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 Lenalidomide and AT-101 in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia (NCT01003769), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01003769 |
| Phase | Phase 1, Phase 2 |
| Condition | Recurrent Chronic Lymphocytic Leukemia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
Patients with relapsed B-cell chronic lymphocytic leukemia (B-CLL) were the intended population. The registry describes the condition as recurrent chronic lymphocytic leukemia. The record reports enrollment of 5 and says the trial terminated early with too few patients to analyze its primary endpoint. It does not report detailed participant characteristics or how closely the enrolled group represented the broader population with relapsed B-CLL.
Intervention
The study evaluated lenalidomide in combination with AT-101, also identified in the intervention list as R-(-)-gossypol acetic acid. The treatment description specifies lenalidomide by mouth once daily on days 1–21. Beginning in course 2, patients also receive AT-101 by mouth twice daily on days 1–3. The regimen repeats every 28 days for up to 11 courses, with a longer stated duration for course 12 or the last course. The record does not establish that every participant received the full planned schedule.
Comparator
There was no separate control group. The trial is registered as a single-group study, and allocation is listed as not applicable. Consequently, the treatment group cannot be compared with a randomized control group within this trial. Any comparison with outcomes from other populations or studies would require information not reported in the registry record and would not have the protection against confounding that randomization provides.
Primary question
The primary question was how to identify the maximum tolerated dose of lenalidomide when combined with AT-101. The endpoint was defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients, described as at least 2 of a maximum of 6 new patients. The endpoint timeframe was up to day 28 of course 2. The registry says the study ended early with too few patients to analyze this endpoint, so it does not report a maximum tolerated dose from the trial.
The record also lists secondary questions about adverse events and toxicity during phase I, and overall response rate, time to progression, and adverse events during phase II. These outcomes could describe tolerability and disease outcomes, but the registry record does not report analyses for them. The study therefore does not provide a usable estimate of comparative treatment effects. Its design and the limited posted results support a description of the trial’s aims and recorded safety counts, not a conclusion about whether the regimen changes clinical outcomes.
3. Trial Design
This was a phase I/II, single-group clinical trial of lenalidomide combined with AT-101 in patients with relapsed B-CLL. The registry lists allocation as not applicable and masking as none. There was no randomized comparison group, so the study was not designed to estimate a treatment effect relative to a concurrent control. Enrollment is reported as 5. The record’s status is terminated, and it states that too few patients were available to analyze the primary endpoint.
The regimen description specifies lenalidomide by mouth once daily on days 1–21. Starting in course 2, AT-101 was added by mouth twice daily on days 1–3. Courses were intended to repeat every 28 days for up to 11 courses; course 12 or the last course was described as lasting 49–56 days. Treatment was to continue in the absence of disease progression or unacceptable toxicity. These details describe the planned administration, not proof that each enrolled patient completed each course or received every planned dose.
The phase I primary outcome was maximum tolerated dose, assessed up to day 28 of course 2. Its definition relies on identifying dose-limiting toxicity at dose levels, but the record says the number of patients was too small to analyze that endpoint. Secondary outcomes include phase I adverse events and toxicity, followed by phase II overall response rate, time to progression, and adverse events. The registry lists 7 outcome measures and no analysis entries.
The record does not report a statistical analysis plan, a sample-size justification, interim analyses, or a detailed account of the reasons for termination. It also does not report a control-group strategy because the trial is single-group. The absence of these details limits assessment of how the investigators intended to summarize outcomes beyond the endpoint definitions and treatment description in the registry.
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 | Dose Level 1 (Lenalidomide in Combination With AT-101) |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Trial terminated early with too few patients to analyze this endpoint.
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: All patients registered to Dose Level 1 are included in this analysis.
| Characteristic | Unit | Dose Level 1 (Lenalidomide in Combination With AT-101) |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 61 (50 to 72) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose, measured over Up to day 28 of course 2.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was maximum tolerated dose of lenalidomide given with AT-101. The registry defines it as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients, stated as at least 2 of a maximum of 6 new patients. The assessment period was up to day 28 of course 2.
