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 Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia (NCT01056523), a na phase 1, phase 2 study. The primary outcome is Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01056523 |
| Phase | Phase 1, Phase 2 |
| Condition | Acute Myeloid Leukemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Jewish General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with acute myeloid leukemia (AML). The official title identifies AML M4 and M5 subtypes and AML with high eIF4E expression; the registry condition is listed as AML.
Intervention
Ribavirin in combination with low-dose cytarabine arabinoside (Ara-C). Ribavirin was described as oral, twice daily, with dose escalation; Ara-C was described as subcutaneous, twice daily, at 20 mg on days 1 to 10 of a 28-day cycle.
Comparator
There was no separate comparator arm. The study is recorded as a single-group trial with allocation listed as not applicable.
Primary question
What recommended phase II dose of ribavirin should be selected with low-dose Ara-C, considering pharmacokinetics and maximum tolerated dose?
This is a dose-selection question rather than a randomized comparison of treatment strategies. The stated selection criteria required a target steady-state ribavirin level of 20 uM for all patients and allowed no more than 1 of 6 patients at the selected dose to have a dose-limiting toxicity. The primary endpoint timeframe is 56 days.
The registry also lists overall response rate, complete response rate, partial response, and blast response as secondary outcomes. Those outcomes address activity, but no numerical results for them are reported in the registry record. The central question that can be described from the record is therefore how the combination was intended to be evaluated for dose selection, not whether it produced a particular response or clinical benefit.
3. Trial Design
The study is recorded as phase I/II and completed, with 29 participants enrolled. Its start is listed as 2010-01 and its primary completion as 2015-01. Jewish General Hospital is listed as the sponsor. The study condition is acute myeloid leukemia, and the official title specifies AML M4 and M5 subtypes and AML with high eIF4E expression.
The design is single-group, with allocation listed as not applicable and masking listed as none. The registry describes one ribavirin–cytarabine arabinoside arm. Ribavirin was given orally twice daily according to a dose-escalation scheme, daily for 28 days of a 28-day cycle. Cytarabine arabinoside was described as 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle.
The primary objective was to determine the recommended phase II dose of ribavirin with low-dose Ara-C, based on pharmacokinetics and maximum tolerated dose. The registry describes the design as 3+3 and states the dose-selection criteria, but does not report the detailed escalation protocol or the actual dose selected. A protocol-specific sample-size justification is not reported in the registry record.
Because there is no separate control group, the design does not support a like-for-like comparison with another treatment. The enrolled count also does not, by itself, establish how many participants contributed to each outcome analysis. Analysis populations and outcome-specific denominators 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.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 | Dose Level 6 |
|---|---|---|---|---|---|---|
| STARTED | 4 | 3 | 5 | 6 | 3 | 3 |
| COMPLETED | 3 | 3 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 1 | 0 | 2 | 3 | 0 | 0 |
Reasons for not completing this period:
| Reason | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 | Dose Level 6 |
|---|---|---|---|---|---|---|
| Death | 1 | 0 | 2 | 3 | 0 | 0 |
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 | Ribavirin and Cytarabine |
|---|---|---|
| Participants analysed | 29 | |
| Age, Continuous | years | 65 (22 to 83) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 15 |
| FAB subtype: FAB sutype M4/M5 | Participants | 22 |
| FAB subtype: Other FAB subtypes | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C, measured over 56 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the recommended phase II dose of ribavirin when given with low-dose Ara-C. It is expressed in milligrams and has a stated timeframe of 56 days. Rather than measuring a treatment effect against a comparator, this endpoint is intended to identify a dose for subsequent study using both pharmacokinetic information and tolerability.
The registry describes a target steady-state ribavirin level of 20 uM for all patients and a maximum tolerated dose criterion: no more than 1 of 6 patients at the selected dose could have had a dose-limiting toxicity. These are stated selection rules, not reported findings. The record does not give the observed pharmacokinetic values, the number of dose-limiting toxicities at each dose, or the numerical recommended phase II dose.
In general, dose-finding endpoints are used to guide selection of a dose for further evaluation, rather than to establish comparative efficacy. That distinction matters when interpreting a recommended dose: it is a decision based on specified evidence and criteria, not a direct estimate of how much better one treatment is than another. The registry record does not report the endpoint result itself.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes the purpose and decision criteria for a dose-finding study, but does not report a numerical value for the primary endpoint. It therefore does not establish which ribavirin dose was recommended for phase II, how the pharmacokinetic target was met, or how many dose-limiting toxicities occurred at any dose. The stated criteria—steady-state ribavirin 20 uM for all patients and no more than 1 of 6 patients with dose-limiting toxicity at the selected dose—should be read as rules for selection, not as proof that those rules were satisfied.
