Efficacy and Safety Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma (NCT01718691), a na phase 2 study. The primary outcome is Complete Response Rate (CR + CRu) Based on International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (1999)(IWRC).

2. Clinical Question

3. Trial Design

This was a phase II, multicenter, open-label clinical study of SyB L-0501 combined with rituximab. Its listed design is single group; allocation is NA and masking is none. These design features mean there is no randomized comparator arm in the registry record. The listed enrollment is 70, and the study status is completed. The record gives a start date of 2011-11 and a primary completion date of 2013-11.

The target population was untreated, low-grade B-cell non-Hodgkin's lymphoma and mantle cell lymphoma where hematopoietic stem cell transplantation was not indicated. The brief summary describes SyB L-0501 as two-day consecutive intravenous drip infusions at 90 mg/m2/day and rituximab as an intravenous drip infusion at 375 mg/m2. The arm is named as the combination, but a fuller arm description is not reported in the registry record.

The primary outcome was complete response plus unconfirmed complete response, assessed using the 1999 International Workshop response criteria, with a timeframe of up to 30 weeks. The record also lists response outcomes using revised malignant lymphoma criteria and WHO criteria, as well as progression-free survival, duration of response, and overall survival. The analysis methods and results for those outcomes are not reported in the registry record.

A single-group design can describe observed outcomes among participants receiving the combination, but it does not directly compare those outcomes with what would have occurred under another treatment. Open-label assessment can also leave room for knowledge of treatment to influence judgments, depending on how outcomes were assessed. Whether independent or blinded review was used is not reported in the registry record. A protocol, statistical analysis plan, sample-size justification, and interim-analysis details are also 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.

Population: Of the 70 subjects enrolled, one who did not receive the investigational product was excluded. Therefore, the total number of Baseline Participants is 69.

6. Primary Endpoint

The registry lists the primary outcome as Complete Response Rate (CR + CRu) Based on International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (1999)(IWRC), measured over Up to 30 weeks.

The primary endpoint is the percentage of participants with complete response (CR) or unconfirmed complete response (CRu), based on the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. The timeframe is up to 30 weeks. A response endpoint summarizes whether disease met specified response criteria at an assessment; it is not itself a direct comparison with another treatment.

Under the registry’s description, CR requires disappearance of detectable disease and reduction of lymph nodes larger than 1.5 cm to no larger than 1.5 cm. CRu includes a reduction in the sum of the products of the greatest diameters of lymph nodes larger than 1.5 cm by more than 75%, with an indeterminate bone marrow assessment. These definitions distinguish a complete response from an unconfirmed one while grouping both for the primary measure.

Response rates are used to describe antitumor activity at a specified assessment point. Their interpretation depends on the criteria, the timing and completeness of assessments, and the number of participants included in the analysis. General statistical point: a percentage is an estimate, and its uncertainty depends in part on the number of evaluable observations and the observed response frequency.

The registry record does not report the observed CR-plus-CRu count or percentage, a confidence interval, or the analysis population for this endpoint. Therefore, the endpoint definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

The study is listed as single group, with allocation marked NA and masking marked none. A single-group study can estimate outcomes observed among participants who received the combination. It cannot directly estimate a difference between the combination and a separate control treatment because no such arm is listed. In a randomized comparison, treatment groups are formed under an allocation process intended to make them comparable; that basis for a direct contrast is absent.

General statistical explanation: an observed outcome in one group can reflect treatment, the natural course of disease, participant selection, co-interventions, and measurement processes. Without a concurrent comparator, those contributions are difficult to separate. Historical or external comparisons can sometimes provide context, but they do not recreate random allocation and are vulnerable to differences between study populations or procedures. No external comparison is reported in the registry record.

What does a response percentage describe?

The primary measure is a percentage of participants meeting the CR-or-CRu definition under the International Workshop criteria, up to 30 weeks. It is a binary outcome at the participant level: the endpoint classifies a participant according to whether the response criteria were met. The record does not report the numerator, denominator used for the primary analysis, or resulting percentage. The 70 listed as enrollment should not be assumed to be the denominator for an outcome analysis; the analysis population is not reported in the registry record.

General statistical explanation: a confidence interval around a percentage conveys sampling uncertainty under its calculation method. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision. The interval does not address every possible source of bias, such as missing assessments or non-blinded evaluation. No confidence interval or method for calculating one is reported in the registry record.

Why do endpoint definitions matter?

Response outcomes depend on operational criteria. Here, the primary endpoint combines CR and CRu, with CR based on disappearance of detectable disease and specified lymph-node measurements. CRu includes lymph-node reduction and an indeterminate bone marrow assessment. The registry also lists response outcomes under revised malignant lymphoma criteria and WHO criteria. These are separate definitions, so their results, if available, should not be treated as interchangeable without examining the criteria and assessment procedures.

