This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia (NCT00136084), a randomized phase 3 study. The primary outcome is Minimal Residual Disease (MRD)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00136084 |
| Phase | Phase 3 |
| Condition | Leukemia, Myelocytic, Acute |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 238 |
| Arms in the primary outcome | n/a |
| Lead sponsor | St. Jude Children's Research Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Patients with newly diagnosed acute myeloid leukemia or myelodysplasia. The registry record reports 223 randomized patients; 205 were included in the day 22 minimal residual disease analysis.
Intervention
The high-dose cytarabine strategy, identified as HDAC. The record lists cladribine, cyclophosphamide, cytarabine, daunorubicin, and dexamethasone among the interventions, but the arm description directs readers to a detailed description that is not included in the available record.
Comparator
The low-dose cytarabine strategy, identified as LDAC. The record lists etoposide, cytarabine, gemtuzumab, L-asparaginase, mercaptopurine, methotrexate, mitoxantrone, prednisone, and vincristine among the interventions. The available arm description does not provide the full regimen details.
Primary question
After one course of chemotherapy, what was the day 22 minimal residual disease status, where positive status was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (≥0.1%)? The registry record does not report the arm-level results for this endpoint, so it does not establish which strategy had more MRD-positive or MRD-negative patients.
The trial is described as a comparison of two multi-agent chemotherapy regimens using different cytarabine dosages. The primary endpoint asks whether detectable leukemia remained after one course, using a specified threshold in a bone-marrow sample. This is a response measure at a particular assessment time, not a direct summary of longer-term disease control or survival.
The record also lists secondary questions about MRD changes after treatment courses, toxicity, event-free survival, inhibition of DNA synthesis, and the relationship between that inhibition and clinical response. Those questions broaden the scientific aims, but the endpoint results and the statistical comparisons needed to answer them are not reported in the registry record.
3. Trial Design
This was a phase 3, randomized, parallel-group trial with no masking. The registry record describes the study as a collaborative trial for patients with newly diagnosed acute myeloid leukemia or myelodysplasia. Its stated purpose was to compare multi-agent chemotherapy regimens that used different dosages of cytarabine.
The two groups are labeled HDAC, for high-dose cytarabine, and LDAC, for low-dose cytarabine. The intervention listings name several chemotherapy agents, but the short arm descriptions refer readers to detailed descriptions rather than specifying the complete treatment schedules. Dosing schedules, treatment sequence, and rules for changing treatment are not reported in the registry record.
The record gives an enrollment of 238 and separately states that 223 patients were randomized. These are distinct counts in the record; their difference should not be interpreted as a particular screening or eligibility outcome without further information. For the day 22 MRD analysis, 205 of the randomized patients were included. Reasons recorded for non-inclusion include inadequate samples, absence of a suitable phenotype, an MRD assessment not done, and a patient listed as lost. The analysis population therefore does not include every randomized patient.
The primary endpoint is MRD measured on day 22, following one course of chemotherapy. The trial record lists additional outcomes that include toxicity and event-free survival, as well as laboratory measures related to DNA synthesis. The record labels the study completed, but completion status alone does not provide the results or indicate how precise the treatment comparison was.
Details needed to reconstruct the design more fully—including the allocation procedure, the intended sample-size justification, and the full regimen descriptions—are not reported in the registry record. Randomization supports a planned comparison between groups, but interpretation of the observed results would also require the outcome counts, analysis methods, and handling of missing assessments.
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.
Before assignment: 238 patients were enrolled on the study. This report is based on results for 223 patients. 15 patients were excluded for the following reasons: 7 were switched to lymphoid-directed therapy shortly after enrollment, 6 were determined to be ineligible shortly after enrollment (wrong diagnosis), and 2 were not randomized.
Overall Study
| Stage | Arm 1: (HDAC) | Arm 2:(LDAC) |
|---|---|---|
| STARTED | 109 | 114 |
| COMPLETED | 61 | 72 |
| NOT COMPLETED | 48 | 42 |
Reasons for not completing this period:
| Reason | Arm 1: (HDAC) | Arm 2:(LDAC) |
|---|---|---|
| Death | 12 | 5 |
| Unacceptable toxicity | 8 | 11 |
| Relapse | 20 | 23 |
| Lost to Follow-up | 2 | 0 |
| No Response | 1 | 2 |
| Withdrawal by Subject | 5 | 1 |
Analysis population for the primary outcome, as defined in the registry: Of the 223 randomized patients, 205 patients were included in the day 22 MRD analysis. 18 patients were not included in the day 22 MRD analysis. 5 patients had inadequate sample for MRD, 11 patients had no suitable phenotype to determine MRD, 1 patient was not done on MRD, and 1 patient was lost for follow-up.
