Treatment of Older Adults With Acute Lymphoblastic Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Older Adults With Acute Lymphoblastic Leukemia (NCT00973752), a na phase 2 study. The primary outcome is Overall Survival at One Year.

2. Clinical Question

The clinical question is about outcomes following a treatment approach in older adults with ALL, not about estimating a randomized treatment contrast. The registry describes the regimen as a combination of drugs used in ALL treatment, with clofarabine and PEG-asparaginase added, and with imatinib for the subgroup with the Philadelphia chromosome. The reported study structure has one treatment arm. That structure can describe what occurred among participants treated in the study, but it does not by itself separate treatment effects from other explanations for the observed outcomes.

3. Trial Design

The registry lists this study as phase 2, with a single-group model and one experimental arm. The arm description says all patients were treated on the same arm. Allocation is recorded as NA and masking as none. These entries describe a study without a registered randomized allocation or masking procedure; the registry does not identify a control arm for a direct comparison.

The planned enrollment is recorded as 30. The study status is completed. The recorded start is 2009-08, and primary completion is recorded as 2014-12. Massachusetts General Hospital is listed as the sponsor. Acute lymphoblastic leukemia is the registered condition. The record does not report additional sites, eligibility thresholds, or participant characteristics in the registry record for this analysis.

The brief summary describes treatment with a multi-drug regimen, including prednisone, vincristine, cytarabine, doxorubicin, 6 mercaptopurine, and methotrexate, in combination with PEG-asparaginase and clofarabine. The registry intervention list names prednisone, vincristine, doxorubicin, PEG-asparaginase, cytarabine, methotrexate, imatinib, and clofarabine. The difference in those lists should be kept visible rather than resolved by assumption: the summary names 6 mercaptopurine, while it is not included in the intervention list. The brief summary says imatinib is for participants with the Philadelphia chromosome.

The primary outcome is Overall Survival at One Year, defined as the number of participants alive one year after baseline. One outcome measure is registered, and no analyses are listed. The record does not describe a statistical analysis plan, a separate comparator, or a planned interim analysis. Those details 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

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 Overall Survival at One Year, measured over 1 years.

The primary endpoint is the number of participants alive one year after baseline. It is a count outcome, expressed in participants, over the stated timeframe of 1 years. Overall survival is a time-to-event concept: it concerns whether a participant is alive at a specified time, with death as the event. In this registry entry, however, the stated measure is a count alive at the one-year point rather than a reported survival curve or a hazard estimate.

As a general statistical explanation, survival outcomes are often used because they describe how long participants remain alive over follow-up, while a fixed-time summary focuses on status at a particular follow-up point. A fixed-time count is straightforward to interpret only alongside the number assessed and the handling of participants whose status is unknown. The registry record does not report the observed number alive at one year, the number whose status was available at that point, or how missing status was handled.

Consequently, the endpoint definition is available but its observed result is not. The count cannot be reconstructed from the enrollment entry or from the adverse-event figures. The one-year outcome also does not, on its own, establish how the regimen compares with another treatment, because the registered design has a single group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study observes outcomes among participants assigned to or treated within one study arm. Its descriptive results can characterize that group during the study. A treatment comparison requires a second group or another credible source of comparison. Here, the registry lists one experimental arm and says all patients were treated on the same arm. Allocation is NA. As a general statistical principle, without a comparison group, an observed outcome cannot separate the effect of treatment from the natural course of disease, differences in participant characteristics, or other influences on outcomes.

This design does not make descriptive outcomes uninformative. It does limit the questions those outcomes can answer. A one-year survival count would describe the study participants’ status at that time, if reported and if follow-up status were sufficiently clear. It would not by itself demonstrate what would have happened to those same participants under a different regimen. The record does not report a comparative effect estimate.

How should a fixed-time survival endpoint be read?

The registered primary endpoint is the number of participants alive one year after baseline. It is a count, rather than a reported survival probability or a time-to-event model estimate. General statistical interpretation of a fixed-time survival result depends on knowing both the count and the number of participants with outcome status assessed at that point. The registry does not report the one-year count or the status of participants whose follow-up may not have reached or documented that point.

A confidence interval, when reported, expresses uncertainty around an estimated quantity under the assumptions of the analysis. It is not a guarantee that the true quantity lies within the interval, and it does not resolve design limitations such as the lack of a control group. No confidence interval for the primary outcome is reported in the registry record. No standard error, survival curve, or other precision measure for that outcome is reported either.

What do the planning assumptions mean?

