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 A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL (NCT01483690), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01483690 |
| Phase | Phase 1, Phase 2 |
| Condition | Acute Lymphoblastic Leukemia, Precursor B-Cell Lymphoblastic Leukemia, Precursor T-Cell Lymphoblastic Leukemia |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 23 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Therapeutic Advances in Childhood Leukemia Consortium |
| Results posted | Yes |
2. Clinical Question
The study concerns pediatric patients with relapsed acute lymphoblastic leukemia (ALL), including precursor B-cell and precursor T-cell lymphoblastic leukemia. Its central clinical-trial question was whether decitabine and vorinostat could be given before and during chemotherapy while monitoring side effects, particularly dose-limiting toxicity (DLT), over 6 weeks. The registry record identifies participants who entered the study as the primary endpoint population.
Population
Pediatric patients with relapsed ALL. The listed conditions include acute lymphoblastic leukemia, precursor B-cell lymphoblastic leukemia, and precursor T-cell lymphoblastic leukemia.
Intervention
Decitabine and vorinostat were used before and during chemotherapy. The chemotherapy drugs named in the study description are vincristine, dexamethasone, mitoxantrone, and peg-asparaginase. Methotrexate is also listed among the interventions.
Comparator
No randomized control group is described. The record lists an Initial Dose Level and a Modified Dose Level, but the study is non-randomized and these are not like-for-like control groups.
Primary question
How many participants experienced a DLT during the 6-week primary endpoint timeframe? The registry record gives the endpoint definition, but the number of participants with a DLT is not reported in the registry record.
3. Trial Design
This was a Phase 1 and Phase 2 pilot study with a non-randomized, single-group model and no masking. The registry lists an enrollment of 23. It names two dose levels: Initial Dose Level and Modified Dose Level. Because allocation was non-randomized, the dose-level groups should not be treated as randomized treatment and control arms, or as directly comparable groups for estimating a causal treatment effect.
At the Initial Dose Level, decitabine was described as 15 mg/m2/day by intravenous infusion over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat was described as 180 mg/m2/day, with a maximum dose of 400 mg daily, orally on days 3 through 10 and days 17 through 24. At the Modified Dose Level, decitabine was described as 10 mg/m2/day by intravenous infusion over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat was described as 180 mg/m2/day, with a maximum dose of 400 mg daily, orally on days 2 through 7 and days 16 through 21.
The study description places these drugs before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase. The registry also lists methotrexate as an intervention, but its schedule is not reported in the registry record. The record lists a start date of 2011-12, primary completion on 2015-07-31, and status as terminated. The reason for termination and the rationale for changing dose levels are not reported in the registry record.
With no random assignment or comparator group, the design is suited to describing tolerability and recorded outcomes in the study participants. It cannot, by itself, separate treatment effects from differences between participants, changes in care over time, or other influences. The registry record does not report the statistical plan or explain whether the dose-level groups were enrolled in a particular sequence.
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
| Stage | Initial Dose Level | Modified Dose Level |
|---|---|---|
| STARTED | 5 | 18 |
| COMPLETED | 3 | 13 |
| NOT COMPLETED | 2 | 5 |
Reasons for not completing this period:
| Reason | Initial Dose Level | Modified Dose Level |
|---|---|---|
| Adverse Event | 1 | 2 |
| clinical deterioration | 1 | 0 |
| Physician Decision | 0 | 2 |
| exclusionary procedure | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants who entered the 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.