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.
| Characteristic | Unit | Arm 1: (HDAC) | Arm 2:(LDAC) | Total |
|---|---|---|---|---|
| Participants analysed | 109 | 114 | 223 | |
| Age Continuous | years | 8.57 (SD 6.08) | 8.48 (SD 6.32) | 8.49 (SD 6.19) |
| Sex: Female, Male: Female | Participants | 50 | 48 | 98 |
| Sex: Female, Male: Male | Participants | 59 | 66 | 125 |
6. Primary Endpoint
The registry lists the primary outcome as Minimal Residual Disease (MRD)., measured over Day 22 MRD measurement.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is minimal residual disease status measured on day 22, following one course of chemotherapy. MRD is a measure of whether leukemic cells remain detectable in the bone-marrow sample under the study’s stated assay definition. A positive result was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (≥0.1%). The endpoint is expressed as a number of participants.
MRD is used as an early response measure because it distinguishes patients with detectable disease from those without detectable disease at the specified assessment. This is a threshold-based classification: a result on one side of the stated cutoff is categorized differently from a result on the other side. It does not mean that every cell has been assessed throughout the body, nor does a negative result establish that disease can never recur.
For a randomized comparison, arm-level counts and the analysis comparing those counts would be needed to describe how MRD status differed between treatment strategies. The registry record does not report those primary endpoint results. It therefore does not support a numerical estimate of the treatment contrast, its uncertainty, or a conclusion about the direction of the comparison.
MRD status is also distinct from the listed secondary outcomes, such as event-free survival and toxicity. A response measure at day 22 cannot by itself answer questions about later clinical outcomes or adverse effects. Those require their own results and definitions, which are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary scientific question is whether day 22 MRD status differed between the high-dose and low-dose cytarabine strategies after one course of chemotherapy. The registry record identifies the endpoint, defines MRD positivity, and reports that 205 randomized patients were included in its analysis. It does not give the numbers of MRD-positive or MRD-negative patients in either arm, nor does it report a treatment comparison, confidence interval, or p-value for this endpoint.
As a result, the direction and size of the primary treatment contrast cannot be described from the record. It is not possible to say whether one arm had more patients with detectable MRD, how large any difference was, or how precisely it was estimated. These are absences of reported results, not evidence that the arms had the same outcomes.
The record states that 223 patients were randomized and 205 entered the day 22 MRD analysis. The record identifies 18 patients who were not included, with reasons listed as inadequate MRD samples, no suitable phenotype to determine MRD, an assessment not done, and one patient listed as lost. The available description does not give further detail for the lost patient. Exclusion from this endpoint analysis can matter because the observed analysis group may not represent all randomized patients in the same way in both arms. Arm-specific missingness and the method used to handle it are not reported in the registry record.
The registry record lists secondary outcomes concerning MRD conversion or reduction, toxicity, event-free survival, and DNA synthesis. Listing an outcome is not the same as reporting its findings. No effect estimates or uncertainty measures for those outcomes are included in the record, so they cannot be used to supplement the missing primary comparison.
General statistical interpretation: a confidence interval describes a range of values reasonably compatible with the data and analysis, rather than giving a guarantee that the true value lies in that range. Without a reported estimate and interval, the precision of a treatment comparison cannot be assessed. Likewise, a p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not by itself describe clinical importance. Neither type of result is reported for the primary endpoint in the registry record.
The trial’s completed status and its randomized design are relevant context, but neither supplies the missing endpoint results. The record supports describing the comparison that was planned and the analysis population that was reported. It does not support a claim that either regimen had a better or worse MRD result.
9. Statistical Methods Explained
The registry record identifies the primary measure as a number of participants and describes the endpoint as binary MRD status: positive or negative according to the stated detection threshold. For a binary endpoint, the basic descriptive information is the count in each category within each treatment group. A comparison can then express how the distribution differs between groups, using an analysis appropriate to the trial design and the endpoint. The arm-level counts and the inferential analysis are not reported in the registry record.
