Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia (NCT01515176), a na phase 1, phase 2 study. The primary outcome is Number of Patients With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I).

2. Clinical Question

3. Trial Design

This was a Phase 1b/2 study of dinaciclib and ofatumumab for patients with relapsed or refractory CLL, SLL, or B-PLL. The registry lists the study as single-group, with no masking and allocation recorded as not applicable. Enrollment was 36. The sponsor was the National Cancer Institute (NCI). The study began in 2012-01, had primary completion on 2015-03-04, and is recorded as completed.

The intervention description identifies a treatment regimen containing intravenous ofatumumab and dinaciclib. Ofatumumab was scheduled on days 1, 8, 15, and 22 of courses 1–2 and on day 1 of courses 4–7. Dinaciclib began in course 2, with dosing on specified days in courses 2–7. The description says treatment repeats every 28 days, but the remaining schedule text is truncated. The full intended duration and details beyond the displayed schedule are not reported in the registry record.

The safety record separates participants by Dose Level I and Dose Level II. The registry does not describe a randomized allocation between those dose levels, so their listed safety counts are descriptive rather than a controlled comparison. The record does not report the rules used to assign participants to dose levels, the dose-escalation procedure, or a dose-selection result.

The primary endpoint is a count of participants with dose-limiting toxicity incidents, assessed up to day 56. The study also names complete response rate, overall survival, progression-free survival, and time to treatment failure as secondary outcomes. Although the registry lists seven outcome measures, it does not report the primary endpoint result or results for those secondary outcomes. The registry lists no analyses. A planned sample-size justification and a detailed statistical analysis plan 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 With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I), measured over Up to day 56.

The primary endpoint is the number of participants with dose-limiting toxicity incidents graded according to NCI CTCAE version 4.0, with assessment up to day 56. The registry description distinguishes hematologic toxicities from non-hematologic toxicities. Hematologic assessment uses continuous measures, primarily nadir and percent change from baseline, alongside categorization by CTCAE toxicity grade. Non-hematologic examples named in the record are dyspnea and renal toxicities, assessed using ordinal CTCAE grading.

In general, a dose-limiting toxicity endpoint is used in early-phase studies to characterize whether treatment-related toxicity constrains administration of a regimen or dose. Counting participants with an event gives a direct summary of how many experienced a qualifying toxicity under the endpoint definition. It does not by itself describe every adverse event, its duration, severity distribution, or causal relationship to treatment.

The registry record does not report the observed primary endpoint count, the number assessed for this endpoint, or the detailed operational criteria defining which toxicities qualified as dose-limiting. It therefore does not allow a reader to determine the recorded incidence of dose-limiting toxicity from the primary outcome listing alone. Nor does the endpoint establish comparative safety, because the study is identified as single-group and no randomized control group is listed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design permit?

The registry identifies this study as single-group, with allocation marked not applicable and masking absent. In a single-group study, outcomes are observed among people receiving the study regimen rather than compared through randomized assignment to a control regimen. This can support descriptive reporting of safety and activity in the enrolled group, but it does not isolate the effect of treatment from other possible influences. Differences between Dose Level I and Dose Level II cannot be interpreted as randomized treatment contrasts because the registry does not describe random assignment to those groups.

In general, randomization helps balance measured and unmeasured factors between groups on average. Without a randomized comparator, observed differences across groups may reflect factors other than dose. The record does not state how participants entered each dose level or whether the groups were intended for a formal between-group analysis. The dose-level safety figures should therefore be read as separate descriptive listings, not as evidence from a controlled comparison.

What does a participant count convey?

The primary endpoint is expressed as a count of participants with dose-limiting toxicity incidents. A count communicates the number meeting the endpoint definition, but interpretation also depends on how many participants were evaluated and whether all participants had comparable follow-up and assessment. The registry lists the endpoint timeframe as up to day 56, but does not report the number assessed, the endpoint count, or missingness for this outcome. No incidence estimate or confidence interval for the endpoint is reported in the registry record.

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; it does not guarantee that the true value lies within the interval. Because no primary endpoint estimate or interval is posted in the registry record, the precision of the toxicity finding cannot be judged from the outcome listing.

How are the toxicity grades used?

The endpoint description says hematologic toxicities are assessed using continuous measures, primarily nadir and percent change from baseline, as well as CTCAE version 4 toxicity categories. Continuous measures preserve information about observed laboratory values and their change, whereas grading groups observations into ordered severity categories. Non-hematologic dose-limiting toxicities, including dyspnea and renal toxicity examples, are described as assessed using ordinal CTCAE grading only.

In general, an ordinal scale preserves the ordering of categories but does not imply that the distance between adjacent categories is equal. Continuous measurements and ordered categories can provide complementary descriptions, but they answer different questions. The registry does not specify how the continuous measures and toxicity grades were combined to determine whether an incident qualified as dose-limiting. It also does not provide the detailed threshold rules or adjudication process. Those operational details are not reported in the registry record.

What does the safety listing mean?