Population: Total number of participants enrolled into the study.
| Characteristic | Unit | Initial Dose Level | Modified Dose Level | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 18 | 23 | |
| Age, Continuous | years | 12.5 (4.9 to 14.5) | 12.0 (1.6 to 21.4) | 12.0 (1.6 to 21.4) |
| Sex: Female, Male: Female | Participants | 2 | 4 | 6 |
| Sex: Female, Male: Male | Participants | 3 | 14 | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 9 | 12 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 9 | 11 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 2 | 2 |
| Race (NIH/OMB): White | Participants | 5 | 10 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 5 | 5 |
| CNS Status: CNS 1 | Participants | 4 | 14 | 18 |
| CNS Status: CNS 2 | Participants | 1 | 2 | 3 |
| CNS Status: CNS 3 | Participants | 0 | 2 | 2 |
| Prior hematopoietic cell transplantation (HCT): Yes had prior HCT | Participants | 3 | 8 | 11 |
| Prior hematopoietic cell transplantation (HCT): No did not have prior HCT | Participants | 2 | 10 | 12 |
| Relapse # at enrollment: 2nd Relapse | Participants | 2 | 13 | 15 |
| Relapse # at enrollment: 3rd Relapse | Participants | 1 | 1 | 2 |
| Relapse # at enrollment: Refractory | Participants | 2 | 4 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)., measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants who experienced a dose-limiting toxicity (DLT), with a timeframe of 6 weeks. The population is described as participants who entered the study. This is a count endpoint: it records how many participants met the study's DLT definition, rather than measuring the severity of symptoms on a continuous scale or the time until an event.
In general, DLT monitoring is used in early-phase drug studies to assess whether treatment-related side effects limit the ability to give a planned regimen. The endpoint can inform evaluation of a dose or combination, but interpretation depends on the protocol's definition of a DLT, the observation window, which participants are evaluable, and how missing follow-up is handled. Those operational details are not reported in the registry record.
The registry record states that the endpoint was intended to evaluate side effects from decitabine and vorinostat given before and during chemotherapy. It does not report the number of participants who experienced a DLT, a DLT rate, or an estimate of uncertainty around the endpoint. The adverse-event summaries are separate safety information and cannot substitute for the primary endpoint result: a serious adverse event is not necessarily a DLT, and the record does not identify which listed events met the DLT definition.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record establishes the study question and design, but it does not provide the primary endpoint result. Although the endpoint is defined as the number of participants who experienced a DLT during 6 weeks, the corresponding count is not reported in the registry record. No confidence interval, test result, or analysis of that endpoint is reported. Consequently, the record does not permit an estimate of the frequency or precision of DLT in this study.
The registry reports enrollment of 23 and names Initial Dose Level and Modified Dose Level groups. The design is non-randomized, so differences between these groups would not have the same interpretation as differences between randomly assigned groups. The groups could differ in participant characteristics, timing, or other factors; the registry record does not describe enough about allocation to assess those possibilities. They should not be treated as a controlled comparison of dose levels.
The safety entries list 5 participants at risk and 5 affected at the Initial Dose Level, and 18 participants at risk and 18 affected at the Modified Dose Level for serious adverse events. Death counts are listed as 5 and 13, respectively. These are safety summaries, not the primary DLT result. The record does not report causes or timing of deaths, their relationship to study treatment, or whether any death met the DLT definition. The listed serious-event terms include anemia at 61.1%, hypokalemia at 50.0%, and lymphocyte count decreased, neutrophil count decrease, platelet count decreased, and sepsis each at 40.0%. The denominators and group attribution for these term percentages are not reported in the registry record, so they should not be interpreted as directly comparable risks between dose levels.
There is also a secondary outcome titled Disease Response Rate After Treatment, but its result is not reported in the registry record. No analyses are listed. This leaves no posted treatment-response estimate and no statistical basis for comparing response between dose levels or with another treatment.
In general, a confidence interval communicates the range of values compatible with an estimate under the statistical model and data. Without an endpoint estimate and interval, precision cannot be assessed. The absence of a reported analysis is not evidence that no events occurred; it means the registry record does not provide the result needed to describe them. The available information supports a description of the study's design, endpoint, and recorded safety summaries, but not a conclusion about treatment efficacy or comparative safety.