In general, a maximum-tolerated-dose endpoint is used in early-phase research to characterize a dose-limiting toxicity boundary for a treatment regimen. It focuses on tolerability under the study’s dose-escalation approach; it is not itself a measure of comparative efficacy. The endpoint definition links the conclusion to observed toxicity at particular dose levels and to how many patients are evaluated at those levels. With small groups, a limited number of events can strongly affect whether a threshold appears to have been reached, so the estimate is inherently dependent on the observed data and the escalation procedure.
For this trial, the registry explicitly says that it terminated early with too few patients to analyze the primary endpoint. It therefore does not report a maximum tolerated dose. Nor does the record give a dose-by-dose account of participants evaluated or dose-limiting toxicities that would support an independent reconstruction. The endpoint’s intended role can be described, but no dose recommendation or toxicity threshold can be inferred from the posted primary-outcome result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key statistical fact is that the primary endpoint was not analyzed. The registry states that the trial terminated early with too few patients to analyze maximum tolerated dose. This means the central phase I question remains unanswered in the posted record. The endpoint definition is available, but a definition is not an estimate: the registry does not report a selected dose level, a dose-limiting-toxicity summary by dose, or an uncertainty interval for the maximum tolerated dose.
The trial enrolled 5 and used a single-group design without masking. Because there is no randomized comparator, the study cannot separate changes associated with treatment from the natural course of disease, patient selection, or other influences. This is a design limitation for causal comparisons, not evidence that the regimen has or lacks an effect. The registry’s status is terminated, but the specific reason for termination beyond the stated inability to analyze the primary endpoint is not reported in the registry record.
There are limited posted safety counts. In the listed dose-level group, 2 of 5 were affected by serious adverse events, and 5 of 5 were affected by other adverse events; the listed number of deaths is 0. The record also lists fatigue, lung infection, and maculo-papular rash among the leading serious-event terms, each at 20.0%. These figures are descriptive. The record does not supply an inferential comparison, a confidence interval, or a complete time-at-risk description for interpreting them as rates over a defined follow-up period.
The registry lists phase II outcomes including overall response rate and time to progression, but no analyses are posted. As a result, the record does not provide an estimate of response or progression timing, and no precision assessment is possible for those outcomes. A missing analysis is not a result showing no response, no progression, or no treatment effect; it means those quantities are not reported in the registry record.
Overall, the posted information supports a narrow interpretation: the trial was intended to study dose and toxicity, but it ended with too few patients for analysis of its primary endpoint. The safety figures describe the listed group, while efficacy outcomes remain unreported. They cannot establish benefit, harm relative to another treatment, or the balance of benefits and risks for patients with relapsed B-CLL.
9. Statistical Methods Explained
The registry identifies this study as phase I/II and single-group. Those design features shape what can be learned from its data. Phase I work commonly focuses on dose and tolerability, while later-phase work may assess outcomes such as response or time to progression. That general distinction helps explain why this record has both a maximum-tolerated-dose primary endpoint and listed phase II outcomes. It does not establish which analyses were completed: the registry reports no analysis entries.
What does a maximum tolerated dose mean?
In general, a maximum-tolerated-dose analysis uses observed dose-limiting toxicities to identify a dose level considered tolerable under the study’s specified rules. The registry defines the endpoint as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients, with the threshold described as at least 2 of a maximum of 6 new patients. The timeframe is up to day 28 of course 2. This is a threshold-based dose-finding question, not a comparison of outcomes between treatment groups.
The result depends on which dose levels were evaluated, how many patients were assessed at each level, and the toxicity outcomes observed. In general, when the number of observations is limited, the estimate can be sensitive to a small number of events. The registry does not report dose-level assignments or dose-limiting-toxicity counts sufficient to reconstruct the analysis. It instead states that too few patients were available to analyze the primary endpoint. Thus, the stated rule can be explained, but it cannot be applied to produce a trial-specific dose estimate from the posted results.
What does the single-group design permit?
