Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia (NCT00098371), a na phase 2 study. The primary outcome is Complete Response (CR) Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study sponsored by the National Cancer Institute. The registry lists an enrollment of 64 and identifies the intervention as alvocidib, also known as flavopiridol. Allocation is listed as not applicable, and masking as none. These design features mean the record describes treatment in a single group rather than a randomized comparison. It cannot by itself separate changes during treatment from changes that might have occurred without the intervention or under another treatment.

The study concerned previously treated patients with B-cell chronic lymphocytic leukemia or prolymphocytic leukemia arising from CLL. The listed conditions also include refractory chronic lymphocytic leukemia. The registry’s official title specifies the loading dose and continuous infusion in previously treated patients. The treatment description schedules infusions on days 1, 8, 15, and 22, with courses repeating every 42 days for up to 6 courses unless disease progression or unacceptable toxicity intervened. Response assessments were planned after two, four, and six cycles.

The record lists a start date of 2005-04 and primary completion in 2009-06. Its status is terminated. The reason for termination, whether the full planned enrollment was treated or assessed, and the extent to which the treatment schedule was completed are not reported in the registry record. The listed enrollment should not be taken as the number included in the primary endpoint analysis.

The single-group design is important for interpretation. A response rate can describe outcomes among those assessed, but without a concurrent comparator it cannot establish how outcomes would have differed under another strategy. The registry record does not report a comparator-based effect estimate or an inferential analysis.

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

Analysis population for the primary outcome, as defined in the registry: Patients were assessed for clinical response after two, four and six cycles.

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 Complete Response (CR) Rate, measured over Up to 8 months.

The primary endpoint is the complete-response rate, expressed as a percent of patients, with a timeframe of up to 8 months. The registry defines complete response using a set of clinical, blood, and bone marrow conditions that must all be met for at least two months from completion of therapy. These include no lymphadenopathy in excess of 1 cm on physical examination, no hepatomegaly or splenomegaly on examination, and no constitutional symptoms. Blood-count requirements include polymorphonuclear leukocytes above 1500/µL, platelets above 100,000/µL, hemoglobin above 11.0 g/dl without transfusion, and a lymphocyte count below 5,000/µL. The bone marrow must be normocellular for age, with less than 30% of nucleated cells being lymphocytes, and without lymphoid nodules.

In general, a complete-response endpoint describes whether a participant meets a prespecified set of criteria, rather than measuring change in only one symptom or laboratory value. Requiring findings across several domains makes the endpoint a stringent classification of response under the registry definition. It does not, by itself, describe how long a response lasts beyond the required period or establish a comparative treatment effect.

The registry says that response was assessed after two, four, and six cycles. It does not report the number meeting the criteria, the denominator used for the rate, or a confidence interval. Therefore, the endpoint is defined, but its observed result cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is labeled phase II and single-group. The record identifies no randomized allocation and no masking. It lists complete-response rate as the primary endpoint, with the unit described as percent of patients and a timeframe of up to 8 months. It also lists 15 outcome measures and no analysis entries. A statistical analysis plan, the method used to calculate the primary endpoint, and any prespecified decision threshold are not reported in the registry record.

What does a response rate represent?

In general, a response rate is a proportion: the number meeting the outcome definition divided by the relevant analysis denominator. The denominator matters because it determines which participants contribute to the estimate. For a clinical study, the denominator might depend on whether participants started treatment, had an assessment, or met another analysis-population rule. Those rules are not reported in the registry record for this primary outcome. The listed enrollment of 64 cannot be substituted for an analysis denominator without evidence that all enrolled participants were included.

The primary outcome is described as a percent, but the registry does not post the numerator or the denominator for complete response. As a result, no response proportion can be interpreted or independently checked from this record. No recalculated result is available. There is also no stated sponsor analysis to compare with a recalculation.

Why does precision matter?

In general, an estimate based on a finite set of observations is subject to sampling uncertainty. A confidence interval expresses this uncertainty around an estimate under a specified statistical method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The interval does not account for every possible bias, and its interpretation depends on the method and assumptions used.

No confidence interval for complete response is reported in the registry record. The count of responses and analysis denominator are also absent, so neither the estimate nor its uncertainty can be derived. No p-value for the primary endpoint is reported. A p-value, in general, measures how unusual data would be under a specified null model; it is not a measure of the size or clinical importance of an effect. Here, neither the null model nor a primary-endpoint p-value is reported.

What does the design allow?

