A Study in Adults With Untreated Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Adults With Untreated Acute Lymphoblastic Leukemia (NCT00136435), a na phase 2 study. The primary outcome is Asparaginase Completion Rate.

2. Clinical Question

3. Trial Design

This was a phase II, multicenter study sponsored by Dana-Farber Cancer Institute. The registry describes a single-group model, allocation as not applicable, and no masking. Enrollment was 100. The record lists the study as completed, with a start of 2002-06 and primary completion in 2008-11. These design features describe a study of outcomes under one treatment approach; they do not provide a randomized comparison with a control group.

The treatment approach was based on the Dana-Farber Cancer Institute pediatric consortium protocol and tested pharmacokinetically individualized doses of L-asparaginase in adults with untreated ALL. Listed interventions included prednisone, doxorubicin, vincristine, methotrexate, asparaginase, dexamethasone, cranial radiation, and leucovorin. The registry record does not specify the detailed dosing algorithm, how dose adjustments were implemented, or the timing and frequency of pharmacokinetic measurements.

The primary endpoint was an asparaginase completion rate. The analysis dataset is described as all patients who initiated asparaginase consolidation therapy, while completion is defined among patients who achieved complete remission after induction and completed all 30 intensification doses. The record does not state how many participants reached each treatment stage or how the analysis handled patients who did not achieve remission or did not initiate consolidation.

Secondary outcomes listed include 4-year disease-free survival, 4-year overall survival, 4-year event-free survival, post-induction nadir serum asparaginase activity level, and the number of participants with asparaginase-related toxicity. The record lists six outcome measures but names five secondary outcomes. It reports no analyses for these outcomes. The protocol, sample-size justification, interim analysis procedures, and detailed statistical 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all patients who initiated asparaginase consolidation therapy.

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: The analysis dataset is comprised of all enrolled patients.

6. Primary Endpoint

The registry lists the primary outcome as Asparaginase Completion Rate, measured over Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first..

The primary endpoint is the asparaginase completion rate, expressed as a percentage. It measures the proportion of relevant patients who completed all 30 doses of asparaginase during intensification after achieving complete remission following induction. The registry describes the analysis dataset as all patients who initiated asparaginase consolidation therapy. The endpoint was assessed at the end of the 30-week post-induction treatment period or when a participant came off treatment, whichever occurred first.

Complete remission is defined in the record by several criteria: peripheral blood without lymphoblasts, bone marrow with <5% lymphoblasts, an antigen-presenting cell (APC) > 1000/mm3, platelets > 100,000/mm3, and no evidence of extramedullary leukemia. These criteria define which remission status is relevant to the completion measure; they are not themselves the primary endpoint.

A completion percentage is useful for describing whether a treatment schedule can be delivered through its planned course in the population specified for analysis. It focuses on treatment delivery, not on a comparison of treatment effects between groups. In general, the percentage depends on a clear numerator and denominator. The registry gives a population description and a completion definition but does not report the observed count, the analyzed denominator, or the resulting percentage. It also labels the dispersion as an 80% confidence interval without reporting the interval limits. Thus, the endpoint's intended meaning is clear, but its estimated value and precision cannot be read from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary event at the participant level: completion of all 30 asparaginase doses, or failure to meet that completion definition. A binary outcome can be summarized as the percentage of participants with the event. In this study, the relevant population is described as patients who initiated asparaginase consolidation therapy, while the completion definition further refers to patients who achieved complete remission after induction. The record does not report the number of participants in the analyzed population or the event count, so the completion percentage cannot be reconstructed.

What does a confidence interval express?

A confidence interval describes uncertainty around an estimated quantity. For a percentage, the interval reflects how imprecisely the underlying event frequency is estimated from the observed participants, under the statistical method used. A narrower interval generally indicates greater precision; a wider interval indicates less precision. The registry labels the primary outcome's dispersion as an 80% confidence interval, but it does not report either endpoint of that interval or identify the method used to calculate it. The confidence level alone cannot recover the estimate or its precision.

A confidence interval is not a guarantee that a particular range contains the true value, nor does it substitute for the observed percentage. Interpretation requires the estimate, the interval limits, and the analysis population. Those numerical results are not reported in the registry record. The record also does not report a hypothesis test or an estimated comparison for this primary endpoint.

Why does the single-group design matter?

In a single-group design, the observed outcome describes participants receiving the study's treatment approach. Without a concurrent comparison group, changes or outcomes cannot be directly contrasted with outcomes under another strategy within the trial. This matters even when an endpoint is measured objectively: a completion proportion is still a description of the group rather than a randomized estimate of the difference between treatment options. Allocation is recorded as not applicable, and the record identifies only one arm.

Pharmacokinetically individualized dosing is the approach under study, but a single-group design does not by itself separate the contribution of that dosing approach from other parts of the regimen, participant characteristics, or the course of the disease. The listed interventions form a broader treatment program. No comparative or adjusted analysis is reported in the registry record.

What can be learned from an event percentage?