The registry safety entries report participants at risk and participants affected, separated into serious and other adverse events for each dose level, alongside deaths. These are descriptive safety summaries. In general, a participant count for an adverse-event category is not the same as an event count: a participant may experience more than one event, and the listing may count affected participants rather than all episodes. The record labels the columns as affected participants, so the figures should not be recast as numbers of individual event episodes.

The registry also lists selected serious adverse-event terms with percentages. The record does not provide the denominator, event-counting convention, or details about overlap among participants for these percentages. They should be reported as listed rather than used to calculate comparisons or infer a rate for a different population. Safety observations in a single-group study also do not establish whether an event is attributable to the treatment. Attribution, timing, and clinical context are not provided for the listed terms.

How should the planning illustrations be interpreted?

Sample-size figures associated with the analysis are planning illustrations computed from an observed effect, not the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the displayed quantity is a total number of events; other calculations are participants per arm.

In general, planning calculations ask how much information a future study might need to detect a specified effect under stated assumptions. They depend on the effect size, variability or event frequency, allocation, and statistical method. An illustration based on an observed effect is sensitive to uncertainty in that effect and should not be read as a design feature of the completed trial. It is not observed power, and it does not show the probability that the treatment works. The registry record does not report a protocol-based sample-size justification for this study.

The record lists 36 participants enrolled, but that enrollment count is distinct from any hypothetical participant requirement in a planning illustration. The study is single-group, whereas the illustration’s assumptions specify equal allocation between two arms. Such assumptions describe a hypothetical comparative design, not the actual allocation structure recorded for this trial. No recalculated treatment comparison is available in the registry record, and no sponsor analysis is reported there.

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("Dose Level I: Treatment (Ofatumumab, Dinaciclib)", "Dose Level II: Treatment (Ofatumumab, Dinaciclib)")
n      <- c(4, 32)
events <- c(0, 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  Dose Level I: Treatment (Ofatumumab, Dinaciclib)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Level II: Treatment (Ofatumumab, Dinaciclib)  32  0  0.0  0.0  10.9  0.0  10.7  0.1  10.6

11. Multiplicity, Missing Data and Analysis Populations

The registry names several secondary outcomes: complete response rate, overall survival, progression-free survival, and time to treatment failure. It does not report results for these outcomes or describe how they were analyzed. It also does not state whether any adjustment for multiple outcomes or multiple statistical tests was planned. Multiplicity matters because evaluating several outcomes can increase the chance of at least one apparently noteworthy result when each is considered separately. Without a reported testing strategy, no conclusion about multiplicity control is possible.

The registry lists seven outcome measures and no analyses. A count of registered outcome measures does not identify which outcomes were analyzed, how endpoints were operationalized, or which analysis populations were used. The record does not report a statistical analysis plan, analysis sets, handling of missing observations, censoring rules for time-to-event outcomes, or sensitivity analyses. Those details are not reported in the registry record.

Missing outcome data can affect interpretation when people with incomplete follow-up differ from those with observed outcomes. In general, the consequences depend on why information is missing and on the analysis method. The registry does not report missing-data counts or methods for the primary endpoint or secondary outcomes, so the extent and handling of missing data cannot be assessed.

The study is recorded as single-group, and no randomized comparator is listed. Consequently, any planning illustration that assumes equal allocation between two arms describes a hypothetical design rather than the trial’s own analysis. The registry does not report whether interim analyses were planned or conducted, or how any such analyses would have affected inference.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypophosphatemia (37.5%), leukocytosis (25.0%), pleural infection (25.0%), lymphocyte count decreased (25.0%), lung infection (12.5%).

The registry lists serious and other adverse-event counts separately for Dose Level I and Dose Level II. For Dose Level I, 4 participants were listed at risk for serious events and 3 were affected; 4 were at risk for other events and 4 were affected. The death count was 0. For Dose Level II, 32 were listed at risk and 32 affected for both serious and other events; the death count was 1. These are registry safety counts, not the primary dose-limiting toxicity result.

The serious-event terms listed with percentages are hypophosphatemia, 37.5%; leukocytosis, 25.0%; pleural infection, 25.0%; lymphocyte count decreased, 25.0%; lung infection, 12.5%; and sepsis, 9.4%. The registry does not state the denominator or whether the percentages refer to participants or events. It is also not clear whether individuals could appear under multiple terms. The percentages should therefore be read as reported, without deriving additional rates or comparisons.

In general, an adverse event occurring during a study does not by itself establish that treatment caused it. The registry entries do not give causal attribution or event-level clinical context. The single-group design also provides no randomized safety comparator.

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

The record describes a completed Phase 1b/2 study of dinaciclib with ofatumumab in relapsed or refractory CLL, SLL, or B-PLL, with enrollment of 36. Its primary outcome is a dose-limiting toxicity count through day 56. The registry describes toxicity assessment methods and posts safety listings for Dose Level I and Dose Level II. It does not report the observed primary endpoint result, so the central toxicity outcome cannot be quantified from the posted primary outcome information.

