Oncaspar/Doxil/Decadron in Patients With Refractory Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oncaspar/Doxil/Decadron in Patients With Refractory Lymphoid Malignancies (NCT00837200), a na phase 2 study. The primary outcome is Tumor Response.

2. Clinical Question

This is an exploratory Phase II pilot study, not a randomized comparison of ODD with another treatment. Its clinical question is therefore about the response observed during treatment in this enrolled group, rather than a comparative treatment effect. The population description emphasizes refractory disease and allows unlimited prior regimens, while the listed conditions and the broader eligibility description are not identical in scope. The registry record does not give a separate analysis of results by malignancy type, prior treatment history, or other participant characteristics. Consequently, the primary question concerns the overall response measure as defined in the record, and the available record does not show whether responses differed across disease groups.

3. Trial Design

The registry describes a Phase II pilot efficacy trial of Oncaspar, Doxil, and Decadron in patients with refractory lymphoid malignancies. Its design is single group, with allocation recorded as not applicable and masking recorded as none. There is no concurrent control arm, so outcomes cannot be interpreted as a randomized comparison with another regimen or with usual care.

The record lists an enrollment of 13. Treatment was described in 28-day cycles. Oncaspar and Doxil were scheduled on days 1 and 15, while Decadron was scheduled on days 1, 8, 15, and 22. The treatment description says therapy would continue until disease progression or unacceptable side effects. The brief summary also describes clinical evaluation before each cycle and disease assessments every 2 cycles. The record says responding patients who were candidates for allogenic stem cell transplantation could proceed to conditioning chemotherapy and transplant after 4 cycles.

Assessments were tailored to disease type. The record describes blood counts and imaging for leukemia, imaging for lymphoma, and tumor markers and other disease assessments for multiple myeloma. These differences matter when interpreting a pooled tumor-response outcome: assessment procedures were not identical across the malignancies included.

The study status is terminated. The recorded start is 2009-03, and primary completion is recorded as 2011-01. The registry record does not explain the reason for termination or report whether the planned enrollment was reached. It also does not report a protocol-based sample-size justification, interim analysis plan, or detailed statistical analysis plan.

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 Tumor Response, measured over 16 weeks.

The primary endpoint is tumor response, measured as the number of participants meeting the response definition at 16 weeks. The registry defines complete response as resolution of detectable clinical or radiographic disease, disappearance of disease-related symptoms, and normalization of biochemical abnormalities for at least 6 weeks following treatment, with no bone marrow infiltration. Partial response requires reduction of measurable lesions by 50% or more and no new lesions. Stable disease is defined as not meeting partial-response criteria and showing no evidence of progression; stable disease lasting more than 2 months was also counted as a response.

As a general statistical concept, a binary response endpoint reduces each participant’s outcome to whether the defined response criterion was met. This can make a complex clinical assessment easier to summarize, but the result depends on the definitions, timing, and assessment procedures used. Here, the registry’s response rules incorporate clinical, imaging, laboratory, and disease-specific assessments. Because those procedures vary by malignancy, a single response count may combine assessments that are not identical across participants.

The endpoint is distinct from a measure of how long response lasts or how long participants remain alive without progression. Although disease progression is mentioned in the treatment description, the primary endpoint is the response status at the specified assessment time. The registry record does not report the number of participants meeting the primary response definition or a statistical estimate of the response rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods interpretation starts with distinguishing the study design from the endpoint. This trial is recorded as single group, with no masking and no allocation to different study arms. The primary outcome is a participant-level tumor-response classification at 16 weeks. The record’s endpoint type is a count of participants, which means the intended summary is based on how many people meet the response criteria. The registry record does not report the actual primary count or an analysis of it.

What does a single-group design allow?

As a general statistical principle, a single-group study can describe what happened among the participants who received the intervention. It does not create a randomized contrast against a control group. Randomization is commonly used to make treatment groups comparable, on average, with respect to factors that could affect outcomes. No such between-group comparison is available in this record. Therefore, even if an outcome count were reported, it would describe the enrolled group and would not alone show what would have happened to comparable participants without ODD or with another treatment.

The absence of masking is also relevant in general. Knowledge of treatment can potentially affect how symptoms are reported, how assessments are conducted, or how borderline outcomes are classified. The record does not describe safeguards that might address these possibilities, so their use is not reported in the registry record.

How should a binary response be understood?

In general, a binary outcome assigns each participant to one of two categories, such as meeting or not meeting a response definition. A count can be useful for communicating how many participants had the defined outcome. Its interpretation depends on the endpoint rules and on complete, consistent outcome ascertainment. The tumor-response definition combines several criteria and disease-assessment methods. Complete response, partial response, and stable disease lasting more than 2 months are treated as responses according to the record. The registry does not provide a breakdown of the primary outcome across those categories, or explain how missing or unevaluable assessments were handled.

