Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML) (NCT00890929), a na phase 1, phase 2 study. The primary outcome is Compete Remission (CR) Rate.

2. Clinical Question

The study addressed two related questions in previously untreated elderly patients with acute myeloid leukemia. Its phase 1 component aimed to determine the maximum tolerated dose of lenalidomide when given after azacitidine. Its phase 2 component aimed to assess the efficacy of the combination, with complete remission rate designated as the primary outcome over 12 months.

The phase 1 and phase 2 aims are distinct. Dose finding concerns tolerability across dose levels; an efficacy assessment concerns outcomes among participants receiving the regimen. The record does not report the selected maximum tolerated dose or a numerical estimate of the primary remission outcome. It therefore supports describing the study question and structure, but not judging the magnitude or precision of a remission result.

3. Trial Design

This was a phase 1–2 study sponsored by Stanford University. It is listed as completed, with enrollment of 45. The record gives a start date of 2009-04 and a primary completion date of 2011-06. The study concerned previously untreated elderly patients with acute myeloid leukemia and evaluated azacitidine followed by lenalidomide.

The design is recorded as single group, with allocation not applicable and no masking. The arm description says “Dose escalation then dose expansion.” That is consistent with the stated two-part purpose: dose finding in phase 1 and efficacy assessment in phase 2. The registry does not report further details about the dose-escalation rules, the dose-expansion cohort, or how participants moved between the components. Such operational details should not be inferred from the brief description.

With no separate control arm, the study can describe outcomes among participants treated in the study, but it cannot provide a randomized comparison with another treatment or a concurrent control group. Changes over time or outcomes observed in this group cannot, by themselves, distinguish a treatment effect from other explanations. This design is suited to describing experience with the regimen and pursuing the stated dose-finding objective; it has a different comparative interpretation from a randomized trial.

The record names lenalidomide and azacitidine as drug interventions. It identifies one treatment group, “Azacitidine Followed by Lenalidomide,” for the adverse-event information. Masking is listed as none, so the record does not describe a blinded assignment or outcome assessment. The registry does not report additional details about the allocation process beyond the single-group designation, nor does it describe a separate efficacy comparator.

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:

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 Compete Remission (CR) Rate, measured over 12 months.

The primary endpoint is titled “Compete Remission (CR) Rate” in the registry record. Its unit is the percentage of subjects, and its timeframe is 12 months. The description says that CR includes subjects with complete remission but incomplete recovery of blood counts, identified as CRi. It also states that CR was assessed according to European LeukemiaNet guidelines and defines it as the absence of clonal lymphocytes in peripheral blood.

In general, a remission rate is a binary-outcome summary: each participant is classified according to whether the specified remission event occurred, and the rate expresses the proportion meeting that definition. Including CRi means the endpoint is not limited to participants who meet the record’s CR category without incomplete blood-count recovery. That distinction matters because the endpoint’s meaning depends on its stated definition, not only on its short title.

A remission endpoint is used to describe whether participants reached a specified disease-response state within the assessment period. It does not, on its own, describe how long remission lasted, overall survival, or the time taken to reach a response; those are distinct outcomes. Although the registry lists the primary outcome and its timeframe, it does not report the observed CR rate, the number of participants included in its analysis, or an uncertainty interval. The numerical primary-endpoint result is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary percentage endpoint, a phase 1 dose-finding objective, a phase 2 efficacy objective, and a single-group design. It does not report a detailed statistical analysis plan or a numerical result for the primary outcome. The explanations below describe general statistical concepts and distinguish them from methods actually documented for this trial.

What does a percentage endpoint represent?

In general, a percentage for a binary outcome is based on classifying each participant as meeting or not meeting a prespecified event definition. For this trial, the event definition concerns CR, including CRi, assessed within the 12-month timeframe. To interpret a reported percentage, readers would need to know both the number meeting the definition and the number included in the analysis. The registry record does not report either numerator or analysis denominator for the primary endpoint, so its percentage cannot be reconstructed or assessed.

A percentage is a point estimate: it gives one summary of the observed group. It does not show how much sampling uncertainty surrounds that estimate. In general, a confidence interval communicates a range of values compatible with the observed data under the interval’s assumptions. A narrower interval indicates greater precision than a wider interval, but an interval does not eliminate uncertainty or correct weaknesses in design. No primary-outcome confidence interval is reported in the registry record.

Why does the single-group design matter?

In general, a single-group study estimates outcomes among participants who received the study regimen. It does not create a randomized contrast with a separate treatment group. Randomization is a design method that, when properly conducted, supports comparisons by reducing systematic differences between groups. Because this record identifies one group and allocation as not applicable, it does not support a randomized treatment-effect estimate.

A descriptive outcome in one group can be useful for documenting what happened to enrolled participants, but it cannot alone establish what would have happened to those same participants under a different treatment. Historical or external comparisons would require additional information and assumptions; no such comparison is reported in the registry record. The absence of masking also means the design is not described as blinded. The record does not provide further details about assessment procedures that would permit a more specific evaluation of possible measurement influences.

How do the phase objectives differ?