The enrollment count is 29. That is a study-level count and does not tell readers how many participants contributed to the primary endpoint or to each secondary outcome. The record lists overall response rate, complete response rate, partial response, and blast response, but gives no numerical findings for these outcomes. No treatment-effect estimate, confidence interval, or hypothesis test result is reported in the registry record.
Safety information is reported as counts. Serious adverse events affected 7 of 29 participants at risk, and other adverse events affected 29 of 29 participants at risk. The registry lists syncope, exacerbation of bone pain, cerebrovascular hemorrhage, retinal hemorrhage, visceral shingles, and lower gastro-intestinal hemorrhage as serious adverse event terms, each with a reported percentage of 3.4%. These entries describe reported safety information; they do not establish that the study treatment caused each event. The number of deaths is not reported in the registry record.
For general interpretation, a confidence interval describes the range of values compatible with an estimate under a statistical model. Without a reported estimate and interval, the precision of an effect or dose-related estimate cannot be assessed from this record. Similarly, without a comparator, response observations would not by themselves separate treatment effects from other explanations. No numerical response findings are available to interpret in any case.
The study’s single-group structure is suited to asking a dose-selection question as described in the registry, but it does not provide a randomized control comparison. The registry status is completed, but completion status is not a substitute for posted outcome results. Conclusions should remain limited to the design, criteria, enrollment, and safety counts that the record reports.
9. Statistical Methods Explained
The primary statistical task described in the registry is dose selection. It is not a conventional comparison of two groups. The record identifies a 3+3 design and says the recommended phase II dose was to be based on pharmacokinetics and maximum tolerated dose. It also states criteria involving a target steady-state level and dose-limiting toxicity. The detailed protocol for assigning doses, defining dose-limiting toxicity, or handling incomplete observations is not reported in the registry record.
What does a dose-finding design do?
As a general statistical concept, an early dose-finding study evaluates dose levels to inform which dose should be studied further. Tolerability information is considered alongside evidence that the drug reaches a relevant exposure. A design of this kind answers a different question from a trial designed to estimate a comparative treatment effect. The aim is to make a dose-selection decision under stated rules, not to establish that one regimen is superior to a control.
The registry’s specific rule called for a steady-state ribavirin level of 20 uM for all patients and no more than 1 of 6 patients with a dose-limiting toxicity at the selected dose. Those criteria identify what the record says was required for selecting a dose. The actual pharmacokinetic observations, dose-specific toxicity counts, and selected dose are not reported. Without them, readers cannot reproduce the dose-selection decision or evaluate how closely observed data matched the criteria.
Why combine pharmacokinetics and tolerability?
In general, pharmacokinetics describes drug exposure in the body, while tolerability describes adverse effects that can limit a dose. Considering both can help distinguish a dose that achieves a target exposure from one whose adverse effects make further use difficult. This is a general explanation of the concepts, not a report of findings in this study. The registry identifies pharmacokinetics and maximum tolerated dose as the basis for selection, but does not give exposure summaries or dose-specific toxicity results.
A maximum tolerated dose is a dose-selection concept tied to observed toxicity under a protocol’s definitions and observation rules. The record does not provide those definitions or specify the full monitoring procedures. The 56-day timeframe is listed for the primary endpoint, but the registry does not explain how that timeframe was applied to each participant or how observations outside it were handled.
What can a single-group design estimate?
In general, a single-group study can describe outcomes among participants receiving the study regimen. It cannot directly estimate a randomized between-group contrast when no comparator arm exists. A response count in a single group may be informative descriptively, but it is not by itself a controlled estimate of what would have happened under another treatment. Here, the registry does not report numerical response findings, so even descriptive response interpretation is limited.
Allocation is listed as not applicable, masking as none, and the model as single group. These design features mean that a comparison with an assigned control group is not part of the registry description. No claim about the direction or size of a comparative effect can be derived from the enrollment count or the stated study objective.
What do counts and denominators mean?
A count is interpretable only in relation to the group and denominator to which it applies. The safety record lists 29 participants at risk for serious adverse events and 7 affected; for other adverse events, it lists 29 at risk and 29 affected. These are registry safety counts. They should not be confused with the number of participants who completed treatment, met an analysis definition, or contributed to a particular efficacy outcome. Those outcome-specific populations are not reported in the registry record.
In general, a denominator can differ across outcomes if observations are unavailable or if eligibility for an analysis differs. The registry does not state whether missing outcome data occurred, how such data were handled, or whether every enrolled participant was included in each analysis. It would therefore be inappropriate to assume a particular analysis population from enrollment alone.
What is not available for statistical assessment?