In general, an event percentage is calculated from the number of participants meeting the event definition relative to the number of participants in the specified analysis population. The numerator and denominator must refer to compatible populations and time windows. Here, completion is assessed through the end of the 30-week post-induction treatment period or when a participant comes off treatment, whichever occurs first. The record does not state the observed numerator or denominator, so readers cannot evaluate the percentage, check its calculation, or determine how many participants stopped treatment before the assessment point.

For time-to-event outcomes such as overall survival, disease-free survival, or event-free survival, methods generally account for both event timing and follow-up. Participants may have different follow-up durations, and some may not have experienced the event by the end of observation. The registry lists 4-year outcomes but supplies no estimates, event counts, censoring information, or analysis method. No time-to-event result can therefore be interpreted from the record. This is a general description of such methods, not a claim about what was done in this study.

How should planning calculations be distinguished from trial results?

Planning calculations address hypothetical design questions, such as how many participants might be needed to detect a specified effect under stated assumptions. They are not observed outcomes and should not be read as evidence that a study had a particular probability of finding a result. In general, calculations depend on choices such as significance level, allocation, and the effect targeted for detection. The record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also says the effect to detect is a stated fraction of the observed effect. These are assumptions for a planning illustration, not the single-group trial's design. The registry record does not report the trial's own sample-size justification, and there are no reported primary endpoint estimates from which to assess the observed completion result.

Likewise, a recalculation from summary statistics, if available, would be an unadjusted calculation and would not replace the sponsor's analysis when the two differ. No primary analysis result or discrepancy is reported in the registry record. It is therefore not possible to assess agreement between a sponsor analysis and a recalculation for this endpoint.

Why does over-dispersion matter in other outcome types?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a method assumes less variability than the data contain, estimated uncertainty may be too small and intervals may appear more precise than warranted. This is relevant to some count or rate outcomes, but the primary endpoint is a percentage. The registry does not report a model, an over-dispersion assessment, or enough primary outcome data to determine whether this issue arose in the study.

Across all methods, definitions and analysis populations are central. The registry gives a remission definition, a completion definition, and a description of the primary analysis dataset. It does not state how missing observations, treatment discontinuation, or participants who did not reach consolidation were handled. Without those details and the actual outcome counts, the endpoint's estimate and statistical precision remain unavailable.

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("Induction, CNS, and Intensification With Pharmacok")
n      <- c(57)
events <- c(36)
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  Induction, CNS, and Intensification With Pharmacok  57  36  63.2  49.3  75.6  50.2  74.5  50.1  74.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: asparaginase completion as the primary measure, along with 4-year disease-free survival, 4-year overall survival, 4-year event-free survival, post-induction nadir serum asparaginase activity level, and the number of participants with asparaginase-related toxicity. It lists six outcome measures overall but names five secondary outcomes. The record reports no analyses for these outcomes and does not give results for the primary or secondary measures.

When a study examines multiple outcomes, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently notable finding. Statistical plans may identify a primary outcome, specify which analyses are confirmatory, and describe any adjustment or hierarchy for other outcomes. The registry record identifies a primary endpoint but does not report a multiplicity strategy, a testing hierarchy, or a statistical analysis plan. It would therefore be inappropriate to infer that any unreported secondary outcome was tested or that a particular adjustment was used.

Missing-data handling is also not reported in the registry record. The endpoint depends on treatment progression and completion, and the analysis population is described as patients who initiated asparaginase consolidation. The record does not state how participants who stopped treatment, lacked endpoint information, did not achieve complete remission, or did not initiate consolidation were treated in the analysis. It also does not report how many participants had missing data. These omissions prevent assessment of whether missingness could influence the completion percentage.

The registry does not report an interim analysis plan, sample-size justification, or detailed statistical analysis plan. These gaps do not establish that such procedures were absent from the full study documentation; they mean that they are not reported in the registry record. Consequently, neither control of multiplicity nor robustness to missing data can be evaluated from this record.

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

Serious events with the highest arm-level rate: anemia (95.9%), neutrophil count decreased (95.9%), platelet count decreased (92.9%), alanine aminotransferase increased (91.8%), aspartate aminotransferase increased (90.8%).

For the listed study group, the registry reports 98 participants at risk and 98 affected by serious adverse events. It reports 98 at risk and 0 affected in the other adverse-event grouping, and 40 deaths. These counts should be read as registry safety summaries for the group, not as a comparison between treatment arms. There is only one listed arm, and the record does not identify a control group.

The serious adverse-event terms with the highest listed percentages are anemia and neutrophil count decreased, each reported as 95.9%; platelet count decreased at 92.9%; alanine aminotransferase increased at 91.8%; aspartate aminotransferase increased at 90.8%; and nausea at 84.7%. The registry does not give event counts for each term alongside these percentages, nor does it report timing, duration, severity grades, or attribution. Individual participants may experience more than one adverse event as a general feature of safety reporting, so percentages for separate terms should not be added to make a total.

The death count is reported without an explanation of cause or treatment attribution. The registry record does not establish that the deaths were caused by the study treatment, nor does it provide a comparison that could estimate excess risk. The safety figures describe what the record reports; they do not alone determine causal relationships.