9. Statistical Methods Explained
The study is described as non-randomized and single-group, with no masking. These design features shape what statistical conclusions are possible. Randomization, in general, helps balance measured and unmeasured participant characteristics across groups. Because allocation was non-randomized, comparisons between the Initial Dose Level and Modified Dose Level cannot be interpreted as though treatment assignment had been randomized. The record also does not describe a separate control group.
What does a count endpoint represent?
The primary endpoint is a count of participants experiencing a DLT within 6 weeks. A count is a direct summary of how many participants met an outcome definition. To interpret it fully, readers would also need the denominator used for analysis, the DLT criteria, and rules for participants with incomplete observation. The record describes the population as participants who entered the study, but does not report the DLT count or those operational details. Without the result and a clear analysis denominator, neither an event frequency nor its precision can be assessed.
Why does the observation window matter?
An endpoint timeframe determines which events contribute to the outcome. Here, the primary timeframe is 6 weeks. In general, a fixed observation window makes the outcome interpretable only for events captured within that window; events outside it do not answer the same question. The record does not report whether every participant completed the window, how early withdrawal was handled, or whether any participants were excluded from the primary endpoint analysis.
How should uncertainty be understood?
In general, a confidence interval expresses uncertainty around an estimated quantity under the chosen statistical method. It is not a guarantee that the true value lies within a particular interval. For a participant-count outcome, the event count and the analysis population are needed before an interval can be interpreted. No primary endpoint estimate or confidence interval is reported in the registry record, so the precision of the DLT result cannot be evaluated.
What can the two dose levels establish?
The record names an Initial Dose Level and a Modified Dose Level and gives different schedules for decitabine and vorinostat. In a non-randomized study, dose-level differences may reflect more than dose: participant mix, timing, eligibility, clinical decisions, or other changes could also contribute. The registry record does not report the allocation process, the reason for the modification, or an adjusted analysis. A numerical difference between groups, if one were available, would therefore be descriptive rather than a clean estimate of a causal dose effect.
What is the role of the safety summaries?
The serious adverse-event entries count participants at risk and participants affected by group. The record also lists deaths and the percentages attached to selected serious-event terms. In general, adverse-event summaries describe events recorded during a study, but interpretation depends on definitions, follow-up, attribution, and denominators. The record does not state whether each event was considered related to treatment, nor does it connect the listed serious events to the DLT definition. These entries therefore cannot be used as a substitute for the primary endpoint analysis.
The planning assumptions described in the record refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects framed as fractions of an observed effect. Such calculations are planning illustrations, not evidence of observed power. Their assumptions do not make the non-randomized dose-level groups equivalent to randomized arms. The record does not report a sample-size justification for the trial's own design, and the primary endpoint result needed to evaluate an observed effect is not reported.
Finally, the registry lists zero analyses. The statistical analysis plan, handling of multiplicity, missing-data methods, and analysis populations are not reported in the registry record. These omissions limit reproducibility: readers cannot determine which participants contributed to each outcome, which comparisons were prespecified, or how uncertainty was quantified. The methods that can be described are therefore limited to the registered design and endpoint, not an unreported analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint for DLT and a secondary outcome for disease response rate after treatment. It does not report statistical analyses for either outcome, and it does not describe a multiplicity strategy. In general, testing multiple outcomes or comparisons can increase the chance of finding an apparently notable result by chance; a prespecified approach can clarify how that issue is handled. No such approach is reported in the registry record.
Missing-data handling is also not reported in the registry record. The primary endpoint population is described as participants who entered the study, but the record does not explain how participants with incomplete observation, early withdrawal, or unavailable outcome information were treated. Without those rules, it is not possible to determine the analysis denominator or assess whether missing observations could affect interpretation.