The registry also names complete response rate, overall survival, progression-free survival, and time to treatment failure. Their results are not reported in the registry record. Without those results, the record cannot establish the level of response or the time-to-event outcomes among participants. It also does not report a comparative treatment effect because the study is listed as single-group with no randomized comparator.

The posted safety counts and serious-event terms offer descriptive information about events recorded by dose level. They do not establish that treatment caused an event, and the registry does not provide enough detail to infer the clinical context or compare the listed percentages reliably. The safety listings are not interchangeable with the dose-limiting toxicity endpoint, which has its own stated assessment criteria.

In general, an early-phase study may characterize a regimen and inform later research, but its design and reporting determine what can be concluded. A single-group record can describe observations in participants receiving treatment, but cannot by itself distinguish treatment effects from other explanations. The record does not report a dose-selection conclusion, a statistical analysis plan, or a protocol-based sample-size justification. Accordingly, the posted information supports a description of the trial’s design and recorded safety entries, but not a conclusion about comparative efficacy, a definitive benefit-risk balance, or the treatment’s effect relative to another approach.

14. Why This Trial Matters Statistically

This trial is statistically notable for combining an early-phase toxicity question with secondary outcomes that span response and time-to-event measures. The primary endpoint is a participant count for dose-limiting toxicity incidents, graded according to NCI CTCAE version 4.0 and assessed up to day 56. The endpoint description also distinguishes hematologic measures from non-hematologic ordinal grading. That illustrates why an endpoint’s operational definition matters: the reader needs to know which events qualify, how grading is applied, and how observations are summarized.

The registry record makes the limits of interpretation especially visible. The study is single-group, and the safety listings distinguish Dose Level I from Dose Level II without describing random assignment. Those group counts can be reported descriptively but do not create a randomized dose comparison. The registry also names several secondary outcomes while reporting no analyses or outcome results. Thus, having an outcome listed is not equivalent to having an interpretable estimate posted.

In general, complete reporting of denominators, analysis populations, missing-data handling, endpoint definitions, and uncertainty estimates helps readers assess both magnitude and precision. A count without an endpoint result, assessed denominator, or interval cannot fully communicate uncertainty. Likewise, serious-event percentages without a stated denominator limit interpretation. These are not reasons to infer an unreported result; they identify what information would be needed for a fuller statistical reading.

The record’s planning assumptions also illustrate a distinction between trial design and later planning exercises. A hypothetical calculation using equal allocation between two arms does not describe this single-group trial. Planning figures are not observed power and do not repair missing outcome reporting. Keeping these distinctions clear helps prevent descriptive safety entries, hypothetical design calculations, and unreported efficacy outcomes from being conflated.

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 endpoint result is not reported in the registry record. The record therefore does not give the number of participants meeting the dose-limiting toxicity definition or the number assessed. Although the endpoint timeframe and broad assessment approach are described, detailed qualification criteria and the method for combining continuous laboratory measures with toxicity grades are not reported.

The safety record provides counts by dose level, but does not describe allocation to those levels or establish a randomized comparison. The registry does not report the denominator or calculation basis for the selected serious-event percentages, nor does it provide event-level timing, attribution, or clinical context. The counts should not be interpreted as evidence of causation or as a controlled safety contrast.

The record lists secondary outcomes but does not report their results. It also lists no analyses, and does not report the statistical analysis plan, analysis populations, missing-data methods, censoring rules, or multiplicity approach. The enrollment count of 36 does not supply those missing details or establish how many participants contributed to each outcome.

The treatment schedule description is truncated, so the full regimen duration and schedule are not available in the registry text. The dose-escalation procedure and the rationale for dose levels are not reported. A protocol-based sample-size justification and any interim-analysis plans are also not reported in the registry record. Together, these omissions restrict assessment of endpoint precision, analysis choices, and the extent to which the posted summaries represent the intended study procedures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia — NCT01515176.
• Registry record last updated 2018-03-15; status last verified 2018-02.
• Results first posted 2018-03-15.
• 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

This completed Phase 1b/2 study evaluated dinaciclib with ofatumumab in relapsed or refractory CLL, SLL, or B-PLL. It was recorded as single-group, unmasked, and without applicable allocation, with 36 participants enrolled. The sponsor was the National Cancer Institute (NCI); the study began in 2012-01 and reached primary completion on 2015-03-04.

The primary endpoint was the number of participants with dose-limiting toxicity incidents graded according to NCI CTCAE version 4.0, assessed up to day 56. The record describes assessment of hematologic and non-hematologic toxicities but does not report the primary endpoint result. Secondary outcomes include complete response rate, overall survival, progression-free survival, and time to treatment failure; their results are not reported in the registry record.

Safety listings provide counts by Dose Level I and Dose Level II and selected serious-event terms with percentages. These are descriptive entries, not a randomized comparison. The registry lists no analyses and does not report a detailed statistical analysis plan, missing-data methods, or a protocol-based sample-size justification.