In general, a single-group study can describe outcomes among people receiving a regimen, but it lacks a concurrent comparison group for estimating what would have happened under another treatment or under no study treatment. Here, allocation is listed as not applicable, masking as none, and the model as single group. The recorded safety counts can therefore be read descriptively for the listed group. They are not a randomized comparison, and they do not by themselves estimate treatment-attributable risk or comparative efficacy.
Masking refers generally to keeping treatment or outcome information concealed from participants, investigators, or assessors, depending on the design. The registry lists no masking. That information describes the study design; it does not, on its own, establish whether any particular outcome assessment was biased. The registry record does not provide further details about outcome-assessment procedures or safeguards.
How should adverse-event counts be read?
Adverse-event counts describe events recorded under the study’s definitions and observation procedures. The record lists 5 at risk for serious adverse events, with 2 affected, and 5 at risk for other adverse events, with 5 affected. It lists 0 deaths. The serious-event terms include fatigue, lung infection, and maculo-papular rash, each reported at 20.0%. These entries should be kept distinct: affected participants, event terms, and event totals are not interchangeable measures. A person may experience more than one event, and the registry does not state whether the listed terms overlap within participants.
In general, a percentage for an event term describes the reported frequency under the registry’s reporting conventions; it does not convey how long participants were observed or whether the event was caused by treatment. The record does not report the adverse-event observation period, event dates, or a detailed attribution breakdown for the serious-event summary. The listed secondary outcomes refer to grading and, for one phase I toxicity outcome, treatment-relatedness categories, but the posted group summary does not provide a full account of those classifications.
Why do uncertainty intervals and tests matter?
In general, an estimate describes the observed value of an outcome, while a confidence interval conveys its statistical uncertainty under a stated method. A hypothesis test addresses compatibility of data with a specified null hypothesis and model assumptions. Neither can be meaningfully interpreted without the relevant estimate, analysis population, and method. The registry does not report estimates, confidence intervals, or p-values for the primary endpoint or the phase II efficacy outcomes. It is therefore not possible to assess precision or statistical evidence for those outcomes from the posted record.
Small studies usually yield less precise estimates than larger studies, all else equal, because they contain less information. This general principle is especially relevant to dose finding, where conclusions may depend on a limited number of toxicity observations. It does not allow a numerical uncertainty calculation in this case: the necessary endpoint data and analyses are not reported in the registry record. The stated enrollment alone cannot substitute for outcome counts or an analysis.
What about over-dispersion and repeated outcomes?
In general, over-dispersion occurs when variability in observed counts is greater than a statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for the extra variability. This concept may matter for count outcomes or clustered observations, but the registry does not report a model for the listed outcomes, nor does it provide data that establish over-dispersion in this trial. It would be inappropriate to assert that over-dispersion occurred or to assign a particular model to the investigators.
Repeated measurements and time-to-event outcomes also require methods that account for their structure. Time to progression, listed as a phase II outcome, generally concerns elapsed time until an event, with methods that may account for participants whose event time is not observed during follow-up. The registry does not report a time-to-progression analysis, follow-up distribution, censoring details, or an analysis method. No survival estimate or comparison can therefore be interpreted from this record.
The record’s sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect framed as a fraction of an observed effect. These are planning assumptions, not evidence that the trial itself used that design: the actual study is registered as single-group. Sample-size illustrations are not observed power and cannot replace analysis of trial outcomes. The registry does not report a statistical analysis plan, a sample-size justification for the actual study, or interim analyses.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures, including the primary maximum-tolerated-dose endpoint and secondary safety and efficacy outcomes. It does not report analysis entries. The record does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for deciding which secondary analyses would be considered confirmatory. These details are not reported in the registry record.
In general, testing multiple outcomes can increase the chance of finding at least one apparently unusual result even when none represents a true effect. Statistical plans may address this by prioritizing outcomes, adjusting significance thresholds, or treating secondary analyses as exploratory. Without the study’s analysis plan and outcome results, there is no basis to determine whether multiplicity was addressed or how it would affect interpretation. No claim about adjusted or unadjusted significance is possible from the posted record.