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

The registry record supports a description of a phase II, single-group study that assessed pharmacokinetically individualized L-asparaginase dosing within a broader protocol for adults with untreated ALL. Its primary endpoint was designed to measure the percentage of eligible patients who completed all 30 asparaginase doses during intensification. The endpoint definition, assessment period, remission criteria, and analysis-population description are available.

However, the record does not report the observed primary completion percentage, its numerator or denominator, or the stated 80% confidence interval. The enrollment figure of 100 is not a substitute for the analysis population or endpoint result. The record also does not report analyses of the named secondary outcomes. As a result, the registry alone cannot establish the completion rate, survival estimates, serum activity findings, or the result for asparaginase-related toxicity.

The reported safety summaries indicate that 98 of 98 participants in the listed group were affected by serious adverse events, with the listed percentages for several common serious-event terms. The record also gives 0 affected in its other adverse-event grouping and reports 40 deaths. These values are not comparative treatment effects. The record does not identify the cause or treatment relationship of the deaths, or provide details that would support causal interpretation of individual adverse events.

The single-group design is important to what can be concluded. Even if the primary percentage were available, it would describe the study group and would not, by itself, show what would have happened under a different dosing approach. No concurrent control is described, and the registry does not report comparative analyses. The posted information therefore explains what the trial set out to measure and gives selected safety counts, but it does not permit a complete assessment of efficacy, precision, or comparative safety. These limits concern what is reported in the registry record; they should not be mistaken for proof that a result was absent from other study documentation.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring feasibility and estimating comparative benefit. Its primary endpoint asks whether participants who achieved remission completed the planned asparaginase course. A completion percentage can describe whether a regimen was delivered in the defined population, but it is not equivalent to a comparison of outcomes under alternative regimens. In a single-group study, the interpretation remains descriptive unless a suitable comparison is available from another source and analyzed with appropriate methods.

The record also illustrates why analysis populations need to be explicit. Enrollment was 100, while the primary analysis dataset is described as patients who initiated consolidation. The completion definition refers to participants who achieved complete remission and finished all doses. Those are related but distinct stages. Knowing the number at each stage, how the denominator was chosen, and how participants who did not complete treatment were handled is essential to understanding a feasibility estimate. The registry does not provide those counts or details.

Precision matters alongside the percentage itself. The record labels the primary endpoint's dispersion as an 80% confidence interval, but reports neither its limits nor the underlying estimate. Without both, readers cannot judge how much uncertainty surrounds the feasibility measure. The record also names several secondary outcomes, underscoring the importance of a prespecified analysis plan and clear handling of multiple outcomes. Such a plan is not reported in the registry record.

Finally, the safety summaries show why descriptive adverse-event counts need context. The record gives serious-event counts and percentages but no control group, event attribution, or detailed timing. These figures can describe the observed safety reporting in the study group, but they cannot alone establish causal effects. The trial is statistically informative as an example of how endpoint definitions, analysis populations, design, and reporting jointly determine the conclusions that can be drawn.

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 interpreting the primary outcome is that the registry record does not report its result. The completion percentage, event count, analysis denominator, and 80% confidence interval are absent. Although enrollment was 100, the analysis population is specifically described as patients who initiated asparaginase consolidation. The number who entered that population is not reported, so enrollment cannot be used as the endpoint denominator.

The study has a single-group design, with no separate comparator arm, allocation not applicable, and no masking. These features limit causal and comparative interpretation. The intervention was a multi-component treatment approach, and the record does not report analyses that separate the contribution of individualized L-asparaginase dosing from other treatments or aspects of care.

Important implementation details are not reported in the registry record, including the dose-adjustment algorithm, pharmacokinetic measurement schedule, and detailed statistical methods. The record also does not report the sample-size justification, interim analysis procedures, or a plan for multiplicity. Missing-data rules and the handling of participants who did not reach remission, did not initiate consolidation, or discontinued treatment are likewise not reported.

Several secondary outcomes are named, but results and analyses are not reported. The safety information includes counts, selected event-term percentages, and deaths, but lacks timing, event-level counts for the listed terms, severity grading, attribution, and a comparator. Thus, these safety summaries do not support a causal assessment. These limitations concern the information reported in the registry record and do not establish what may or may not appear in other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Adults With Untreated Acute Lymphoblastic Leukemia — NCT00136435.
• Registry record last updated 2025-10-20; status last verified 2025-10.
• Results first posted 2025-10-20.
• 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

The registry describes NCT00136435 as a completed phase II, multicenter, single-group study sponsored by Dana-Farber Cancer Institute. It enrolled 100 adults with untreated acute lymphoblastic leukemia and tested pharmacokinetically individualized L-asparaginase dosing within a broader protocol. The primary endpoint was the percentage completing all 30 doses of asparaginase during intensification among the population described as initiating consolidation.

The record defines the remission criteria and assessment period, and lists secondary outcomes for survival, serum asparaginase activity, and toxicity. It reports selected serious adverse-event counts and percentages and 40 deaths. It does not report the primary endpoint estimate or its 80% confidence interval, secondary outcome analyses, detailed statistical methods, or missing-data handling. With no separate comparator group, the design supports description of the study group rather than a randomized treatment comparison.