The registry record does not report an analysis population, such as a defined evaluable group, nor does it report a statistical analysis plan. It also does not provide an endpoint result or any analysis estimates. The enrollment field lists 23, but that alone does not establish how many participants contributed to each outcome. These gaps mean that neither the endpoint analysis nor the handling of multiple outcomes and missing observations can be independently evaluated from 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 |
|---|---|---|---|
| Initial Dose Level | 5 | 5 | 100.0% |
| Modified Dose Level | 18 | 18 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Initial Dose Level | 5 of 5 |
| Modified Dose Level | 13 of 18 |
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 |
|---|---|
| Initial Dose Level | 5 of 5 |
| Modified Dose Level | 18 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | Initial Dose Level | Modified Dose Level |
|---|---|---|---|
| Anemia | Metabolism and nutrition disorders | 1 of 5 | 11 of 18 |
| Hypokalemia | Metabolism and nutrition disorders | 2 of 5 | 9 of 18 |
| platelet count decreased | Blood and lymphatic system disorders | 2 of 5 | 7 of 18 |
| white blood cell decreased | Blood and lymphatic system disorders | 2 of 5 | 6 of 18 |
| neutrophil count decrease | Blood and lymphatic system disorders | 2 of 5 | 5 of 18 |
| sepsis | Infections and infestations | 2 of 5 | 4 of 18 |
| Lymphocyte count decreased | Metabolism and nutrition disorders | 2 of 5 | 2 of 18 |
| Alkaline phosphatase increased | Metabolism and nutrition disorders | 0 of 5 | 3 of 18 |
| Blood bilirubin increased | Metabolism and nutrition disorders | 1 of 5 | 2 of 18 |
| Lipase increased | Metabolism and nutrition disorders | 1 of 5 | 2 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Initial Dose Level | Modified Dose Level |
|---|---|---|---|
| Febrile neutropenia | Infections and infestations | 2 of 5 | 15 of 18 |
| Anemia | Blood and lymphatic system disorders | 1 of 5 | 15 of 18 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 5 | 5 of 18 |
| Hypokalemia | Metabolism and nutrition disorders | 2 of 5 | 5 of 18 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 5 | 5 of 18 |
| Hypophosphatemia | Metabolism and nutrition disorders | 1 of 5 | 6 of 18 |
| Anorexia | General disorders | 2 of 5 | 4 of 18 |
| Blood bilirubin increased | Blood and lymphatic system disorders | 1 of 5 | 5 of 18 |
| Aspartate aminotransferase increased | Metabolism and nutrition disorders | 1 of 5 | 4 of 18 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 5 | 3 of 18 |
Serious events with the highest arm-level rate: anemia (61.1%), hypokalemia (50.0%), lymphocyte count decreased (40.0%), neutrophil count decrease (40.0%), platelet count decreased (40.0%).
The serious adverse-event summary lists the Initial Dose Level with 5 participants at risk and 5 affected, and the Modified Dose Level with 18 at risk and 18 affected. The death counts listed for these groups are 5 and 13, respectively. These are counts as recorded in the registry, not estimates from a randomized comparison. Because the study was non-randomized, the groups should not be read as comparable treatment and control arms.
The selected serious-event terms and percentages are anemia at 61.1%, hypokalemia at 50.0%, and lymphocyte count decreased, neutrophil count decrease, platelet count decreased, and sepsis each at 40.0%. The registry record does not report the denominators for these percentages or their attribution to a particular dose-level group. It also does not report event timing, causes of death, treatment relationship, or whether any event met the DLT definition. The safety summaries describe recorded events; they do not establish that a treatment caused an event or provide the missing primary DLT result.
12. What the Result Does, and Does Not, Mean
The record documents a pilot study of decitabine and vorinostat given before and during chemotherapy in pediatric patients with relapsed ALL. It identifies two dose levels, a non-randomized single-group design, enrollment of 23, and a primary DLT endpoint assessed over 6 weeks. It also presents serious adverse-event and death counts, along with selected serious-event terms and percentages.
What the record does not establish is equally important. It does not report the number of participants who experienced a DLT, the disease response rate, or statistical analyses. It therefore cannot show the size or precision of either primary or secondary outcome results. Nor can the non-randomized dose-level groups establish a causal comparison between dose regimens. A registry listing of serious events does not by itself show that study treatment caused those events, and the record does not report their relationship to treatment.
