Methotrexate, Vincristine, Pegylated L-Asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Methotrexate, Vincristine, Pegylated L-Asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage (NCT00905034), a na phase 2 study. The primary outcome is Complete Response (CR) Rate.

2. Clinical Question

3. Trial Design

This was a phase II study of methotrexate, vincristine, pegylated L-asparaginase and dexamethasone for ALL salvage. The registry lists the study as completed, with 37 participants enrolled. The start is recorded as 2009-03 and primary completion as 2015-02. These dates describe the registry record; they do not supply further detail about the timing of individual participants’ treatment or follow-up.

The design is listed as single-group, with allocation not applicable and no masking. A single-group study observes outcomes among participants receiving the study regimen, rather than estimating a contrast against a concurrent control arm. Without a randomized comparator, differences in outcomes cannot be attributed to the regimen by a between-group comparison. The registry record does not describe a separate control group or a blinded assessment process.

The intervention list names methotrexate, vincristine, PEG-L-asparaginase, dexamethasone and rituximab. The arm description calls the regimen MOAD and includes rituximab; the brief summary qualifies its use as applying to some participants. The record does not explain the criteria or timing for rituximab use, nor does it describe dose schedules or modifications. Those details are not reported in the registry record.

The primary outcome is complete-response rate, assessed at 6 cycles, with a cycle defined as 28 days. The outcome population description says 36 participants completed therapy and were evaluable for response, among the 37 enrolled. The registry lists one outcome measure and zero analyses. It does not report the response numerator, rate, uncertainty interval, hypothesis test, or a detailed statistical analysis plan. The record also does not report a sample-size justification for the trial’s design.

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: Of the 37 participants enrolled, 36 participants completed therapy and were evaluable for response.

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 Complete Response (CR) Rate, measured over 6 cycles (cycle = 28 days).

The primary endpoint was the percentage of participants with a complete response (CR), assessed at 6 cycles, where a cycle was 28 days. CR is a binary outcome: each participant is classified as meeting or not meeting the response definition. The registry describes the rate as calculated from the number of participants with CR, but does not post that number or the resulting percentage.

The definition requires normalization of peripheral blood and bone marrow, with 5% or less blasts in a normocellular or hypercellular marrow. It also requires a granulocyte count of 1 x 10^9/L or above, a platelet count of 100 x 10^9/L or above, and complete resolution of all sites of extramedullary disease. Thus, the endpoint combines marrow and blood findings with the status of disease outside the marrow.

In general, a response endpoint provides a standardized way to describe whether participants meet prespecified disease-status criteria at an assessment time. A binary response rate is easy to interpret as a proportion of a defined population, but it does not by itself describe the duration of response, later disease status, or comparative benefit. Those are distinct questions and require corresponding outcomes and analyses. The registry record does not report those additional results.

The endpoint population is described as the 36 participants who completed therapy and were evaluable for response, rather than all 37 enrolled participants. The record does not report the CR result for either population or explain the status of the remaining participant in relation to the response assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study and lists complete-response rate as its primary outcome. The primary outcome information contains a definition and assessment time, but no observed response count, estimated rate, confidence interval, or statistical test. The record lists zero analyses. Statistical concepts can clarify what such results would ordinarily mean, but they cannot substitute for the missing result.

What does a response rate estimate?

In general, a response rate is a proportion: the number of participants meeting the response definition divided by the participants included in the specified analysis population. Interpreting a proportion requires knowing both the numerator and denominator, along with the rules for classifying participants whose response status is unknown. The registry identifies 36 participants as having completed therapy and being evaluable for response, but does not post how many achieved CR. It also does not describe a separate analysis using all enrolled participants or a rule for missing outcomes.

The endpoint is binary because each participant either satisfies the listed CR criteria or does not. That classification depends on the specified marrow, blood and extramedullary-disease requirements. As a result, the response estimate would describe the frequency of meeting the full definition at the endpoint assessment, not a continuous change in a laboratory measure or an average treatment effect.

What would uncertainty measures convey?

In general, a confidence interval accompanies an estimate to express its statistical precision under a chosen method and assumptions. It is not a guarantee about the true value, nor does it resolve possible bias from selection, missing outcomes or measurement. A narrower interval generally indicates greater precision than a wider interval, while the estimate itself describes the observed data. The registry record does not report a confidence interval for the primary response outcome, so neither the estimated response nor its precision can be reviewed.

In general, a p-value from a hypothesis test describes how compatible the observed data are with a specified null hypothesis under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A test requires a stated comparison or null value and a defined method. The registry record does not report a primary-outcome test, a null value, or a p-value. No test result should be inferred from the phase designation or the fact that the trial enrolled participants.

Why does the design affect interpretation?