General statistical explanation: when multiple outcomes or definitions are examined, the chance of finding at least one apparently notable result can increase if interpretation focuses on whichever result looks most favorable. A prespecified primary endpoint can help focus interpretation, but the statistical plan and any approach to multiplicity are not reported in the registry record. The presence of multiple listed outcomes does not reveal how they were prioritized or analyzed.

What can the safety counts show?

The safety listing gives 69 participants at risk for serious adverse events and 9 affected, while the other-adverse-event listing gives 69 at risk and 69 affected. Serious adverse event terms include febrile neutropenia, tumour lysis syndrome, breast cancer, pneumonia cytomegaloviral, dermatitis allergic, and cytogenetic abnormality. Such summaries count recorded events or participants according to the registry’s categories; they do not establish a causal relationship with treatment. The record does not report a death count.

General statistical explanation: safety proportions can describe how often events were recorded in the observed group, but estimates may be imprecise, especially for less frequent events. A single-group safety summary also cannot determine how event rates compare with an untreated group or another regimen. The record does not report exposure-adjusted rates, detailed follow-up for safety, or attribution rules.

How should planning illustrations be read?

Any sample-size illustrations based on an observed effect are planning scenarios, not observed power and not evidence that the trial was designed around those assumptions. The stated illustration 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 outcomes, the illustration concerns total events; for other outcomes, it concerns participants per arm. These hypothetical two-arm planning assumptions do not change the actual single-group design of this study.

General statistical explanation: sample-size planning asks how much information a future study might need under specified assumptions. Power is a property of that design and assumed effect, not a measure of the probability that a result is true. Recalculations from posted summary statistics, if available, would be simple unadjusted calculations and may differ from a sponsor’s analysis. No sponsor analysis result is reported in the registry record, so no precedence question can be resolved from the available record.

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("Low-grade B-cell Non-Hodgkin's Lymphoma", "Mantle Cell Lymphoma")
n      <- c(59, 10)
events <- c(40, 7)
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  Low-grade B-cell Non-Hodgkin's Lymphoma  59  40  67.8  54.4  79.4  55.1  78.3  55.0  78.3
ARM  Mantle Cell Lymphoma  10  7  70.0  34.8  93.3  39.7  89.2  39.0  89.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary response endpoint and multiple additional outcomes. The secondary outcomes include response rates under other criteria, complete response measures, progression-free survival, duration of response, and overall survival. The record states 12 outcome measures, but the statistical analysis details for those measures are not reported in the registry record.

When a study examines several endpoints or definitions, multiplicity becomes relevant: a collection of tests can produce at least one apparently unusual result by chance more often than a single test, depending on the testing strategy. A prespecified hierarchy, adjustment, or other plan can guide interpretation. Whether any such strategy was used, and whether the primary endpoint was formally tested, is not reported in the registry record. No interim analyses or stopping rules are reported.

The record does not report how missing response assessments were handled, whether participants without an assessment were counted as nonresponders, or whether any imputation method was used. It also does not identify the primary analysis population or provide the number of participants evaluable for the primary endpoint. General statistical point: different missing-data assumptions can yield different response estimates, so the analysis rule matters alongside the endpoint definition.

Enrollment is listed as 70, whereas safety event summaries list 69 participants at risk. The record does not explain this distinction, and the safety denominator should not be assumed to define the efficacy analysis population. The record does not report a protocol-level sample-size justification or analysis plan. As a result, neither the handling of missing data nor the relationship between the registered endpoint and any final analysis can be assessed from the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (4.3%), tumour lysis syndrome (1.4%), breast cancer (1.4%), pneumonia cytomegaloviral (1.4%), dermatitis allergic (1.4%).

The registry lists 69 participants at risk for serious adverse events, with 9 affected. It separately lists 69 participants at risk for other adverse events, with 69 affected. These are safety summaries for the single treatment group. The record does not report a death count.

The listed serious adverse event terms and percentages are febrile neutropenia, 4.3%; tumour lysis syndrome, 1.4%; breast cancer, 1.4%; pneumonia cytomegaloviral, 1.4%; dermatitis allergic, 1.4%; and cytogenetic abnormality, 1.4%. The record does not state in this information whether participants could contribute more than one event term, so the listed terms should not be added together or treated as mutually exclusive categories.

General statistical explanation: an adverse event recorded during a study is not necessarily caused by the treatment. A single-group event summary describes what was reported among participants under observation, but without a control group it cannot establish how event frequency compares with another treatment or with background risk. The registry record does not provide detailed exposure duration, event-attribution rules, or a comparative safety analysis. The listed figures should therefore be read as descriptive counts and percentages, not as causal estimates.

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

The record establishes that the study was completed and identifies its primary question: the percentage of participants with CR or CRu under the International Workshop criteria, assessed up to 30 weeks. It also describes the population, combination treatment, single-group design, and selected safety counts. These registry entries clarify what the study was intended to assess.

