Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (NCT02100423), a na phase 2 study. The primary outcome is Overall Response Rate Based on NCI-WG (for CLL) and Cheson Criteria (for SLL).

2. Clinical Question

3. Trial Design

This was a phase II, single-group study with an enrollment of 35 participants. The registry lists the study status as completed. Its start date is 2014-10-16, and its primary completion date is 2018-04-04. These dates describe the study record, but do not establish when each participant began or ended treatment.

The intervention was a combination of curcumin and cholecalciferol. Participants took curcumin by mouth daily on days 1-28 of each course. Cholecalciferol was taken by mouth daily on days 8-28 of course 1 and days 1-28 of later courses. Courses were scheduled every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. The record also lists laboratory biomarker analysis and a pharmacological study as interventions, but does not report their specific procedures or findings.

Because the study is single-group, its primary response endpoint is an observed outcome in participants receiving the combination, not a comparison between assigned treatment groups. Allocation is recorded as NA and masking as none. The registry record does not describe a control arm, random assignment, or blinding. Results from a single group cannot by themselves separate an intervention-associated outcome from the effects of patient characteristics, disease course, assessment procedures, or other factors.

The primary endpoint timeframe is up to 2 years. The registry also lists time to first cytotoxic treatment, progression-free survival, overall survival, and duration of response as secondary outcomes. It does not report analysis results for these outcomes. The exact follow-up schedule, handling of treatment discontinuation, and rules for evaluating participants who did not complete planned courses 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants enrolled in 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.

Population: Participants enrolled in study

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate Based on NCI-WG (for CLL) and Cheson Criteria (for SLL), measured over Up to 2 years.

The primary endpoint is overall response rate (ORR), defined in the registry record as the percentage of participants with a biologic response, complete response (CR), or partial response (PR). CLL response was to be assessed using NCI-WG criteria, and SLL response using Cheson criteria. The stated timeframe is up to 2 years. The record also describes response timing as running from the first recorded CR or PR, whichever comes first, until recurrent or progressive disease is objectively documented and assessed.

In general, a response endpoint summarizes the proportion of participants who meet prespecified disease-response criteria during an observation period. It can be useful in a phase II study as a way to describe observed activity, particularly when there is no comparator group. It does not, on its own, quantify a difference from another treatment or establish why a response occurred.

The registry record says that the point estimate and 95% confidence interval were to be calculated using binomial distribution theory. A confidence interval describes the uncertainty around an estimated response proportion: a narrower interval indicates greater precision, while a wider interval indicates less precision. However, the observed ORR and its confidence interval are not reported in the registry record. Without those results, the endpoint's observed magnitude and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage: the proportion of participants classified as having a biologic response, complete response, or partial response. The registry specifies NCI-WG criteria for CLL and Cheson criteria for SLL, and gives a timeframe of up to 2 years. It says the response-rate point estimate and 95% confidence interval would be calculated using binomial distribution theory. The observed estimate and interval are not reported in the registry record.

What does a response proportion describe?

In general, a proportion is formed by identifying participants who meet a defined outcome and relating that count to a defined participant group. For a response endpoint, the classification rules matter: they determine which observations count as biologic response, CR, or PR. A proportion describes the frequency of those classifications in the group analyzed. It does not by itself describe a treatment contrast or explain why participants met the criteria.

The denominator also matters. The primary endpoint description identifies the population as participants enrolled in the study, but detailed analysis-population rules are not reported in the registry record. It is therefore not possible to establish from this record how missing assessments, early discontinuations, or other incomplete follow-up would be handled in the response calculation. In general, changing which participants are included can change both the estimate and its interpretation.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty associated with an estimate. A point estimate gives one summary of the observed data; the interval indicates a range of values compatible with the data and the method's assumptions. An interval is not a guarantee that the true value lies within its endpoints, nor does it correct problems caused by an unsuitable design or incomplete outcome reporting. Here, the planned interval method is identified, but the interval itself is not reported in the registry record.

For a binary outcome such as response classification, binomial methods model each participant's outcome as belonging to one of two categories for the calculation. The registry specifically names binomial distribution theory. In general, the statistical properties of a proportion estimate depend on the number of participants and the number classified as having the event. No response count is reported, so neither the estimate nor its uncertainty can be reconstructed from the registry entry.

Why does the single-group design matter?