What does randomization contribute?
General statistical explanation: randomization is intended to make treatment assignment independent of participants’ baseline characteristics, on average, so that a between-group comparison can estimate the effect of assignment to the treatment strategies. It does not guarantee that every characteristic is balanced in a particular trial, and it does not resolve problems caused by missing outcome measurements, treatment deviations, or incomplete reporting. The record identifies the trial as randomized but does not report the allocation procedure or the analysis population rules in detail.
How should an effect estimate be read?
General statistical explanation: an effect estimate summarizes the observed contrast between groups on a chosen scale. For a binary outcome, possible scales include differences in proportions or relative measures, but the appropriate scale depends on the analysis and question. No primary endpoint estimate or chosen effect scale is reported in the registry record. A numerical contrast cannot therefore be reconstructed or interpreted from the information available.
A confidence interval is useful because it shows the uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, while both the interval and estimate need to be considered in context. A p-value is not a measure of effect size or precision. Neither confidence intervals nor p-values for the primary comparison are reported in the registry record.
What can the sample-size illustrations tell readers?
General statistical explanation: sample-size planning asks how many participants or events would be needed to detect a specified effect under stated assumptions. The planning description associated with this trial uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, and defines the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning convention is participants per arm; time-to-event planning is described in terms of total events using the Schoenfeld method.
These are planning illustrations based on an observed effect, not the trial’s own design justification. They do not show that the trial had a particular probability of detecting an effect after the fact, and they should not be described as observed power. The registry record does not report a sample-size justification for the original trial. The numerical outputs of any planning illustrations are not stated in the record details, so no particular required sample size can be interpreted.
Why does missingness matter?
General statistical explanation: when outcomes are missing, an analysis of participants with observed measurements can be biased if the chance of measurement being missing is related to treatment or outcome status. The consequences depend on why measurements are absent and whether missingness differs between groups. Here, the registry record says 205 of 223 randomized patients were included in the day 22 MRD analysis and lists several reasons for non-inclusion. It does not report an imputation method, sensitivity analysis, or comparison of missingness by treatment arm.
What does multiplicity mean?
General statistical explanation: when several outcomes or statistical tests are examined, the chance of at least one apparently unusual result can increase if the tests are treated as independent opportunities for discovery. A prespecified testing hierarchy or adjustment can address some multiplicity concerns, but the choice depends on the scientific aims and analysis plan. The registry record lists multiple secondary outcomes and analyses, but does not report a multiplicity strategy, testing hierarchy, or complete statistical analysis plan. The number of outcomes alone is not enough to determine what adjustment, if any, was appropriate.
Because primary results and analysis details are absent, the record permits a description of the endpoint and design, but not a statistical appraisal of the treatment effect. Any interpretation of precision, significance, or robustness would require results and methods that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record names the day 22 MRD measure as the primary endpoint and lists secondary questions involving MRD change, toxicity, event-free survival, DNA synthesis inhibition, and the relationship between inhibition and clinical response. It also reports seven outcome measures and six analyses. The relationship among those measures and analyses, including which tests were planned and how they were ordered, is not reported in the registry record.
When a study examines several outcomes or performs multiple tests, multiplicity can affect how results should be interpreted. General statistical explanation: a prespecified testing hierarchy or adjustment can help control the chance of false-positive findings across a family of tests. The registry record does not report whether such an approach was used. The list of outcomes by itself does not show whether all outcomes were tested, which were confirmatory, or whether any adjustment was applied.
For the day 22 MRD analysis, 205 of 223 randomized patients were included. The record identifies 18 patients who were not included: five had inadequate samples for MRD, 11 had no suitable phenotype to determine MRD, one MRD assessment was not done, and one patient was listed as lost. Further detail about the lost patient is not reported in the registry record. The record does not state the arm distribution of these missing assessments or describe an imputation or sensitivity-analysis method.