The record includes sample-size assumptions for a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, with time-to-event illustrations expressed as total events and other illustrations expressed as participants per arm. These are planning conventions, not results from this single-group study. The record does not provide a trial-specific sample-size justification or a registered two-arm comparison to which those assumptions could be directly applied.

As a general explanation, a planning calculation asks how much information a proposed study might need to detect a specified effect under stated assumptions. It does not say that an effect was observed in this trial, and it is not observed power. A planning illustration based on an observed effect can also depend on the uncertainty and context of that effect. No sample-size illustration should be read as evidence that the present study had a particular probability of detecting a treatment effect.

Why do analysis details matter?

Analysis methods specify how outcomes are calculated, which participants are included, how missing observations are treated, and how uncertainty is quantified. They also clarify whether estimates are adjusted for other variables or whether multiple outcomes or comparisons are considered. The registry lists one outcome measure and zero analyses. It does not report the analysis population, an adjustment method, a statistical test, or a method for handling missing outcome data. These omissions prevent independent assessment of how a primary-outcome estimate would have been produced.

As a general statistical principle, over-dispersion matters when count data vary more than a model’s assumed distribution allows. A model that ignores that extra variability can understate uncertainty. The registered primary outcome is a count, but the record does not report a count model or any dispersion parameter. There is no basis to claim that over-dispersion was assessed or to infer that a particular count-model method was used.

Multiplicity refers to the increased chance of false-positive findings when many hypotheses are tested. A prespecified primary outcome and analysis can help distinguish confirmatory questions from exploratory ones. The registry identifies one primary outcome but no analyses. It does not report whether other outcomes were tested or whether any multiplicity procedure was planned. No conclusion about multiplicity adjustment can be drawn from the record.

For the adverse-event counts, interpretation also depends on the event definitions and reporting rules. The record gives affected and at-risk counts and lists leading serious terms with percentages. It does not specify in the registry record whether events were counted once per participant, whether recurrent events were included, or how overlapping terms were handled. Accordingly, term percentages describe the listed categories and should not be combined into a total or interpreted as independent risks.

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("Experimental")
n      <- c(30)
events <- c(19)
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  Experimental  30  19  63.3  43.9  80.1  45.5  78.1  45.4  78.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, Overall Survival at One Year, and zero analyses. It does not report an analysis plan, statistical tests, confidence intervals, covariate adjustments, or a strategy for controlling multiplicity. A single registered primary outcome can make the main question easier to identify, but the absence of listed analyses means the methods used to estimate or test that outcome cannot be evaluated from this record.

The analysis population is not specified in the available record. The record does not say whether all enrolled participants were included in the primary outcome analysis, whether eligibility or treatment exposure determined inclusion, or whether any participants were excluded from analysis. It also does not report the number with one-year status available.

Missing-data handling is not reported in the registry record. For an endpoint defined by survival status at one year, missing status can affect the interpretation of the count. The record does not describe censoring, follow-up completion, imputation, or any sensitivity analysis. No method should be assumed.

Multiplicity procedures are likewise not reported. Although one primary outcome is registered, the record does not state whether secondary outcomes or exploratory analyses were conducted or how multiple tests, if any, were handled. These gaps do not show that a particular method was or was not used outside the record; they limit what can be assessed from the registry entry.

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: hyperbilirubinemia (33.3%), infection w/ gr. 3/4 neutropenia (23.3%), transaminitis (23.3%), hyperglycemia (23.3%), infection - other (10.0%).

The registry reports 10 participants affected by serious adverse events, with 30 at risk in the experimental group. It separately reports 18 participants affected by other adverse events, also with 30 at risk. These are group-level affected counts. The record does not state whether the same participant could be included in both categories, so the counts should not be added or interpreted as a count of distinct participants.

The listed serious adverse-event terms and percentages are Hyperbilirubinemia, 33.3%; Infection w/ gr. 3/4 neutropenia, 23.3%; Transaminitis, 23.3%; Hyperglycemia, 23.3%; Infection - other, 10.0%; and Allergic Reaction, 10.0%. The record does not report term-specific counts in the registry record, nor does it explain whether one participant could contribute to more than one term. The percentages therefore should not be summed or treated as mutually exclusive categories.

These figures describe reported safety events in the study group. They do not establish how frequently the same events would occur under another treatment or without treatment. The record does not provide a comparator for that purpose, and it does not report exposure-adjusted rates, event timing, or a detailed severity breakdown beyond the terms that refer to grade 3/4 neutropenia.