In general, a randomized comparison helps make groups comparable on average at baseline, supporting interpretation of a difference in outcomes as an effect of the assigned strategies, subject to remaining limitations. This study is registered as single-group, with allocation not applicable. The record therefore gives no randomized contrast. A single-group response rate can describe the enrolled group under the study regimen, but cannot by itself distinguish regimen effects from other influences on the observed outcome.

The intervention description includes rituximab for some participants, while the record does not explain its use. This means the listed regimen was not described as identical in every respect for every participant. The available record does not provide subgroup definitions or analyses that would permit separate interpretation by rituximab use. No such comparison should be assumed.

What can be said about planning calculations?

The registry includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It says that calculations for time-to-event outcomes use total events, while other calculations use participants per arm. These are described as planning illustrations, not as the trial’s own design justification. The actual study is registered as a single-group trial, so the two-arm assumptions do not describe its registered allocation.

The registry does not report specific calculated participant counts for the planning illustration, and it does not provide the observed CR effect needed to interpret an illustration based on that effect. No sample-size justification for the trial is reported in the registry record. Planning calculations are not observed power: power is a design quantity under assumptions, not a retrospective measure of whether a study’s observed result is convincing. In this record, there is no posted response estimate to support a result-specific assessment.

In general, over-dispersion matters when observed variability is greater than a statistical model assumes; ignoring it can make uncertainty appear too small. That concept is not directly applicable to interpreting a posted estimate: the primary endpoint is binary, and the registry does not provide a fitted model, variance estimate, or analysis details. The record does not say that an over-dispersion adjustment was used.

Which analysis choices are unknown?

The registry does not report whether the response estimate was adjusted for participant characteristics, how the analysis population was defined beyond the evaluable-population description, how missing response assessments were handled, or whether any interim analyses were planned or performed. It also does not report a statistical analysis plan. Without those details and without the actual endpoint result, the analysis cannot be independently reconstructed from the registry 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("MOAD")
n      <- c(36)
events <- c(10)
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  MOAD  36  10  27.8  14.2  45.2  15.8  44.0  15.9  44.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the CR rate, and zero analyses. It does not report whether the study had additional prespecified outcomes outside the listed outcome information, or whether multiple hypotheses, time points or subgroup comparisons were assessed. A multiplicity adjustment is therefore not described in the registry record. In general, when many statistical tests are conducted, the chance of at least one apparently unusual result can increase; methods to address that depend on the planned family of tests. No particular multiplicity approach can be attributed to this study.

The primary outcome description identifies 36 participants as having completed therapy and being evaluable for response, among 37 enrolled. The registry does not give a CR count or rate, explain why the populations differ, or say how participants without evaluable response data were treated. It does not report whether missing outcomes were excluded, imputed, or assigned a response status under a prespecified rule. These details are important because the estimated rate depends on both the denominator and the missing-data approach.

The analysis population is not otherwise described in detail. The record does not establish whether the primary analysis followed an intention-to-treat approach, a per-protocol approach, or another definition. It also does not report analysis-specific participant counts beyond the statement about therapy completion and response evaluability. Therefore, the response denominator and analysis population cannot be independently verified from the posted primary outcome information.

In general, missingness can affect interpretation when the probability of an unavailable outcome is related to participants’ response status or other characteristics. The registry record does not provide enough information to assess that possibility or to judge the direction of any effect. No missing-data method should be inferred.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (37.8%), pneumonia (24.3%), neutropenic fever (18.9%), hypotension (10.8%), mucositis (10.8%).

The registry’s adverse-event information lists 37 participants at risk in the MOAD group. Its serious-event group fields list 33 participants affected, while the other adverse-event group fields list 37 affected. The record also lists serious adverse-event terms with percentages: Death, 37.8%; Pneumonia, 24.3%; Neutropenic Fever, 18.9%; Hypotension, 10.8%; Mucositis, 10.8%; and Weakness, 8.1%.

These figures describe adverse-event reporting in the registry; they do not establish that an event was caused by the regimen. The entry for Death is a listed serious-event term with a percentage. The record does not provide a deaths count in the field for deaths, so that count is not reported in the registry record. The percentages should not be treated as a comparison with another treatment because no control group is described.

In general, adverse-event summaries depend on the event definitions, observation period, collection rules and denominator used. The registry entry does not give further detail on those aspects, nor does it report event timing, severity grades beyond the serious-event categorization, or participant-level overlap among terms. One participant may have experienced more than one event; the posted term percentages do not establish whether categories are mutually exclusive. These limitations constrain what can be concluded from the safety figures.

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

The registry record establishes that a phase II, single-group study of the MOAD regimen was conducted in a salvage setting and that complete-response rate was its registered primary outcome. It defines CR using blood, bone-marrow and extramedullary-disease criteria and identifies the assessment at 6 cycles, with a cycle defined as 28 days. It also reports that 36 participants completed therapy and were evaluable for response out of 37 enrolled.