In general, a single-group study estimates outcomes within the group receiving the intervention. It does not directly estimate the difference between that group and a concurrent control group. Even a precisely estimated response proportion would remain a within-group result. Differences in disease characteristics, assessment timing, natural disease course, or other factors cannot be separated from an intervention effect using a randomized comparison when no comparison group is described.

The record lists allocation as NA, masking as none, and the model as single group. Thus, there is no indication of randomized assignment or masking in this record. These design details should be kept distinct from the planned method for calculating a response proportion: an interval can quantify sampling uncertainty for a within-group estimate, but it cannot substitute for a comparator or remove design limitations.

How should the sample-size illustrations be understood?

In general, power calculations are planning tools that describe the sample size associated with specified assumptions about an effect, significance level, allocation, and statistical method. They do not show that a study had a particular probability of detecting an effect after its results are known. The record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. Those assumptions describe illustrations, not the actual single-group design, which has no two-arm allocation.

Sample-size illustrations are not observed power and do not report trial outcomes. The record does not give numerical planning estimates in the registry record described for this analysis. It also does not report the trial's own sample-size justification. In general, planning calculations depend on the chosen target effect and assumptions; changing those assumptions changes the resulting planning requirement. The illustrations should therefore not be treated as evidence that the trial was adequately powered for its endpoint.

What other analysis details are missing?

The registry record reports zero analyses. Beyond the stated binomial approach for the primary response estimate, the full statistical analysis plan is not reported in the registry record. In particular, the record does not specify detailed rules for missing response assessments, analysis populations, covariate adjustment, or the handling of multiple outcomes. These omissions prevent a complete audit of how the planned endpoint would be translated into an analysis. They do not justify filling in methods based on common practice; the interpretation should remain limited to the methods explicitly described.

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 (Curcumin, Cholecalciferol)")
n      <- c(35)
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  Treatment (Curcumin, Cholecalciferol)  35  0  0.0  0.0  10.0  0.0  9.9  0.1  9.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response endpoint and several secondary outcomes: time to first cytotoxic treatment, progression-free survival, overall survival, and duration of response. It also reports six outcome measures in total. Listing multiple outcomes creates a general statistical consideration: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can address this by adjusting interpretation or testing, but the choice depends on the analysis plan and the inferential goals.

A multiplicity adjustment, testing hierarchy, or prespecified strategy for interpreting the outcomes is not reported in the registry record. The record reports zero analyses, so it does not provide outcome-specific estimates or p-values to evaluate. The primary endpoint description does state that a 95% confidence interval would be calculated using binomial distribution theory; it does not describe how that interval would relate to inference across the other outcomes.

Missing-data methods and detailed analysis populations are also not reported in the registry record. The primary endpoint population is described as participants enrolled in the study, but this does not fully specify how participants with no evaluable response assessment would be handled. Follow-up rules for the secondary outcomes, censoring procedures, and any sensitivity analyses are not reported in the registry record.

In general, these details matter because exclusions, incomplete observation, and outcome selection can affect the interpretation of estimates. The available record supports identifying the planned outcome areas and the stated primary endpoint method, but it does not support reconstructing a complete statistical analysis plan or determining how missingness and multiplicity were handled.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (2.9%).

The registry reports one participant with a serious adverse event among 35 at risk in the treatment group. It separately reports other adverse events in 33 participants among 35 at risk, and records one death. Diarrhea is listed as the top serious adverse-event term at 2.9%. These are separate registry summaries; the record does not explain whether individual events overlap across categories or provide fuller event-level descriptions.

In general, a participant count indicates how many people in the listed group were recorded as having an event, while an event count may include multiple events in the same person. The record labels the serious and other categories as participant counts at risk and affected. It does not give detailed timing, severity grades beyond the serious-event classification, relatedness assessments, or a comparison group. Those details are not reported in the registry record.

One recorded death is a count, not by itself evidence that treatment caused the death. Likewise, the listed serious-event term and percentage should be read as registry safety information, not as a comparative estimate. With a single treatment group, the record does not provide a like-for-like control estimate against which these counts could be compared.

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

The registry record identifies a phase II study of curcumin plus cholecalciferol in previously untreated stage 0-II CLL or SLL. It describes the treatment schedule, a primary response endpoint, and selected safety counts. It also lists secondary outcomes. These details establish what the study set out to examine and what kinds of results the registry records, but they do not supply a primary response result.