These details matter because excluding participants with missing outcomes can affect a randomized comparison, particularly if missingness is associated with treatment assignment or disease status. The record does not report whether the primary analysis followed an intention-to-treat approach, how participants were assigned to analysis populations, or whether missing outcomes were handled in a way intended to preserve the randomized comparison. The statistical analysis plan is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm 1: (HDAC) | 23 | 109 | 21.1% |
| Arm 2:(LDAC) | 19 | 114 | 16.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1: (HDAC) | 107 of 109 |
| Arm 2:(LDAC) | 112 of 114 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1: (HDAC) | Arm 2:(LDAC) |
|---|---|---|---|
| Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e | Infections and infestations | 13 of 109 | 10 of 114 |
| Hypokalemia | Metabolism and nutrition disorders | 6 of 109 | 4 of 114 |
| Anorexia | Gastrointestinal disorders | 5 of 109 | 3 of 114 |
| Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe | Infections and infestations | 1 of 109 | 4 of 114 |
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | 3 of 109 | 0 of 114 |
| Pulmonary-Other | Respiratory, thoracic and mediastinal disorders | 0 of 109 | 3 of 114 |
| Renal failure | Renal and urinary disorders | 3 of 109 | 0 of 114 |
| CNS hemorrhage/bleeding | Nervous system disorders | 0 of 109 | 2 of 114 |
| Diarrhea patients without colostomy | Gastrointestinal disorders | 0 of 109 | 2 of 114 |
| Hypotension | Cardiac disorders | 2 of 109 | 0 of 114 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1: (HDAC) | Arm 2:(LDAC) |
|---|---|---|---|
| Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e | Infections and infestations | 83 of 109 | 82 of 114 |
| Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe | Infections and infestations | 69 of 109 | 92 of 114 |
| Hypokalemia | Metabolism and nutrition disorders | 37 of 109 | 38 of 114 |
| Diarrhea patients without colostomy | Gastrointestinal disorders | 21 of 109 | 20 of 114 |
| Anorexia | Gastrointestinal disorders | 23 of 109 | 16 of 114 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 19 of 109 | 17 of 114 |
| Stomatitis/pharyngitis (oral/pharyngeal mucositis) | Gastrointestinal disorders | 15 of 109 | 19 of 114 |
| Allergic reaction/hypersensitivity (including drug fever) | Immune system disorders | 17 of 109 | 16 of 114 |
| Hypotension | Cardiac disorders | 11 of 109 | 20 of 114 |
| Vomiting | Gastrointestinal disorders | 14 of 109 | 15 of 114 |
Serious events with the highest arm-level rate: infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (anc <1.0 x 10e (11.9%), hypokalemia (5.5%), anorexia (4.6%), febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe (3.5%), pneumonitis/pulmonary infiltrates (2.8%).
The serious adverse event figures list 109 participants at risk in the HDAC group, with 23 affected, and 114 participants at risk in the LDAC group, with 19 affected. These are reported as group counts. They describe the listed serious-event measure, but the registry record does not provide a statistical comparison, uncertainty interval, or detailed time period for these counts.
The other adverse-event figures list 109 at risk and 107 affected in HDAC, and 114 at risk and 112 affected in LDAC. The registry record does not provide enough definition in the described information to determine the precise relationship between this measure and the serious-event measure. The counts should therefore be read as separate reported entries, not combined or interpreted as mutually exclusive categories.
The record also lists serious adverse event terms with percentages, including infection with grade 3 or 4 neutropenia, hypokalemia, anorexia, febrile neutropenia, pneumonitis or pulmonary infiltrates, and renal failure. It does not report the denominator for these term percentages or clearly attribute each listed percentage to a treatment arm. They should not be treated as arm-specific risks or compared across arms without that information.
Adverse-event counts describe reported events or affected participants under the record’s definitions; they do not by themselves establish that treatment caused an event. Definitions, observation windows, event-level detail, and comparative safety analyses are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, parallel-group comparison was conducted between high-dose and low-dose cytarabine strategies, with day 22 MRD status named as the primary endpoint. It also identifies the threshold used to define MRD positivity and reports how many randomized patients were included in that endpoint analysis. These details explain what the trial set out to measure and the population represented in the reported MRD analysis.
The record does not report the primary endpoint counts by arm or an estimated treatment contrast. It therefore does not show whether MRD status differed between the strategies, the direction or size of any difference, or how precisely a difference was estimated. The absence of a reported comparison is not evidence of no difference, and it cannot be used to conclude equivalence.
The listed secondary outcomes show that the trial addressed questions beyond early MRD status, including toxicity and event-free survival. However, outcome names are not findings. Without the corresponding results, it is not possible to infer longer-term outcomes or to use those secondary measures to resolve the primary comparison.