In general, a single-group study can describe outcomes observed during the study, subject to the endpoint definition and analysis population. It does not provide a concurrent randomized control group for estimating a between-group contrast. Differences from external experience or historical expectations would require additional information and assumptions; those comparisons are not reported in this registry record. Because allocation is listed as not applicable and the model as single group, a comparative interpretation is not supported by the design information recorded.

Masking is listed as none. In general, knowledge of treatment or assessment status can influence some measurements or judgments, depending on how an outcome is determined. The complete-response criteria include clinical examination and laboratory or marrow findings, but the registry does not report procedures intended to reduce assessment bias. This is a design consideration, not evidence that any assessment was biased.

How should planning illustrations be read?

The sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are described as participants per arm for non-time-to-event outcomes. These assumptions do not describe the actual single-group trial design, and the illustrations are not the trial’s original sample-size justification. They should not be interpreted as observed power. The protocol’s sample-size rationale and statistical plan are not reported in the registry record.

In general, a sample-size illustration asks how many participants a hypothetical future design might require under stated assumptions. It does not tell whether a completed study had adequate power after the fact, nor does it establish that an assumed effect is real. The listed two-arm assumptions are especially distinct from this single-group design. Since no primary response estimate is posted in the record, the result and its precision cannot be evaluated from the information given.

What does the assessment schedule imply?

The registry says clinical response was assessed after two, four, and six cycles. It also defines the primary timeframe as up to 8 months. In general, repeated assessments can describe whether response criteria are met at different points, but the analysis needs to specify which assessment is primary and how later or missing assessments are handled. The record does not report those details. The schedule alone cannot establish how many participants had an evaluable assessment or whether response was counted at a particular visit.

The registry lists pharmacokinetic, biological, and other clinical outcomes in addition to the primary endpoint. A statistical plan might address how these outcomes are analyzed and how multiple comparisons are considered, but that plan is not reported. The presence of multiple outcome measures does not by itself indicate that every outcome was formally tested or that a particular adjustment was used.

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("Treatment (Alvocidib)")
n      <- c(64)
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  Treatment (Alvocidib)  64  1  1.6  0.0  8.4  0.3  8.3  0.4  8.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the complete-response primary endpoint and secondary measures involving pharmacokinetics, laboratory and biological markers, and clinical comparisons. It reports no analysis entries. A multiplicity strategy, such as a prespecified hierarchy of outcomes or an adjustment to control the chance of false-positive findings across several tests, is not reported in the registry record. It is therefore not possible to determine whether or how multiplicity was addressed.

The absence of posted analyses should not be read as evidence that no analyses were conducted; it means the registry record does not contain analysis entries. Likewise, the list of outcome measures does not establish that all were measured, analyzed, or reported. The protocol’s statistical analysis plan is not reported in the registry record.

Missing data handling is also not reported. The record does not state how participants without an endpoint assessment were treated, whether incomplete evaluations were counted as nonresponses, or whether any imputation or sensitivity analysis was used. The enrollment figure of 64 does not establish the denominator for the primary endpoint. Nor does the assessment schedule after two, four, and six cycles establish that all enrolled participants completed those assessments.

In general, the handling of missing endpoint data can affect a response-rate estimate because the result depends on which participants are included and how unobserved outcomes are treated. A clear report would identify the analysis population, the number assessed, and the rule for participants with unavailable evaluations. Those details are not reported. Consequently, the primary result’s denominator, susceptibility to missing-data assumptions, and relationship to the planned assessments cannot be assessed.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (6.2%).

The registry’s adverse-event summary lists 64 at risk for both the serious and other adverse-event categories. It records 4 affected in the serious category and 64 affected in the other category. These are registry counts for the treatment group; they are not comparative estimates and do not establish that treatment caused each event. The summary’s top serious term is Infection, listed at 6.2%. The record does not provide further event-level detail in the registry record for this account.

The deaths field is not reported in the registry record. It should not be interpreted as a count of zero. The listed adverse-event figures also do not show duration, severity distribution beyond the serious classification, timing, or individual clinical context. Those details are not reported in the registry record.

In general, an at-risk count identifies the denominator used in an adverse-event summary, while an affected count identifies participants recorded as having an event in that category. These summaries should be interpreted using the registry’s category and reporting conventions. They are not a substitute for the primary complete-response result and cannot show comparative safety in a study without a control group.

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

The registry record establishes that a phase II, single-group study of flavopiridol was registered for previously treated patients with B-cell chronic lymphocytic leukemia or prolymphocytic leukemia arising from CLL. It specifies the treatment schedule and defines complete response using examination, symptom, blood-count, and bone marrow criteria. It also reports a clinical assessment schedule after two, four, and six cycles and posts some adverse-event counts.