In general, dose-finding work seeks information about tolerability across doses and may identify a maximum tolerated dose under the protocol’s rules. The record states that phase 1 aimed to determine the maximum tolerated dose of lenalidomide after azacitidine. It does not report the dose levels, escalation rules, dose-limiting toxicity definition, or selected maximum tolerated dose. Those details are not reported in the registry record.

The phase 2 objective is described as determining efficacy of the combination, with CR rate as the primary outcome. Efficacy questions generally require a defined endpoint, analysis population, and method for estimating the outcome. The endpoint definition and timeframe are present, but the analysis population, estimator details, and numerical findings are not. The record lists zero analyses, and no detailed statistical plan is reported. It is therefore not possible to identify from this record whether any particular model, adjustment, or inferential procedure was used.

What do planning calculations mean?

In general, sample-size planning asks how many observations may be needed to detect a specified effect under stated assumptions. It is different from analyzing the outcomes observed in a completed trial. The planning assumptions associated with this record describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is the planning quantity; for other illustrations, the quantity is participants per arm.

These assumptions are identified as a planning illustration, not as the trial’s own design. They do not establish that this single-group study planned an equal-allocation comparison, and they do not establish the actual sample-size justification. No such justification is reported in the registry record. Planning calculations are not observed power: they do not show the probability that the completed study detected an effect, nor do they supply a missing endpoint result. No numerical planning output is reported in the registry information.

What can uncertainty and over-dispersion add?

In general, uncertainty measures help readers distinguish a stable estimate from one that could vary substantially with repeated sampling. For a binary percentage, uncertainty depends on the observed event information and the analysis method. A confidence interval is often used to express this uncertainty, while a test may address a specified null hypothesis. Neither an interval nor a test can make a single-group design equivalent to a randomized comparison.

Over-dispersion is a general concern for count or proportion models when observed variability exceeds what the model assumes. If present and ignored, standard errors may be too small and uncertainty may be understated. However, the registry record does not identify a model for the primary endpoint, report an over-dispersion assessment, or state that over-dispersion occurred. This is a general methodological consideration, not a finding about this trial.

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("Azacitidine Followed by Lenalidomide")
n      <- c(43)
events <- c(12)
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  Azacitidine Followed by Lenalidomide  43  12  27.9  15.3  43.7  16.7  42.7  16.8  42.8

11. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary outcome, complete remission rate, assessed over 12 months. It also names secondary outcomes: 4-week survival rate, maximum tolerated dose of lenalidomide, remission duration, overall response rate, overall survival, time to CR, time to PR, and overall survival of responders. Examining multiple outcomes can raise multiplicity concerns in general, because the chance of at least one apparently notable result can increase when many hypotheses are tested.

Whether and how multiplicity was addressed depends on the analysis plan, including which outcomes were confirmatory, whether tests were planned, and whether adjustments or a hierarchy were used. Those details are not reported in the registry record. The record does not report a statistical analysis plan, multiplicity procedure, or numerical analyses for the primary and secondary outcomes. The fact that outcomes are listed does not establish that each was formally tested or that any particular adjustment was applied.

Missing-data handling and analysis populations are also not described. The primary-outcome population field is blank, and the record does not say how participants with unavailable response assessments, withdrawal, or other incomplete follow-up were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population. These omissions matter because a percentage depends on who is included and how missing outcome status is treated. No assumption about those choices should be made from the enrollment total alone.

For survival and time-to-response outcomes, general methods may account for different follow-up durations and censoring, but the registry record does not report the methods used or the number of analyzed events. No statistical analyses are reported in the registry record. The observed findings, their uncertainty, and the treatment of missing observations therefore cannot be evaluated from the listed outcome names alone.

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: febrile neutropenia (55.8%), dyspnea (9.3%), death nos-disease progression (7.0%), death nos-aml disease (4.7%), death nos-cardiopulmonary arrest (4.7%).

The adverse-event entry is for the “Azacitidine Followed by Lenalidomide” group. It reports 43 participants at risk for serious adverse events and 36 affected; for other adverse events it reports 43 at risk and 39 affected. These are descriptive group-level counts. The registry does not provide a comparative arm, so these entries do not estimate a difference between treatments.

The leading serious adverse-event terms are listed with percentages: febrile neutropenia, 55.8%; dyspnea, 9.3%; death NOS-Disease progression, 7.0%; death NOS-AML disease, 4.7%; death NOS-Cardiopulmonary arrest, 4.7%; and death NOS-Death, 4.7%. These are term-specific entries. They should not be added together or read as mutually exclusive categories; the record does not report whether an individual could contribute to more than one term. Nor should a percentage for a specific term be treated as the overall rate of all serious events.

The deaths field is not populated. The listed death-related terms are adverse-event terms and do not, by themselves, provide a complete mortality analysis or establish cause. Timing, exposure duration, event-level details, attribution, and statistical comparisons are not reported in the registry record. The figures therefore describe the safety entries as recorded, without supporting a causal conclusion.

