing of follow-up assessments. How the trial handled missing or delayed assessments is not reported in the registry record.

What does a count tell us?

A count reports the number meeting a definition. To interpret that count as a rate, a reader also needs to know the denominator—the number of participants assessed or included in the analysis. General statistical context: a rate and its confidence interval communicate different things. The rate describes the observed proportion under a stated denominator; the interval expresses uncertainty around that estimate under the chosen statistical method. Neither the response count, endpoint denominator nor confidence interval is reported in the registry record.

A count alone would not show the distribution of response timing, duration or participant characteristics. The registry separately lists duration of response, survival time and progression-free survival as secondary outcomes, but does not report their results. Definitions for those outcomes beyond their names, as well as the statistical methods used for them, are not reported in the registry record.

Why does the single-group design matter?

The trial is recorded as single-group, with no masking and allocation listed as not applicable. General statistical context: random allocation to a concurrent comparison group can help make groups comparable, on average, with respect to both known and unknown factors. Without a randomized comparator, a within-study response count is descriptive rather than a randomized estimate of a treatment contrast. The record does not describe another control condition or an adjustment strategy intended to address this limitation.

Open-label treatment means masking is not recorded for the study. General statistical context: knowledge of treatment assignment can affect some aspects of care, follow-up, reporting or assessment. The record identifies the response criteria but does not report whether endpoint assessors were independently masked or what procedures were used to ensure consistent assessments.

What can planning calculations show?

General statistical context: sample-size calculations estimate the amount of information a future design might need to detect a specified effect under stated assumptions. They are planning illustrations, not observed power. The planning assumptions recorded for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect described as a stated fraction of the observed effect. Those assumptions do not describe the actual single-group design, and no trial-specific sample-size justification is reported in the registry record. The calculation results and the fractions used are not reported in the registry record.

General statistical context: over-dispersion matters when observed variability exceeds what a simple model assumes; ignoring it can make uncertainty estimates too small. The primary outcome is a participant count, and no dispersion parameter or model-based analysis is reported. A model choice, including any allowance for over-dispersion, should not be attributed to this study without a reported analysis plan or results.

What analysis details are missing?

The registry record lists no analysis records. It does not report a statistical model, significance test, confidence interval method, covariate adjustment, subgroup analysis plan, interim analysis, multiplicity adjustment, or handling of missing data. This absence does not establish that none of these procedures occurred; it means they are not described in the registry record. Statistical interpretation should therefore remain limited to the design, outcome definition and safety counts that are actually recorded.

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("Sunitinib Malate")
n      <- c(18)
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  Sunitinib Malate  18  0  0.0  0.0  18.5  -0.0  17.6  0.1  17.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes: complete response rate in patients with B-cell CLL, survival time, progression-free survival and duration of response. It does not report results for these outcomes. The registry record lists no analysis records, and a planned testing hierarchy or multiplicity adjustment is not reported in the registry record.

General statistical context: when several outcomes or hypotheses are tested, the chance of at least one apparently unusual result can increase if each is assessed independently at the same threshold. Methods such as prespecifying a primary outcome, hierarchical testing or adjustment can address different multiplicity concerns. The record does not establish which approach, if any, was used, so no claim about error-rate control can be made.

Missing-data procedures and analysis populations are also not reported in the registry record. It does not say how participants without two consecutive response evaluations were classified, whether incomplete evaluations were excluded, or how missing follow-up affected the secondary outcomes. The endpoint denominator and numbers assessed are not reported. Enrollment of 18 should not be treated as an endpoint analysis count.

General statistical context: analysis populations matter because estimates can differ depending on which participants are included and how protocol deviations or missing outcomes are handled. The registry record does not identify an intention-to-treat, per-protocol or other analysis population. As a result, the basis for any outcome analysis cannot be checked from the recorded information.

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 Sunitinib Malate group, the registry records 18 participants at risk for serious adverse events and 0 affected. It records 18 participants at risk for other adverse events and 18 affected. These are participant counts in separate reporting categories; the record does not give event-level totals or state whether a participant experienced more than one event.

The serious-event count describes the registry's recorded count of participants affected in that category. It does not establish that no adverse events of any kind occurred: the other adverse-event category records affected participants. The registry record does not report serious adverse event terms, and it does not provide details such as event type, severity beyond the category distinction, timing, duration, attribution or outcome.

General statistical context: a zero count in a study group does not demonstrate that the underlying risk is zero. The precision of a safety estimate depends on the number observed, the number assessed and the follow-up and reporting procedures. The registry gives the at-risk counts for these categories but does not report additional safety-analysis methods or a confidence interval. The figures should therefore be read as recorded counts, not as a complete or comparative estimate of risk.

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

The registry record describes the conduct and planned outcome of a single-group phase II study of sunitinib malate in relapsed or refractory CLL or SLL. Its primary endpoint is a confirmed CR or PR on two consecutive evaluations at least 4 weeks apart during treatment, up to 12 cycles. The primary endpoint result is not reported in the registry record.