The record lists five outcome measures and zero analyses. It does not report numerical primary or secondary outcome results, confidence intervals, p-values, or a statistical analysis plan. Without an estimate and its uncertainty, precision cannot be assessed. Without an analysis plan, it is not possible to determine from the registry whether analyses were prespecified, adjusted, or exploratory.
In general, over-dispersion occurs when observed variability exceeds what a model assumes; ignoring it can make uncertainty estimates too small. That issue cannot be assessed from the registry information because no outcome model or relevant outcome data are reported. Likewise, no recalculated comparison is described in the record, and there is no posted effect estimate to evaluate against a sponsor analysis.
Planning calculations are distinct from observed trial outcomes. A planning illustration based on an assumed effect is not an observed result or observed power. The registry does not report the protocol’s sample-size justification, and it does not report a numerical primary endpoint result from which readers could evaluate a study-specific dose-selection estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four secondary outcomes: overall response rate, complete response rate, partial response, and blast response. It lists five outcome measures in total. No numerical results or analyses are reported for these outcomes in the registry record, so there are no posted estimates from which to assess their precision or compare their findings.
In general, multiplicity arises when several outcomes or statistical tests are considered. If multiple tests are used to make confirmatory claims, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. Whether or how multiplicity was handled in this study is not reported in the registry record. No adjustment method or hierarchy among the listed outcomes is described.
The registry reports 29 participants enrolled, but does not give outcome-specific analysis populations or denominators. Enrollment should not be treated as proof that all participants were included in every outcome analysis. The numbers of participants with evaluable pharmacokinetic data, dose-limiting toxicity assessments, or response assessments are not reported in the registry record.
Missing-data procedures are also not reported. The record does not say whether any data were missing, why data might have been unavailable, or whether any imputation or sensitivity analysis was planned. In general, missingness can affect an estimate when the people with observed data differ systematically from those without them; conclusions depend on the missing-data assumptions and methods. No such assumptions can be evaluated from the registry information.
The analysis populations, statistical analysis plan, and handling of missing observations are not reported in the registry record. These absences limit assessment of how the listed outcomes would have been analyzed, even apart from the lack of posted numerical results.
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 |
|---|---|---|---|
| Ribavirin-Cytarabine | 7 | 29 | 24.1% |
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 |
|---|---|
| Ribavirin-Cytarabine | 29 of 29 |
Most frequent serious adverse event terms
| Event term | Organ system | Ribavirin-Cytarabine |
|---|---|---|
| Syncope | Nervous system disorders | 1 of 29 |
| Exacerbation of bone pain | Musculoskeletal and connective tissue disorders | 1 of 29 |
| Cerebrovascular hemorrhage | Nervous system disorders | 1 of 29 |
| retinal hemorrhage | Eye disorders | 1 of 29 |
| visceral shingles | Infections and infestations | 1 of 29 |
| Lower gastro-intestinal hemorrhage | Gastrointestinal disorders | 1 of 29 |
| Sepsis | Infections and infestations | 1 of 29 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ribavirin-Cytarabine |
|---|---|---|
| anemia | Blood and lymphatic system disorders | 15 of 29 |
| febrile neutropenia | Blood and lymphatic system disorders | 13 of 29 |
| mucositis | Gastrointestinal disorders | 12 of 29 |
| fatigue | General disorders | 12 of 29 |
| infection | Infections and infestations | 8 of 29 |
| nausea | Gastrointestinal disorders | 7 of 29 |
| thrombocytopenia | Blood and lymphatic system disorders | 7 of 29 |
| vomiting | Gastrointestinal disorders | 6 of 29 |
| fever | General disorders | 6 of 29 |
| musculoskeletal pain | Musculoskeletal and connective tissue disorders | 6 of 29 |
Serious events with the highest arm-level rate: syncope (3.4%), exacerbation of bone pain (3.4%), cerebrovascular hemorrhage (3.4%), retinal hemorrhage (3.4%), visceral shingles (3.4%).
The safety record lists 29 participants at risk for serious adverse events, of whom 7 were affected. For other adverse events, it lists 29 at risk and 29 affected. These figures describe the registry’s reported counts; they do not identify the number of separate events or show that every event was caused by the study treatment.
The serious adverse event terms listed are syncope, exacerbation of bone pain, cerebrovascular hemorrhage, retinal hemorrhage, visceral shingles, and lower gastro-intestinal hemorrhage. Each term is accompanied by a reported percentage of 3.4%. The record does not give further event-level detail, such as timing, severity grades, recurrence, or participant-level overlap among terms.