The primary response result itself is not reported in the registry record. There is no observed response count or percentage, confidence interval, or test result in the record. Consequently, it is not possible to describe the observed primary endpoint magnitude or its precision. The absence of a result in this record is not evidence that no responses occurred; it means that the result is not reported in the registry record.

The study’s design also limits causal interpretation. A single-group, open-label study does not provide a randomized comparator for estimating how outcomes differ under another treatment. Descriptive outcomes from participants receiving the combination do not, by themselves, show what would have happened to comparable participants without it or under an alternative regimen. The record does not report blinded outcome review or methods that would otherwise establish a comparative effect.

Additional response definitions and survival outcomes are listed, but their results are not reported in the registry record. Nor are the analysis population, missing-data approach, multiplicity handling, or statistical analysis plan. The safety listing reports serious and other adverse events among participants at risk, but does not establish that the treatment caused those events or provide a comparative risk estimate.

General statistical point: an outcome estimate, its uncertainty, and the design supporting its interpretation are distinct pieces of evidence. A response percentage would describe observed activity under the stated criteria; a comparator would be needed for a direct treatment contrast; and analysis details would help assess how robust the estimate is to missing information and multiple outcomes. Since the registry record does not report the primary result or those analysis details, firm statistical conclusions about efficacy or comparative safety cannot be drawn from it.

14. Why This Trial Matters Statistically

Statistically, this study is useful to examine because it makes the distinction between an outcome definition and an outcome estimate clear. The registry record specifies a primary response endpoint and its assessment window, but does not report the observed response frequency or its uncertainty. A precise endpoint definition is necessary for interpretation, yet it cannot replace the result itself.

The design is also consequential. A single-group phase II study can describe outcomes among participants receiving the combination, but it does not create a randomized treatment contrast. This distinction helps prevent descriptive response or safety figures from being presented as comparative evidence. The open-label designation adds a further interpretive consideration: assessment could be influenced by treatment knowledge, although the registry record does not report whether independent or blinded review was used.

The record lists several response definitions and time-to-event outcomes. Multiple endpoints can be clinically and statistically informative, but their interpretation depends on prioritization, analysis methods, and missing-data handling. Those details are not reported in the registry record. The study therefore illustrates why readers need both outcome definitions and transparent reporting of analysis populations, estimation methods, and uncertainty.

Finally, the safety counts show why descriptive adverse-event summaries must be separated from causal claims. Events recorded during treatment are relevant observations, but a single-group record cannot establish whether treatment increased or decreased event risk relative to a comparator. The study matters statistically as an example of how design, endpoint choice, reporting completeness, and causal interpretation jointly determine what conclusions the record can support.

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 main limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It provides the CR-plus-CRu definition and the timeframe of up to 30 weeks, but not the observed count, percentage, confidence interval, or analysis population. Results for the additional response and survival outcomes are also not reported in the registry record.

The study is listed as single group, with allocation marked NA and masking marked none. No concurrent control group is listed, so the record does not support a direct randomized comparison. Open-label conduct can also affect outcome assessment, but whether an independent review process was used is not reported in the registry record.

The listed enrollment is 70, while safety summaries report 69 participants at risk. The reason for that difference is not reported in the registry record, and the safety denominator should not be substituted for an efficacy denominator. The record does not describe participant flow, withdrawals, treatment exposure, or how missing assessments were handled.

The registry lists several response criteria and other outcomes, but multiplicity procedures and the statistical analysis plan are not reported in the registry record. The protocol’s sample-size justification, interim analyses, analysis populations, and methods for time-to-event outcomes are also not reported. Safety details are limited to selected counts and listed serious event terms; the death count and detailed event attribution are not reported in the registry record. These gaps restrict assessment of both the magnitude and reliability of the study findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma — NCT01718691.
• Registry record last updated 2016-04-27; status last verified 2016-03.
• Results first posted 2016-04-27.
• 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

NCT01718691 is a completed, multicenter, open-label phase II study of SyB L-0501 plus rituximab in untreated, low-grade B-cell non-Hodgkin's lymphoma and mantle cell lymphoma where hematopoietic stem cell transplantation was not indicated. Its design is listed as single group, with allocation NA and masking none. Enrollment is listed as 70.

The primary endpoint is the percentage achieving CR or CRu under the International Workshop response criteria, up to 30 weeks. The record also lists response measures under revised malignant lymphoma and WHO criteria, plus progression-free survival, duration of response, and overall survival. The primary endpoint result, analysis population, confidence interval, and statistical analysis plan are not reported in the registry record.

Safety summaries list 9 participants with serious adverse events among 69 at risk, and 69 with other adverse events among 69 at risk. The death count is not reported in the registry record. The single-group design supports descriptive interpretation, not a direct randomized comparison.