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 Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (NCT01059786), a randomized phase 2 study. The primary outcome is Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01059786 |
| Phase | Phase 2 |
| Condition | Hairy Cell Leukemia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 69 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Adults with hairy cell leukemia that had not responded well to, or had relapsed after, standard therapies were eligible. The registry record lists an enrollment of 69.
Intervention
One randomized treatment was rituximab with pentostatin. The record also describes earlier, non-randomized tolerability groups receiving rituximab with bendamustine at 70 mg/m^2 or 90 mg/m^2.
Comparator
The randomized comparison was rituximab with pentostatin versus rituximab with bendamustine at the tolerated dose, listed as 90 mg/m^2 in the randomized arm description. The record does not describe a randomized rituximab-alone arm.
Primary question
The primary endpoint counts participants receiving either combination who achieved complete remission or partial response by the end of treatment, approximately 6 months. The registry record does not report the response counts or a comparative statistical estimate.
The study is listed as a Phase II randomized trial with a crossover model and no masking. Its stated objectives include assessing whether either combination is more effective than rituximab alone, as well as comparing pentostatin and bendamustine when combined with rituximab. However, the arm descriptions identify randomized groups receiving the two combination regimens, not a randomized rituximab-alone group. The registry record does not explain how the objective involving rituximab alone was to be addressed.
The crossover model and the secondary outcome title indicate that crossover treatment after failure of the first regimen was of interest. The registry record does not report the detailed crossover sequence, eligibility rules, or timing. Consequently, the primary question is best read as the reported count of responses to the combination treatments, while the precise randomized contrast and the role of later treatment require caution in interpretation.
3. Trial Design
The registry lists this as a randomized Phase II trial of rituximab with pentostatin or bendamustine for multiply relapsed or refractory hairy cell leukemia. Allocation is recorded as randomized, masking as none, and the model as crossover. Enrollment is 69. The study is listed as active, not recruiting, with primary completion on 2022-12-15.
The record describes an initial tolerability stage with non-randomized bendamustine-rituximab groups at 70 mg/m^2 and 90 mg/m^2; both are marked closed. It then describes randomized treatment with bendamustine at the tolerated dose or with pentostatin, each combined with rituximab. A further non-randomized group is described as allowing up to 4 total participants to receive bendamustine and/or pentostatin with rituximab after the tolerability studies. These stages should not be treated as a single randomized comparison: only the specifically identified randomized arms represent the randomized comparison, while the earlier and additional groups have different allocation descriptions.
The brief summary describes four treatment cycles of 28 days each. The primary endpoint is assessed at the end of treatment, approximately 6 months. The record also names secondary outcomes involving response, crossover treatment after failure of the first regimen, thrombocytopenia, disease biology, measurable residual disease, disease-free survival, and overall survival.
The registry describes the trial's structure but does not report the detailed randomization procedure, allocation ratio, crossover rules, or statistical analysis plan. It also does not report a sample-size justification. Without those details, the design can be described at the level of the recorded arms and outcomes, but not reconstructed beyond the registry's account.
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 | Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to Pentostatin-Rituximab | Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab |
|---|---|---|---|---|---|
| STARTED | 6 | 6 | 28 | 28 | 1 |
| COMPLETED | 6 | 6 | 24 | 27 | 1 |
| NOT COMPLETED | 0 | 0 | 4 | 1 | 0 |
Reasons for not completing this period:
| Reason | Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to Pentostatin-Rituximab | Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab |
|---|---|---|---|---|---|
| Did not receive 6 cycles. | 0 | 0 | 4 | 1 | 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 | Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to Pentostatin-Rituximab | Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 28 | 28 | 1 | 69 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 6 | 16 | 15 | 0 | 39 |
| Age, Categorical: >=65 years | Participants | 4 | 0 | 12 | 13 | 1 | 30 |
| Age, Continuous | years | 66.65 (SD 3.03) | 58.67 (SD 3.14) | 61.87 (SD 9.75) | 61.55 (SD 12.23) | 71.2 (SD 0) | 62.01 (SD 10.14) |
| Sex: Female, Male: Female | Participants | 2 | 0 | 6 | 4 | 0 | 12 |
| Sex: Female, Male: Male | Participants | 4 | 6 | 22 | 24 | 1 | 57 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 6 | 28 | 26 | 1 | 67 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 2 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 2 | 1 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 6 | 5 | 26 | 27 | 1 | 65 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 6 | 6 | 28 | 28 | 1 | 69 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR), measured over At end of treatment, approximately 6 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a count of participants receiving pentostatin plus rituximab or bendamustine plus rituximab who achieved complete remission or partial response. The assessment is specified for the end of treatment, approximately 6 months. The registry defines complete remission using blood-cell measures, spleen findings, and evidence of circulating hairy cell leukemia cells, with the criteria sustained for at least 4 weeks. Partial response is defined using improvements in blood counts, a decrease in circulating malignant cells, and reduction in evaluable lymphadenopathy, also sustained for at least 4 weeks.