Serious adverse events and other adverse events are separate registry categories. The number of deaths is not reported in the registry record; a null entry should not be interpreted as evidence that no deaths occurred. In general, safety counts describe events observed and recorded under a study’s procedures. They do not, without an appropriate comparison and further assessment, establish causality or quantify comparative risk.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed phase I/II, single-group study enrolled 29 participants and was designed to select a recommended phase II dose of ribavirin with low-dose Ara-C. It states the dose-selection criteria and regimen description, and it reports safety counts. It does not report the numerical recommended dose, pharmacokinetic findings, dose-limiting toxicity counts by dose, or numerical response results.
Accordingly, the record does not support a conclusion about the size or precision of a treatment effect. It contains no randomized control comparison and no reported response estimates or confidence intervals. The listed secondary outcomes indicate what was of interest, not what the study found. Likewise, a completed status does not supply missing outcome values.
In general, a dose-selection result can inform the choice of a regimen for subsequent evaluation, but it is not equivalent to evidence from a controlled trial of comparative benefit. Safety counts can describe reported events in the enrolled group, but they do not alone establish that the regimen caused those events or how its safety compares with an alternative.
The registry’s figures should therefore be interpreted narrowly: 7 of 29 participants at risk were reported as affected by serious adverse events, and 29 of 29 at risk were reported as affected by other adverse events. The listed serious-event terms each carry a reported 3.4% value. The record does not provide enough detail to infer participant overlap across terms, event timing, or causality.
What the record does not mean is that the dose-selection criteria were met, that a particular dose was selected, or that the regimen produced a specific response. Those outcomes are not reported in the registry record. The statistical interpretation is limited to the stated design, intended endpoint, criteria, and posted safety counts.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary question is dose selection rather than a comparison between treatment groups. That distinction changes what counts as a useful result: the registry describes a decision based on pharmacokinetics and maximum tolerated dose, with explicit criteria for steady-state exposure and dose-limiting toxicity. A dose-finding objective should not be interpreted as though it were a randomized efficacy comparison.
The design also illustrates why an endpoint definition and an endpoint result are different things. The registry specifies the recommended phase II dose in milligrams as the primary endpoint and gives a 56-day timeframe, but does not report the selected dose. A clearly stated decision rule can make the intended analysis understandable; it cannot substitute for the data needed to see how the rule was applied.
Another important statistical issue is the boundary between enrollment and analysis. The record lists 29 participants enrolled and safety denominators of 29, but does not report outcome-specific analysis populations. This prevents readers from assuming that the same participants contributed to every measure. Reporting clear denominators is essential for interpreting both estimates and safety counts.
Finally, the single-group design limits comparative interpretation. It can provide information within the treated group, but cannot make a randomized contrast with an unobserved control group. The record’s missing numerical primary and secondary results further constrain what can be concluded. These features make careful separation of study purpose, design, reported observations, and absent findings especially important.
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 registry record does not report a numerical recommended phase II dose, the observed pharmacokinetic results, or the dose-limiting toxicity counts by dose. The stated 20 uM target and the criterion of no more than 1 of 6 patients with dose-limiting toxicity describe the intended selection rule, not whether it was achieved. The actual dose-selection decision cannot be checked from the record.
Numerical results for the listed secondary outcomes are also not reported. The record lists overall response rate, complete response rate, partial response, and blast response, but provides no estimates or outcome-specific denominators. No confidence intervals, p-values, or statistical analysis details are reported, limiting assessment of uncertainty and analytic choices.
The single-group design has no comparator arm, so it cannot provide a randomized between-group contrast. Masking is listed as none. The registry does not report a protocol-specific sample-size justification, detailed dose escalation procedures, definitions of dose-limiting toxicity, or the analysis populations.
Missing-data methods and multiplicity handling are not reported in the registry record. Safety entries also lack detail about event timing, severity grades, participant overlap among terms, and causal attribution. The death count is not reported in the registry record. These limitations mean that the posted information supports description of the study plan and selected safety counts, but not a complete assessment of the primary dose-selection result or comparative outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia — NCT01056523.
- Registry record last updated 2023-10-02; status last verified 2023-09.
- Results first posted 2017-01-30.
- 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.
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18. Record Summary
The registry describes a completed phase I/II, single-group study of ribavirin with low-dose cytarabine arabinoside in acute myeloid leukemia. It lists 29 participants enrolled and identifies AML M4 and M5 subtypes and AML with high eIF4E expression in the official title. Ribavirin was described as oral, twice daily, with dose escalation; cytarabine arabinoside was described as 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle.
The primary endpoint was the recommended phase II dose of ribavirin, based on pharmacokinetics and maximum tolerated dose, with a 56-day timeframe. The stated criteria included a 20 uM steady-state target and no more than 1 of 6 patients with dose-limiting toxicity at the selected dose. The numerical dose result and secondary outcome results are not reported in the registry record.
Safety counts list 7 of 29 participants affected by serious adverse events and 29 of 29 affected by other adverse events. No death count is reported in the registry record.