General statistical explanation: even when a study reports a difference, the estimate needs to be considered alongside uncertainty, the endpoint’s definition, missing data, and the analysis population. A result may be imprecise even when it appears different, and a result that is not statistically distinguishable from no difference does not prove the treatments are identical. No estimates or uncertainty measures for the primary outcome are reported in the registry record.
The serious-event counts provide some descriptive safety information, but their interpretation is limited by absent definitions and comparative analyses. They do not establish causation, and the term percentages cannot be interpreted as arm-specific risks from the information reported. Overall, the registry record describes the study question and selected design and safety details, but it does not provide enough outcome information to draw a statistical conclusion about comparative efficacy or safety.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a clearly stated endpoint and an absent endpoint result. The registry record defines day 22 MRD positivity using a bone-marrow threshold and reports the number included in the analysis. Yet without the arm-level counts or a treatment-effect estimate, the central randomized comparison cannot be evaluated. This illustrates why endpoint definitions and outcome results are both necessary for interpretation.
The reported analysis population also makes missingness visible. Although 223 patients were randomized, 205 were included in the day 22 MRD analysis. Reasons for non-inclusion are partly itemized, but arm-specific missingness and the approach to incomplete measurements are not reported. In a randomized study, retaining the comparison created by random assignment and understanding exclusions are important to assessing whether the estimate answers the intended question.
The registry lists multiple secondary outcomes and analyses, which raises a general issue of multiplicity. Without a reported analysis plan or testing strategy, readers cannot tell how primary and secondary questions were prioritized or how multiple tests were handled. This is a limitation in interpreting any reported findings, and the primary findings themselves are not reported in the record.
The safety entries also demonstrate the difference between counts and comparative evidence. Group counts and listed percentages are useful descriptions, but their interpretation depends on definitions, denominators, observation periods, and statistical comparisons. Those details are not all reported.
More broadly, this record shows that design information alone does not answer a treatment question. Randomization, endpoint definitions, participant flow, outcome estimates, uncertainty, and analysis methods each contribute a different part of the evidence needed for a statistical reading.
14. 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 main limitation for interpreting this trial is that the registry record does not report the primary day 22 MRD results by treatment group. It therefore contains no endpoint contrast, confidence interval, or p-value with which to assess the comparative result. The presence of a defined primary endpoint and a completed status does not fill this gap.
The reported total enrollment is 238, while the record separately states that 223 patients were randomized. It does not explain the relationship between these counts. The primary MRD analysis includes 205 randomized patients, and the record lists reasons for the 18 patients not included. It does not report the distribution of missing assessments between arms, additional detail for the patient listed as lost, or the method used to address missing outcome data.
Regimen detail is limited in the short arm descriptions, which refer readers to detailed descriptions that are not included in the available record. The complete treatment schedules and any treatment changes are not reported. The allocation procedure beyond the statement that the trial was randomized is not reported, nor is a detailed statistical analysis plan.
The record lists secondary outcomes and analyses but does not report a multiplicity strategy, testing hierarchy, or results for those measures. The serious adverse event entries lack enough detail in the reported information to establish event definitions, observation periods, and arm-specific denominators for the listed term percentages. These limits constrain both safety and efficacy interpretation.
Finally, the registry record does not report the trial’s sample-size justification. Planning illustrations based on observed effects do not substitute for that design rationale or for reported outcome estimates.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia — NCT00136084.
- Registry record last updated 2012-12-05; status last verified 2012-11.
- Results first posted 2010-03-26.
- 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.
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18. Record Summary
The registry record describes a completed phase 3, randomized, unmasked, parallel-group study comparing high-dose and low-dose cytarabine strategies for newly diagnosed acute myeloid leukemia or myelodysplasia. It reports enrollment of 238, states that 223 patients were randomized, and identifies day 22 MRD status after one course of chemotherapy as the primary endpoint.
MRD positivity was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (≥0.1%). The record states that 205 randomized patients were included in the MRD analysis and gives several reasons why 18 were not included. It also lists secondary outcomes involving MRD, toxicity, event-free survival, and DNA synthesis.
Serious adverse event counts are reported for both treatment groups, along with selected event terms and percentages. The primary endpoint results, detailed comparative analyses, missing-data methods, multiplicity approach, full regimen descriptions, and statistical analysis plan are not reported in the registry record.