A confidence interval, as a general concept, expresses uncertainty around an estimated quantity. It can show how much precision is supported by the observed data under the statistical method used. No confidence interval for the primary response outcome is reported in the registry record. A hypothesis test would address a specified statistical question, but no primary-outcome test or analysis is reported. The registry indicates 0 posted analyses; it does not provide an analysis plan or explain whether analyses were conducted outside the registry record.

What do the planning illustrations represent?

Any sample-size illustrations associated with the posted results are planning calculations, not outcomes observed in this trial. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. Those assumptions describe a hypothetical two-arm planning setup, whereas this study is recorded as single group. The illustrations therefore do not establish the trial’s original design rationale or its power. The registry record does not report the trial’s own sample-size justification. A planning sample size is not observed power and should not be interpreted as evidence that the trial did or did not detect an effect.

In general, power is a design property conditional on assumptions about the effect, variability, allocation, and analysis. It is not a retrospective measure of whether a study’s result is convincing. Because the primary response result and a trial-specific statistical plan are not reported in the registry record, no trial-specific power conclusion can be drawn.

How should the safety summaries be read statistically?

The adverse-event information is descriptive. The serious-event grouping lists participants at risk and participants affected; the other-adverse-event grouping does the same. These summaries do not provide a comparative safety estimate because no control group is present. The listed serious-event terms have percentages, but the record does not give the event-level data needed to understand recurrence, timing, severity detail, or overlap between terms. General statistical interpretation therefore calls for treating these as reported counts and percentages, not as a causal comparison or a complete description of risk.

Finally, different malignancies were assessed using different methods, including imaging, blood testing, and tumor markers. In general, heterogeneous measurement procedures can complicate interpretation of a combined endpoint if the meaning or timing of assessment differs by disease. The registry describes disease-specific procedures but does not report a statistical method for harmonizing them or analyzing the response separately by diagnosis. That absence limits what can be inferred about the consistency of response measurement across the study population.

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("ODD Regimen")
n      <- c(12)
events <- c(2)
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  ODD Regimen  12  2  16.7  2.1  48.4  4.7  44.8  5.0  45.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy. It lists 3 outcome measures and 0 posted analyses, but it does not specify whether any adjustment for multiple endpoints, disease subgroups, or response categories was planned. Without an analysis plan, it is not possible to determine which outcomes were designated for formal testing beyond the registered primary endpoint or how multiple statistical questions would have been handled.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not say how participants with missing assessments, incomplete follow-up, or unevaluable response status were treated in the primary analysis. It does not state whether the analysis was intended to include all enrolled participants, only those who started treatment, or another defined group. These details matter because the denominator and handling of missing outcome data can affect an endpoint based on participant counts.

As a general statistical point, excluding participants with unobserved outcomes can bias an estimate if the likelihood of missingness is related to response, disease status, or adverse effects. Alternative approaches rely on assumptions that should be stated and assessed. No missing-data assumptions or sensitivity analyses are described in the registry record, so none can be attributed to this trial.

The record’s disease-specific response assessment procedures introduce another interpretive issue. It does not report a plan for pooling response classifications across diagnoses or for subgroup analyses by malignancy type. Nor does it report how the endpoint was handled for participants whose disease assessment used different combinations of imaging, laboratory, or clinical measures. These omissions do not establish that the study lacked such procedures; they mean they are not reported in 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: dehydration (15.4%), pneumonia (7.7%), acute renal failure (7.7%), mucositis (7.7%), elevated alk phos (7.7%).

The ODD group’s serious-adverse-event summary lists 13 participants at risk and 9 affected. The other-adverse-event summary lists 13 at risk and 13 affected. These figures describe the registry’s participant-level group summaries; they do not indicate how many total event episodes occurred. The record does not clarify whether a person with several events is counted once or whether the summaries use a different event-level convention.

The listed serious-event terms are dehydration (15.4%), pneumonia (7.7%), acute renal failure (7.7%), mucositis (7.7%), elevated Alk Phos (7.7%), and elevated AST (7.7%). These are percentages attached to terms in the registry record. The record does not provide the underlying event-level details, timing, duration, or information about overlap between terms. It also does not report a control group, so these figures cannot be used to compare safety with another regimen.

As a general statistical point, serious-event summaries and all-event summaries answer different descriptive questions. They should not be combined or treated as interchangeable. The posted figures are limited to the categories and details the registry reports, and do not by themselves establish causality.

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

The registry record documents a Phase II pilot study of ODD in people described as having refractory lymphoid malignancies. It gives a treatment schedule, outlines disease-specific assessment procedures, and defines tumor response at 16 weeks. It also reports participant counts for serious and other adverse-event groupings, along with selected serious-event terms and percentages. These registry entries describe the trial’s registered design and the safety information recorded in the registry.