That missing result prevents a reader from determining how many participants met the response definition, what proportion they represented, or how precise an estimate would be. The listed enrollment of 18 does not supply an outcome count or confirm how many participants were assessed. No response estimate can be inferred from the endpoint definition, treatment schedule or safety counts.

The record also does not report findings for the listed secondary outcomes: complete response rate in patients with B-cell CLL, survival time, progression-free survival and duration of response. It therefore cannot establish the frequency or duration of responses, or describe survival outcomes, from the recorded information.

Even if a response count were available, general statistical context is important: results in a single-group study describe outcomes in the enrolled group but do not, by themselves, isolate the effect of treatment from other influences or establish what would have occurred under a comparator. The registry records no randomized comparison group.

The adverse-event counts indicate 0 participants affected in the serious category and 18 affected in the other category, among 18 at risk in each. Those figures do not provide event descriptions or a comparative safety estimate. Overall, the registry record supports a description of the study design, endpoint definition and recorded safety counts, but does not report the efficacy outcome needed to assess the primary question.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly specified endpoint and a reported result. The registry defines a confirmed response using named criteria and consecutive evaluations at least 4 weeks apart. Yet the primary response count and its denominator are not reported in the registry record. A detailed outcome definition cannot substitute for the observed endpoint data.

The design also illustrates why the comparison structure matters. This was a single-group study, with allocation listed as not applicable and masking listed as none. A response count in such a design can describe outcomes in the treated group, but there is no concurrently randomized group to support a direct treatment contrast. The inference is consequently narrower than in a randomized comparison.

Another statistical issue is the separation between enrollment and analysis. Enrollment is recorded as 18, but the registry does not report how many participants had evaluable response assessments or how missing assessments were handled. Readers need those details to understand the denominator and potential influence of incomplete follow-up.

The registry names multiple secondary outcomes but reports no analysis records. This makes multiplicity procedures, analysis populations and statistical methods unavailable for review. General statistical context: prespecified analysis methods and transparent outcome reporting help readers distinguish planned analyses from exploratory ones and interpret uncertainty appropriately. Their absence from the record should be treated as an information gap, not evidence of a particular method or result.

Finally, the safety figures distinguish serious from other adverse events but contain no event terms or detail. The record therefore demonstrates the value of reading counts in their reporting categories and recognizing what those counts do not describe. Together, these features make the study a useful case for separating design, endpoint definition, analysis reporting and causal interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting efficacy is that the registry record does not report the primary response count, an endpoint denominator or a confidence interval. It also does not report results for the named secondary outcomes. The outcome definitions and treatment schedule alone cannot show what was observed.

The study is single-group and unmasked, with allocation listed as not applicable. There is no concurrent control group in the registry design, so the record does not support a randomized comparison. General statistical context: in an uncontrolled design, observed outcomes may reflect influences other than the treatment, and the study cannot distinguish those influences through a between-group contrast.

Although enrollment is recorded as 18, the registry does not identify the analysis population or report how many participants were evaluated for each outcome. Missing-data handling, withdrawal information and endpoint-assessment completeness are not reported in the registry record. These gaps prevent assessment of whether incomplete follow-up could affect the reported outcome; no outcome result is reported to assess.

The record lists several secondary outcomes and no analysis records. It does not report statistical methods, multiplicity procedures, a sample-size justification, interim analyses or subgroup analysis methods. The planning assumptions described for illustrative calculations do not constitute the study's own design justification and do not describe its single-group structure.

Safety information is also limited. The registry records participants affected in serious and other adverse-event categories but does not provide serious-event terms or broader event details, follow-up duration for safety, or comparative safety data. These limitations are specific to what the registry record reports; unreported details should not be interpreted as evidence that an event or procedure did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma — NCT00398112.
• Registry record last updated 2014-05-14; status last verified 2012-12.
• Results first posted 2014-02-10.
• 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

NCT00398112 is a completed phase II, single-group study sponsored by the National Cancer Institute (NCI), with recorded enrollment of 18. The study examined oral sunitinib malate in patients with relapsed or refractory CLL or SLL. Treatment was scheduled daily on days 1-28, repeating every 28 days for up to 12 courses unless disease progression or unacceptable toxicity occurred.

The primary endpoint was the number of participants with confirmed CR or PR on two consecutive evaluations at least 4 weeks apart. The registry record does not report the primary endpoint result, its denominator, or results for the listed secondary outcomes. The record lists 0 participants affected by serious adverse events among 18 at risk, and 18 affected by other adverse events among 18 at risk; event details are not reported.

The recorded study start is 2007-08 and primary completion is 2008-11. Allocation is listed as not applicable, masking as none, and the model as single-group. The statistical analysis plan, missing-data procedures and analysis populations are not reported in the registry record.