Missing outcome information also limits interpretation. The registry says too few patients were available to analyze the primary endpoint, but it does not provide participant-level outcome data, reasons for missing observations, or analysis populations for the listed secondary outcomes. It does not report how many participants contributed data to any particular efficacy analysis. The record therefore cannot establish whether missingness was related to treatment, prognosis, follow-up, or another factor.
In general, missing data can affect estimates when the probability of an outcome being unobserved is related to the outcome itself or to factors associated with it. Assessing that possibility requires information about who was assessed, when, and why observations were unavailable, together with the planned analysis approach. Those details are not reported in the registry record. The appropriate reading is that the primary endpoint could not be analyzed and that analyses of the listed secondary outcomes are not posted—not that missing outcomes should be treated as favorable, unfavorable, or equal to a particular value.
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 |
|---|---|---|---|
| Dose Level 1 (Lenalidomide in Combination With AT-101) | 2 | 5 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Level 1 (Lenalidomide in Combination With AT-101) | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Level 1 (Lenalidomide in Combination With AT-101) | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Level 1 (Lenalidomide in Combination With AT-101) |
|---|---|---|
| Fatigue | General disorders | 1 of 5 |
| Lung infection | Infections and infestations | 1 of 5 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Level 1 (Lenalidomide in Combination With AT-101) |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 5 of 5 |
| Neutrophil count decreased | Investigations | 5 of 5 |
| Platelet count decreased | Investigations | 5 of 5 |
| Constipation | Gastrointestinal disorders | 3 of 5 |
| Fatigue | General disorders | 1 of 5 |
| Upper respiratory infection | Infections and infestations | 1 of 5 |
| Alanine aminotransferase increased | Investigations | 1 of 5 |
| Aspartate aminotransferase increased | Investigations | 1 of 5 |
| Blood bilirubin increased | Investigations | 1 of 5 |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 5 |
Serious events with the highest arm-level rate: fatigue (20.0%), lung infection (20.0%), rash maculo-papular (20.0%).
The listed dose-level group reports 5 at risk for serious adverse events and 2 affected. For other adverse events, 5 were at risk and 5 were affected. The record lists 0 deaths. It also identifies fatigue, lung infection, and maculo-papular rash as leading serious-event terms, each reported at 20.0%.
These are descriptive safety figures for the registry’s listed group, not a comparison with a control group. The record does not report the observation period for these counts, a full participant-level event history, or enough detail to determine whether a person could contribute to more than one listed term. The percentages attached to serious-event terms should not be added together or treated as mutually exclusive categories. Nor do the counts alone show that an event was caused by treatment.
Secondary-outcome descriptions refer to adverse-event grading and toxicity classifications, including treatment-relatedness categories for a phase I outcome. The posted summary does not give a full grading or attribution breakdown alongside the group counts. These figures should therefore be read as the recorded safety summary, with substantial limits on duration, attribution, and comparative interpretation.
12. What the Result Does, and Does Not, Mean
The registry record establishes what the study set out to investigate: a lenalidomide and AT-101 regimen for relapsed B-CLL, with maximum tolerated dose as the primary endpoint and several safety and phase II outcomes listed as secondary outcomes. It also records enrollment of 5, a single-group design, and terminated status. These registry entries characterize the study but do not establish the regimen’s clinical effect.
The primary dose-finding question cannot be answered from the posted results because the registry says too few patients were available to analyze maximum tolerated dose. No dose estimate is reported. The efficacy outcomes, including overall response rate and time to progression, are listed but have no posted analyses. It would be incorrect to interpret an absent analysis as evidence that no responses occurred or that progression was unchanged.
The adverse-event entries offer limited descriptive information: 2 of 5 were affected by serious adverse events, 5 of 5 by other adverse events, and 0 deaths are listed. The record does not provide enough context to determine event duration, attribution, or comparative risk. These counts neither establish causation nor provide a controlled estimate of safety.
More generally, statistical interpretation depends on the design, completeness of observations, analysis methods, and uncertainty around estimates. Here, the lack of a control group prevents a randomized comparison, while the limited enrollment and unavailable endpoint analysis prevent a trial-specific estimate of the primary dose outcome. The registry does not report confidence intervals or hypothesis tests for efficacy outcomes. The result is not evidence for or against treatment effectiveness; it is an incomplete record of a trial whose intended primary analysis could not be conducted.