The record does not report the primary tumor-response result. It therefore cannot establish from this information how many participants met the response definition, how often each response category occurred, or how precise an estimated response rate would be. Nor does it report an inferential analysis of that endpoint. Absence of a result in this registry record should not be turned into a claim that no response occurred; the result is simply not reported in the registry record.

The design also cannot establish a comparative effect. With a single group and no randomized comparator, the study does not provide a direct contrast against another treatment. General statistical reasoning cautions against interpreting an uncontrolled outcome as proof that the intervention caused that outcome. The registry’s terminated status does not explain why the study ended, and it should not be treated as an outcome finding.

The safety figures are descriptive and should be interpreted within their reported categories. They do not provide a complete account of event timing or overlap and do not support comparative safety conclusions. The record also does not report how missing or unevaluable primary assessments were handled, or which analysis population was used.

In short, the record supplies a defined response endpoint and useful design and safety context, but not the primary efficacy result or a comparative analysis. Conclusions should remain limited to those recorded details. The absence of a posted analysis makes it especially important not to infer an unreported response count, statistical significance, or treatment effect.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between defining an outcome and reporting an outcome. The registry gives a detailed tumor-response definition and a specified assessment time of 16 weeks, including how complete response, partial response, and stable disease lasting more than 2 months are classified. Yet the registry record does not report the observed primary response count or an analysis. Readers can understand what the study intended to measure, but cannot assess the primary result from this record.

It also shows why design determines the reach of an inference. A single-group study can provide descriptive information about participants receiving a regimen, but it cannot create a randomized treatment contrast. The absence of a control arm is particularly important when interpreting an efficacy question: a response observed during treatment is not, on its own, a comparative estimate of what the regimen changed relative to another option.

The trial brings together malignancies with different assessment procedures. Leukemia, lymphoma, and multiple myeloma are described as requiring different kinds of monitoring, which makes endpoint consistency and disease-specific reporting important. The registry does not provide subgroup counts or a method for comparing response across the diagnoses. That omission limits evaluation of whether a pooled endpoint represents similar measurements across the enrolled group.

Finally, this record is a reminder that statistical planning material and trial results serve different purposes. Planning illustrations based on a two-arm setup are not observed results, do not establish the original design rationale, and are not observed power. Clear reporting of the primary result, analysis population, missing-data handling, and statistical plan would be needed for a fuller evaluation of the study’s evidence.

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.

Several limitations specific to this trial affect interpretation. The registry records a single-group design with no masking and no allocation to a comparator. There is no concurrent control for separating outcomes during ODD treatment from the course of disease or other influences. The registry record does not report the reason the study was terminated.

The primary endpoint is defined, but its observed result is not reported. The record therefore lacks the primary response count, any category-specific breakdown, and an estimate of uncertainty. Although the registry lists 3 outcome measures, it reports 0 analyses. A detailed statistical plan, trial-specific sample-size justification, interim analysis plan, and multiplicity approach are not reported in the registry record.

The eligibility description covers a broad range of refractory lymphoid malignancies and allows unlimited prior regimens. The conditions list is narrower than the set of malignancies named in the eligibility summary. The record does not report the number enrolled in each disease category, prior treatment distributions, or baseline characteristics that would clarify the composition of the enrolled group. Disease-specific response assessment methods also differ, and a pooling or harmonization approach is not described.

The registry record does not specify the analysis population or explain how missing, incomplete, or unevaluable response assessments were handled. It does not report subgroup analyses or sensitivity analyses. Finally, the safety information is limited to participant counts and selected serious-event terms with percentages; detailed event-level information and overlap between terms are not reported. These limitations restrict both efficacy interpretation and the completeness of safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Oncaspar/Doxil/Decadron in Patients With Refractory Lymphoid Malignancies — NCT00837200.
• Registry record last updated 2017-07-24; status last verified 2017-06.
• Results first posted 2014-08-20.
• 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 registry record describes a terminated Phase II pilot study of Oncaspar, Doxil, and Decadron in refractory lymphoid malignancies. The design is single group, with no masking and no comparator. The record lists enrollment of 13 and identifies tumor response at 16 weeks as the primary endpoint. Treatment was scheduled in 28-day cycles, with disease assessment procedures varying by malignancy type.

The response criteria include complete response, partial response, and stable disease lasting more than 2 months. The record does not report the observed primary response result, a statistical analysis, or methods for missing data, multiplicity, and analysis populations. Safety summaries list serious and other adverse-event counts and selected serious-event terms with percentages. The record does not explain the termination or provide a trial-specific statistical plan.