The primary endpoint was overall response rate under NCI-WG criteria for CLL and Cheson criteria for SLL, with a stated timeframe of up to 2 years. The planned estimate was to include a 95% confidence interval based on binomial distribution theory. The observed response proportion and confidence interval are not reported in the registry record. The record therefore does not show the frequency of response or how precise an estimate would be.

Even if a response proportion were available, the single-group design would make it a description of outcomes in the treated group rather than a randomized comparison. In general, an outcome observed after an intervention is not, on its own, proof that the intervention caused that outcome. A comparator is needed to estimate a between-group contrast under a defined design. No comparator group is described in this study record.

The safety counts provide a limited description of recorded events in the treatment group. They do not establish causation or allow comparison with an alternative group. Similarly, the listed secondary outcomes are not results: their estimates and analyses are not reported in the registry record. The record also does not report detailed analysis-population rules, missing-data handling, or a complete statistical analysis plan.

The defensible interpretation is therefore bounded. The registry documents a completed, single-group phase II trial with enrollment of 35 participants, a specified regimen, and a planned response endpoint. It does not report the efficacy estimate needed to characterize the primary outcome, nor comparative evidence to estimate a treatment difference. No conclusion about comparative benefit or harm can be drawn from the information in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the reported result must be read together. The study is a phase II single-group investigation, with 35 participants enrolled and a response endpoint defined for CLL and SLL. Its record describes a planned proportion estimate and confidence interval, but does not report either the observed response rate or the interval. Without those results, the central quantitative endpoint cannot be interpreted.

In general, a confidence interval helps show how precisely a proportion has been estimated, while a comparator helps address a different question: how outcomes differ between groups. These are not interchangeable. A confidence interval around a single-group response rate would describe uncertainty around that group's estimate; it would not create a treatment comparison. The absence of a comparator is especially important when readers are tempted to interpret a response outcome as evidence of a causal effect.

The record also shows why a list of outcome names is not a substitute for analysis results. Time to first cytotoxic treatment, progression-free survival, overall survival, and duration of response are listed, but their findings are not reported in the registry record. The safety summaries likewise require context: counts describe recorded events, but a single-group record cannot provide a comparative event rate.

Finally, the record distinguishes study planning from observed evidence. Sample-size illustrations based on assumptions are not observed power and do not tell readers whether the trial's actual design was sufficient for its primary question. The trial's own sample-size justification is not reported in the registry record. Together, these features make transparent outcome reporting and clear analysis details central to interpreting what the study can contribute statistically.

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 principal limitation for statistical interpretation is that the registry record does not report the primary response estimate or its 95% confidence interval. It states the endpoint definition and planned method, but provides no observed response count or proportion. As a result, the magnitude and precision of the primary outcome cannot be assessed from this record.

The study is single-group, with allocation recorded as NA and masking as none. There is no comparator described, so the record does not support a randomized between-group estimate. Any outcome in the treated group would be descriptive rather than a direct estimate of a treatment contrast. This design also limits interpretation of the safety summaries as comparative risks.

The registry lists secondary outcomes, but their results are not reported in the registry record. It also reports zero analyses. Details on analysis populations, missing assessments, censoring, multiplicity, and sensitivity analyses are not reported in the registry record. These gaps mean the analysis approach cannot be fully assessed beyond the stated binomial method for the primary response estimate.

Enrollment was 35, but enrollment alone does not disclose the number with evaluable response assessments or the amount of follow-up for each outcome. The record does not report subgroup counts or participant characteristics needed to assess how the enrolled group was composed. The study's own sample-size justification is not reported in the registry record. These limitations are specific to interpreting the posted registry information; they do not establish that unreported analyses were or were not performed outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma — NCT02100423.
• Registry record last updated 2024-04-12; status last verified 2024-03.
• Results first posted 2024-04-12.
• 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

NCT02100423 is a completed phase II, single-group study of curcumin and cholecalciferol in previously untreated stage 0-II CLL or SLL. Enrollment was 35. Curcumin was taken daily by mouth, with cholecalciferol added according to the course-specific schedule, for up to 6 courses unless progression or unacceptable toxicity occurred.

The primary endpoint was overall response rate under NCI-WG criteria for CLL and Cheson criteria for SLL, with a timeframe of up to 2 years. The registry describes a binomial estimate and 95% confidence interval but does not report the result. Secondary outcomes are listed without results. Safety information includes one participant with a serious adverse event, 33 with other adverse events, and one death. The single-group design does not provide a comparator for estimating treatment differences.