In general, a pilot study can provide descriptive information about a regimen and help frame questions for later research. That role does not convert a small, non-randomized study into a definitive efficacy comparison. The registry record's terminated status is reported, but its reason is not reported in the registry record. No interpretation of that status as a safety, efficacy, feasibility, or administrative decision is justified from the available information.
The most supportable reading is therefore descriptive: the study evaluated a combination regimen and registered a toxicity-focused primary endpoint, while posting selected safety summaries. The absence of endpoint results and analysis limits any further conclusion. Neither benefit nor lack of benefit can be inferred from an outcome that is not reported.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting details matter when interpreting early-phase clinical research. A DLT count is directly relevant to a toxicity-focused question, but it cannot be interpreted without the outcome count, endpoint definition, analysis population, and observation-completeness information. The registry record identifies a 6-week timeframe and the intended population, yet does not report the DLT result or the operational rules needed to reconstruct it.
The non-randomized design also matters statistically. Different dose-level groups do not automatically provide a fair comparison of regimens. Without random assignment, observed group differences can reflect participant composition or other factors as well as dose. Clear reporting of allocation, timing, and analysis methods would be needed to judge how much such factors may affect a comparison; these details are not reported in the registry record.
The safety data further demonstrate why event counts, percentages, and endpoint definitions should be kept distinct. Serious adverse events and deaths are important recorded outcomes, but they are not interchangeable with DLTs. Percentages without reported denominators and group attribution cannot establish comparative risks, and event listings do not establish causation.
Finally, the record lists a disease-response outcome but no results or analyses. This distinction between registered outcomes and posted findings is essential: an outcome's presence in a study record does not mean that its value or uncertainty is available. For clinical researchers and statisticians, transparent outcome reporting and analysis methods are necessary for assessing both the information a pilot study contributes and the limits of its conclusions.
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 central limitation for interpretation is that the registry record does not report the primary DLT count, despite specifying the 6-week timeframe. It also does not report the secondary disease response result or any statistical analyses. No estimate of outcome frequency, uncertainty, or association between dose level and outcome can therefore be evaluated.
The study is non-randomized, has no masking, and is described as single-group. Although the record lists Initial and Modified Dose Levels, it does not describe allocation procedures or establish a randomized comparison. The reason for modifying the dose and the reason for termination are not reported in the registry record. Enrollment is listed as 23, but the record does not state how many participants were evaluable for each outcome.
Details needed to interpret the safety information are also absent. The registry record does not report the denominators or dose-level attribution for the selected serious-event percentages, event timing, relationship to treatment, or causes of death. It does not explain how serious adverse events relate to the DLT criteria. Missing-data rules, analysis populations, multiplicity handling, and the statistical analysis plan are not reported.
These limitations are specific to the information available in the registry record. They do not establish that an outcome was absent or that an analysis was not conducted outside the record; they mean that the relevant result and methods are not reported in the registry record. Conclusions should remain limited to the registered design and the safety entries that are explicitly listed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL — NCT01483690.
- Registry record last updated 2020-10-27; status last verified 2020-10.
- Results first posted 2020-10-27.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a Phase 1 and Phase 2 pilot study of decitabine and vorinostat with chemotherapy for pediatric relapsed ALL. The design is non-randomized, unmasked, and single-group, with Initial and Modified Dose Levels. Enrollment is listed as 23, and the status is terminated.
The primary endpoint is the number of participants experiencing DLT over 6 weeks. A disease response rate is listed as a secondary outcome. Neither outcome result nor a statistical analysis is reported in the registry record. Serious adverse-event summaries list 5 participants at risk and affected at the Initial Dose Level and 18 at risk and affected at the Modified Dose Level; death counts are 5 and 13. The record does not report the DLT definition, analysis populations, missing-data approach, or reason for termination.