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

The registry record establishes that this was a completed phase 2 study of a multi-drug regimen in older adults with acute lymphoblastic leukemia. It identifies one-year overall survival as the primary outcome and reports adverse-event affected counts for the experimental group. It does not report the primary-outcome count, so the record cannot support a numerical description of how many participants were alive one year after baseline.

The study’s single-group structure is central to what can be concluded. The record lists no comparator and no random allocation. A descriptive outcome among participants treated on the regimen would not, by itself, establish a causal treatment effect or show how that outcome differs from another treatment. This is a limitation of the comparison the design can make, not a judgment about the clinical value of the regimen.

The adverse-event figures show that serious and other adverse events were recorded among participants in the experimental group. They are not comparative estimates of safety. The term percentages also should not be combined: the record does not state that categories are mutually exclusive, and one participant may have been represented in more than one term.

The record does not report confidence intervals or analysis details for the primary outcome. Therefore, its precision cannot be assessed, and no statistical-significance conclusion can be drawn. The planned enrollment of 30 is not the same as the number with complete one-year follow-up, which is not reported. Nor does enrollment alone establish the amount of information available for the endpoint.

In short, the record describes the trial’s intended population, regimen, design, endpoint definition, and some safety results. It does not report enough primary-outcome or analysis information to quantify one-year survival, compare treatment strategies, or assess the precision of a treatment-effect estimate.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and outcome reporting must be read together. The registry names a specific primary endpoint, Overall Survival at One Year, and defines it as a participant count alive at that follow-up point. Yet the result for that endpoint is not reported. Knowing the endpoint definition does not supply its estimate, and knowing the planned enrollment does not show how many participants had outcome status documented.

The study is listed as single group, with all patients treated on the same arm. This makes the distinction between describing an outcome and estimating a treatment effect especially important. A single-group result could characterize what happened among participants in the study, but it would not provide a randomized comparison. The registry entries therefore do not support a causal contrast with another regimen.

The safety information also illustrates why categories and denominators need careful interpretation. The record reports affected counts and at-risk counts, along with percentages for selected serious adverse-event terms. Without information about overlap among terms, those percentages cannot be added to create a total. Without a comparison group, they also cannot establish relative safety.

Finally, the record lists no analyses and does not report methods for missing outcome data, precision, or multiplicity. These are not merely technical details: they determine how a result is estimated and how much confidence readers can place in it. The trial’s statistical contribution cannot be judged fully from the registry entry without the missing primary-outcome result and analysis details.

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 most direct limitation for interpreting the primary endpoint is that the one-year survival count is not reported in the registry record. The number with outcome status available at that time is also not reported. Consequently, neither the observed result nor its precision can be assessed.

The design is single group, with no registered comparator and allocation listed as NA. This limits causal interpretation and prevents a like-for-like treatment comparison within the record. The absence of a comparator is distinct from the absence of an outcome result: even if the outcome count were available, it would remain a within-group description rather than a randomized contrast.

The registry does not report eligibility details, participant characteristics, follow-up completeness, or how participants with missing one-year status were handled. It also does not report the primary-outcome analysis population, statistical test, confidence interval, or analysis plan. These omissions restrict assessment of selection, missingness, and uncertainty.

There is a difference between the brief summary and intervention list: the summary names 6 mercaptopurine among regimen components, while the intervention list does not include it. The record does not clarify this discrepancy. The safety information also lacks details about whether adverse-event categories overlap, event timing, or exposure-adjusted rates. The serious-event term percentages should therefore be interpreted as listed, not combined into an overall rate.

These limitations describe what cannot be established from the registry record; they do not show that additional information was never collected or analyzed outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Older Adults With Acute Lymphoblastic Leukemia — NCT00973752.
• Registry record last updated 2017-03-30; status last verified 2017-02.
• Results first posted 2017-03-30.
• 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

NCT00973752 is a completed phase 2, single-group study sponsored by Massachusetts General Hospital. It concerns treatment of older adults with acute lymphoblastic leukemia. The record lists planned enrollment of 30, a start of 2009-08, and primary completion of 2014-12.

The study regimen is described as a multi-drug approach involving clofarabine and PEG-asparaginase with other ALL drugs; participants with the Philadelphia chromosome were also to receive imatinib. The primary endpoint is the number of participants alive one year after baseline. The registry does not report that outcome’s observed count or a statistical analysis.

For the experimental group, the record reports 10 participants affected by serious adverse events and 18 affected by other adverse events, with 30 at risk in each category. No randomized comparator is registered, so the record supports description of the study design and reported safety information, but not a comparative treatment-effect estimate.