However, the record does not report how many participants achieved CR or the resulting rate. It also does not report an uncertainty interval or a statistical test. As a result, the primary outcome’s magnitude and precision cannot be described from the registry entry. The absence of a posted result should not be interpreted as a null result, a favorable result, or evidence that no responses occurred.

Even a fully reported response rate from this design would describe the observed response frequency in the study population, not a randomized treatment effect. Since the study has no separate comparison group, it cannot directly estimate how outcomes would compare with another strategy. Nor does a response endpoint alone indicate how long responses lasted or how outcomes changed after the assessment point.

The safety entries provide counts of participants at risk and affected, together with percentages for listed serious-event terms. They do not establish causation, and the registry does not provide a deaths count in its deaths field. Interpretation is limited by the absence of additional information on event definitions, timing and overlap.

Accordingly, the registry supports a careful description of study design, endpoint criteria, response-evaluable population and posted safety entries. It does not support a numerical conclusion about the primary response outcome or a comparative conclusion about treatment effects. Those conclusions require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why a registered outcome definition and an observed outcome result are both necessary for statistical interpretation. The CR criteria are described in detail, and the assessment time and response-evaluable population are identified. Yet the response count and rate are not posted. Without the numerator, a reader cannot quantify the endpoint; without an uncertainty measure, precision cannot be assessed.

The difference between enrollment and response evaluability also highlights the importance of analysis populations. The registry reports 37 enrolled participants and says that 36 completed therapy and were evaluable for response. It does not explain the remaining participant’s outcome status or the analysis rule. A clear account of how participants enter the denominator is essential to interpreting a proportion.

The single-group design is another central statistical feature. Such a design can describe outcomes in participants receiving a regimen, but it does not provide a randomized concurrent comparison. This limits causal interpretation even when an outcome estimate is available. The registry’s planning assumptions refer to equal allocation between two arms, whereas the registered trial design is single-group. That planning illustration is not evidence that the study itself had two arms or that it was designed around a particular sample-size justification.

Finally, the safety entries demonstrate why event percentages need their reporting context. The registry lists affected participants and serious-event terms, but does not provide event timing, detailed collection rules or a death count in the deaths field. Clear denominators and event definitions help readers distinguish reported frequencies from causal conclusions.

Statistically, the record is most informative about the planned endpoint and study structure, rather than the primary result. Keeping that distinction explicit prevents the design description from being mistaken for evidence about the size or certainty of an outcome.

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 endpoint is that the registry record does not report the CR count or rate. It also does not provide a confidence interval, p-value or other uncertainty estimate. Consequently, the primary outcome’s observed magnitude and precision are unavailable.

The outcome population is described as 36 participants who completed therapy and were evaluable for response, compared with 37 enrolled. The reason for this difference, the remaining participant’s response status and the missing-outcome handling are not reported in the registry record. The analysis population and denominator therefore cannot be fully assessed.

The single-group design has no concurrent comparator, and the record lists allocation as not applicable. The study can be described as a cohort receiving the regimen, but a comparative treatment effect cannot be estimated from the registered design. The record also says rituximab was used in some participants without describing selection criteria or reporting a subgroup analysis, limiting interpretation of regimen exposure.

The registry lists serious adverse-event terms and percentages, but additional details about event definitions, timing, duration, severity grading and overlap are not reported. A death count is not listed in the deaths field. These omissions limit safety interpretation and preclude treating the event percentages as evidence of causation.

The statistical analysis plan, any interim analyses, adjustment methods and detailed missing-data procedures are not reported in the registry record. Although planning assumptions are described, the record does not provide a trial-specific sample-size justification or participant counts from those planning illustrations. These gaps mean that the registered results cannot be independently reconstructed or evaluated against a complete prespecified analysis plan.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Methotrexate, Vincristine, Pegylated L-Asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage — NCT00905034.
• Registry record last updated 2015-06-29; status last verified 2015-06.
• Results first posted 2015-06-29.
• 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

NCT00905034 is a completed phase II, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 37 participants and evaluated the MOAD regimen for ALL salvage. The regimen included methotrexate, vincristine, pegylated L-asparaginase and dexamethasone; the summary says rituximab was used in some participants.

The primary outcome was CR rate at 6 cycles, with a cycle defined as 28 days. The registry defines CR and states that 36 participants completed therapy and were evaluable for response. It does not report the CR count or rate, and lists zero analyses. No comparator group is described.

Adverse-event information lists 37 participants at risk, 33 affected in the serious-event group, and serious-event terms with percentages. The registry does not provide a deaths count in the deaths field. The available record therefore describes the design, endpoint definition and selected safety entries, but does not report the primary response result or enough analysis detail to assess its precision.