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

The registry record documents a completed early-phase study of azacitidine followed by lenalidomide for previously untreated elderly patients with acute myeloid leukemia. It specifies a phase 1 dose-finding objective and a phase 2 efficacy objective. It also identifies complete remission rate, including CRi, over 12 months as the primary outcome. These details establish what the study set out to investigate and how the primary outcome was described.

They do not establish the observed remission result. The registry record does not report a primary-outcome percentage, the number of participants who met the remission definition, an analysis denominator, or an uncertainty interval. Without those results, the magnitude and precision of the primary outcome cannot be assessed. The study’s completion status and enrollment count do not fill that gap.

The single-group design also means the record does not provide a randomized comparison with another regimen or a control group. Even if an outcome estimate were available, it would describe the study group rather than, by itself, isolate the effect of the regimen relative to an alternative. No claim that the treatment works or does not work follows from the information.

The registry includes descriptive serious and other adverse-event counts and several leading serious-event terms. Those entries can be read as safety information recorded for the treatment group, but they do not establish causation, comparative risk, or a complete account of mortality. The absence of a reported analysis plan, outcome populations, and missing-data methods further limits interpretation.

In short, the record supports conclusions about trial structure, objectives, endpoint definition, enrollment, and the safety entries it lists. It does not support a numerical efficacy conclusion or a controlled estimate of treatment effect. Distinguishing these documented details from unreported outcome analyses is essential when interpreting a registry entry.

14. Why This Trial Matters Statistically

This trial is statistically notable for combining a dose-finding phase with an efficacy-focused phase while using a single-group design. The stated phase 1 objective concerns the maximum tolerated dose of lenalidomide after azacitidine; the phase 2 objective concerns efficacy of the combination. These objectives call for different interpretations. Dose finding is not the same as estimating comparative efficacy, and the existence of both components does not mean that both results are reported.

The primary endpoint is a percentage with a defined timeframe and remission description. This makes clear what kind of outcome was intended, including the inclusion of CRi. But an endpoint definition is only one part of a complete statistical result. Readers also need the observed event information, the analysis population, and a measure of uncertainty to understand the estimate. Those primary-outcome details are not reported in the registry record.

The single-group structure is equally important. It allows descriptive reporting of outcomes among participants in the study, but it does not supply a randomized contrast. This distinction prevents an observed group outcome from being mistaken for a causal estimate of benefit or harm. The registry’s non-masked, single-group description should therefore shape any interpretation of the study’s stated efficacy aim.

Finally, the record illustrates why registry status and results are separate pieces of information. It identifies the study as completed and reports enrollment of 45, but it does not give a numerical primary-endpoint result or detailed statistical analyses. The record remains informative about design and intended measurement even where results are not reported. Statistically careful reading keeps that information useful without treating missing results as evidence for any particular 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.

Several trial-specific limitations follow directly from the registry description. The study is single group, with allocation not applicable and no masking. There is no separate comparator arm reported, so the design does not support a randomized between-group estimate. Any interpretation of outcomes would need to remain descriptive unless additional comparative evidence were available; no such evidence is reported in this registry record.

The primary endpoint is described, but its result is absent. The record does not report the observed CR rate, an analysis denominator, the number meeting the endpoint, or an uncertainty interval. The primary-outcome population field is blank. The definition includes CRi and cites European LeukemiaNet guidelines, while the accompanying definition refers to the absence of clonal lymphocytes in peripheral blood. The registry does not provide further operational detail about how assessments were made.

Important statistical details are also not reported: the analysis plan, methods for missing data, analysis populations, multiplicity approach, dose-escalation rules, and selected maximum tolerated dose. Although a phase 1–2 structure and dose escalation followed by expansion are described, that brief description does not establish the protocol details or how the phase-specific analyses were conducted. Secondary outcomes are named without numerical results.

The safety record supplies affected counts and leading serious-event terms, but does not report event timing, exposure duration, attribution, or a comparative safety analysis. A deaths field is not populated. These gaps limit assessment of how the safety entries relate to treatment exposure and follow-up. The record’s enrollment total alone cannot resolve these limitations or substitute for the missing outcome and analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML) — NCT00890929.
• Registry record last updated 2018-06-18; status last verified 2018-05.
• Results first posted 2014-10-20.
• 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

NCT00890929 is listed as a completed phase 1–2 study sponsored by Stanford University, with enrollment of 45. The study evaluated azacitidine followed by lenalidomide in previously untreated elderly patients with acute myeloid leukemia. Its design is single group, allocation is not applicable, and masking is listed as none. The arm description specifies dose escalation followed by dose expansion.

The phase 1 objective was to determine the maximum tolerated dose of lenalidomide after azacitidine. The phase 2 objective was to assess efficacy. Complete remission rate, including CRi, over 12 months is the primary outcome. Secondary outcomes include survival, remission duration, overall response, and time-to-response measures.

The registry record does not report a numerical primary-endpoint result, a detailed statistical analysis plan, analysis populations, or missing-data methods. It does list serious and other adverse-event counts and leading serious-event terms for the treatment group. These entries are descriptive and do not constitute a controlled comparison.