The study may still be relevant as a record of a proposed combination regimen and its intended dose-finding question. However, no treatment recommendation or conclusion about benefit or harm relative to other care follows from these data. The registry does not report the reasons for termination beyond the statement that too few patients were available to analyze the primary endpoint.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it illustrates the gap between a clearly defined endpoint and an endpoint that can actually be estimated. The registry specifies a maximum-tolerated-dose rule and a timeframe, but also states that too few patients were available to analyze it. A precise definition does not overcome a lack of usable observations. Without the dose-level outcomes and analysis, the intended primary question remains unresolved.
The single-group design is also important. A treatment group without a concurrent randomized comparator can support descriptive reporting, but it cannot distinguish treatment-related changes from other explanations as reliably as a randomized comparison. This distinction matters particularly when a registry lists both safety and efficacy aims: the presence of an outcome in the study plan does not mean that the design or posted results can establish a causal treatment effect.
The safety summary further demonstrates why counts need context. The record reports affected participants and leading serious-event terms, but does not state the observation period or provide a detailed attribution analysis alongside those figures. Counts are useful for describing what was recorded, yet they cannot alone express comparative risk or establish causation.
Finally, the record lists phase II outcomes without posting their analyses. Separating an outcome’s planned role from its reported result is essential for readers. An unreported estimate has no assessable precision, and an absent analysis is not a null finding. The study’s most defensible statistical interpretation is therefore limited: the trial intended to evaluate dose and safety, but the primary endpoint was not analyzed and comparative efficacy is not established by the posted record.
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 trial-specific limitation is that the registry reports too few patients to analyze the primary maximum-tolerated-dose endpoint. Although enrollment is listed as 5, the record does not provide the dose-level distribution or toxicity observations needed to reconstruct that analysis. The maximum tolerated dose is not reported.
The study is single-group, with allocation listed as not applicable and masking listed as none. There is no randomized control group against which to compare safety or efficacy. This restricts causal interpretation and makes descriptive outcomes vulnerable to influences that a concurrent control could help address. The record does not report the reasons for termination beyond the statement about insufficient numbers for the primary analysis.
The posted safety information is limited. It includes counts for serious and other adverse events, a death count, and leading serious-event terms, but does not report the observation period, participant-level overlap among terms, detailed attribution, or complete grading information with the group summary. The time-to-progression and overall-response outcomes are listed without analyses. Their estimates, precision, and analysis populations are not reported in the registry record.
The registry also does not report a statistical analysis plan, a sample-size justification for the actual single-group trial, interim analyses, or methods for handling missing data and multiple outcomes. These omissions limit assessment of whether analyses followed prespecified methods and how uncertainty would have been handled. The record’s planning assumptions refer to a two-arm illustration, which is not the registered single-group design; no planning illustration can compensate for the unavailable primary analysis or serve as observed evidence about treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lenalidomide and AT-101 in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia — NCT01003769.
- Registry record last updated 2020-06-16; status last verified 2020-06.
- Results first posted 2020-06-16.
- 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
NCT01003769 is a phase I/II, single-group study of lenalidomide in combination with AT-101 for relapsed B-cell chronic lymphocytic leukemia. The registry lists no masking, enrollment of 5, and terminated status. The planned regimen adds AT-101 beginning in course 2.
The primary endpoint was maximum tolerated dose of lenalidomide with AT-101, assessed up to day 28 of course 2. The registry says the trial terminated early with too few patients to analyze that endpoint, and no maximum tolerated dose is reported. Listed secondary outcomes include adverse events, toxicity, overall response rate, and time to progression; the registry reports no analysis entries.
The safety summary lists 2 of 5 affected by serious adverse events, 5 of 5 affected by other adverse events, and 0 deaths. Fatigue, lung infection, and maculo-papular rash are each listed among leading serious-event terms at 20.0%. Without a comparator or fuller outcome analyses, these entries are descriptive and do not establish comparative safety or efficacy.