What the record does not establish is the observed complete-response rate. The number of complete responses, the endpoint denominator, and a confidence interval are not reported in the registry record. Without those elements, there is no numerical primary result to interpret and no way to assess its precision. Enrollment of 64 is not a substitute for an analyzed denominator.

The design also does not provide a randomized comparator. In general, observed outcomes in a single group can describe what was recorded under the study conditions, but they cannot by themselves show how outcomes would compare under another treatment or no treatment. The record does not provide a comparative effect estimate.

The serious adverse-event summary reports 4 affected among 64 at risk and lists Infection at 6.2% among the top serious terms. Those figures describe the registry summary, not an estimate of risk relative to another intervention. The deaths field is not reported in the registry record, and no causal conclusion about individual events follows from the posted counts alone.

Thus, the record is informative about the study’s design, endpoint definition, planned treatment and assessment schedules, and selected safety reporting. It is insufficient to determine the primary response result, its uncertainty, or a causal treatment effect. The reason the study was terminated and the statistical analysis plan are also not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The registry supplies detailed criteria for complete response, including examination findings, symptoms, blood counts, and marrow status, as well as a requirement that the criteria hold for at least two months from completion of therapy. This makes the intended outcome understandable, but the definition alone cannot show how often it occurred.

The contrast between enrollment and analysis information is also important. The registry lists enrollment of 64, but does not report the primary endpoint denominator or number of complete responses. In general, readers need both to interpret a response proportion and judge its precision. Enrollment should not automatically be treated as the number assessed or analyzed.

The single-group design highlights a separate distinction: describing an outcome is not the same as estimating a comparative effect. Without a concurrent control group, the record cannot provide a randomized comparison against another treatment. This limitation remains even if a response estimate were available.

Finally, the record lists multiple outcome measures but no analysis entries or statistical plan. This leaves multiplicity, missing-data handling, analysis populations, and the methods for estimating the primary endpoint unclear. These are not minor reporting details: they shape how an estimate should be understood. The study therefore serves as a useful example of the difference between a registered endpoint definition and a fully interpretable statistical result.

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 statistical interpretation is that the registry record does not report the complete-response count, rate, analysis denominator, or confidence interval. Although the registry lists enrollment of 64, that figure does not establish the number included in the primary analysis. Without the outcome count and denominator, the main endpoint cannot be evaluated.

The design is single-group, with no randomized allocation and no masking. There is no like-for-like control comparison in the record. This constrains interpretation to description of outcomes in the treated group, if those outcomes are reported; it does not support a comparative treatment effect.

The registry gives the response criteria and assessment timing, but does not report the analysis population, the handling of missing assessments, or which assessment time point determined the primary result. The reason for termination and whether the planned treatment or assessment schedule was completed are not reported in the registry record. The stated enrollment should not be assumed to mean that all enrolled patients completed treatment or had evaluable outcomes.

The statistical analysis plan, multiplicity approach, and primary endpoint estimation method are not reported. Although 15 outcome measures are listed, no analysis entries are present. The record therefore does not show how secondary outcomes were analyzed or whether any adjustments or sensitivity analyses were used.

For safety, the record lists serious and other adverse-event counts and a top serious term, but the deaths field is not reported. The available summary does not provide comparative safety estimates or enough detail to infer causation. These limitations apply to interpretation of the registry record and should not be taken as evidence about unreported findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia — NCT00098371.
• Registry record last updated 2016-10-24; status last verified 2016-08.
• Results first posted 2016-10-24.
• 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 describes a phase II, unmasked, single-group study of flavopiridol, also called alvocidib, sponsored by the National Cancer Institute. It lists enrollment of 64, a start date of 2005-04, primary completion in 2009-06, and status as terminated. The study concerned previously treated patients with B-cell chronic lymphocytic leukemia or prolymphocytic leukemia arising from CLL.

The primary endpoint was complete-response rate up to 8 months, with clinical assessments after two, four, and six cycles. The registry defines the response criteria but does not report the number of responses, the analyzed denominator, or an estimated rate. It lists 15 outcome measures and no analysis entries.

The adverse-event summary records 4 serious-category affected among 64 at risk, 64 affected among 64 at risk in the other category, and Infection at 6.2% among the top serious terms. Deaths are not reported in the registry record. The reason for termination, statistical analysis plan, and missing-data methods are also not reported.