Combining complete and partial response gives a clinically interpretable summary of participants meeting either response category under the stated criteria. A count is straightforward to understand, but by itself it does not show the response proportion in each treatment group, the uncertainty around those proportions, or the size and precision of a between-group difference. Those interpretations require the relevant group denominators and an analysis. The registry record does not report the primary response counts or a comparative estimate, so the endpoint definition can be described but the observed response cannot be assessed from this record.
General: a prespecified endpoint helps focus a trial on a defined outcome and assessment time. The meaning of the endpoint depends on applying its criteria consistently and reporting how many participants were assessed, how missing assessments were handled, and how the groups were compared. Those analysis details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and the trial arms, but it does not report the numbers of participants achieving complete remission or partial response. It also reports no statistical analyses. Therefore, no treatment-specific response estimate, comparison, confidence interval, or significance test can be interpreted from the record. The absence of those results is not evidence that the treatments had equal outcomes, nor does it establish that one regimen performed better.
The randomized comparison described is between rituximab with bendamustine at the tolerated dose and rituximab with pentostatin. This is distinct from the trial objectives in the brief summary that mention comparison with rituximab alone. No randomized rituximab-alone arm appears in the arm descriptions, and the registry record does not explain how that objective relates to the reported randomized comparison. The record also describes earlier non-randomized tolerability groups. Their participants should not automatically be combined with randomized participants when interpreting a treatment contrast, because the allocation methods differ.
The crossover model introduces another interpretive consideration. The record names a secondary outcome concerning the two combinations in crossover when used after failure of the first regimen. It does not report the sequence-specific results or the rules for entering crossover treatment. Responses after a switch could answer a different question from responses during the randomized first treatment, so those outcomes would need to be presented separately and interpreted in light of the treatment sequence.
The safety record reports serious adverse events in the randomized groups: 8 of 28 participants in the bendamustine-rituximab group and 7 of 28 in the pentostatin-rituximab group. It also lists deaths in these groups, without providing a cause-specific account in the registry record. These are descriptive figures, not evidence of a statistically established difference. The record's serious-event terms are accompanied by percentages, but it does not give enough context to use those terms as a comparative analysis.
General: a point estimate describes the observed effect, while a confidence interval describes the range of estimates reasonably compatible with the data under the analysis assumptions. Statistical significance alone would not establish clinical importance, and lack of significance would not establish equivalence. Here, the response estimates and their uncertainty are not reported in the registry record, so neither magnitude nor precision can be judged.
9. Statistical Methods Explained
The record identifies a randomized, unmasked Phase II trial with a crossover model. Those labels describe broad design features, but they do not provide a complete account of how outcomes were analyzed. The number of statistical analyses reported is 0. The registry record does not report the statistical analysis plan, the method used to compare response counts, or the handling of missing endpoint data.
What does randomization contribute?
General: random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. This supports a causal interpretation of a between-group contrast when the analysis follows the randomized assignment and other design requirements are met. Randomization does not guarantee that groups will be identical, especially in a trial of limited size, and it does not replace reporting baseline characteristics or the analysis population. The record identifies randomized arms but does not report the randomization procedure or allocation ratio.
How should a response count be analyzed?
The primary outcome is a count of participants meeting either complete-remission or partial-response criteria. General: a count can be reported for each group, but the count alone depends on how many participants were assessed in that group. A response proportion uses the number assessed as its denominator; a treatment comparison might then express the difference or another contrast between groups, with uncertainty. No response counts, denominators for the primary endpoint, comparative estimates, or confidence intervals are reported in the registry record. No statistical method for this binary outcome is specified there.
General: a confidence interval conveys uncertainty around an estimate and should be considered alongside the estimate itself. A wide interval indicates limited precision; a narrow interval indicates greater precision under the model and assumptions used. A p-value addresses compatibility of the observed data with a specified null hypothesis under a statistical model; it does not measure the probability that a treatment is effective or establish the importance of an effect. No such estimates or tests for the primary endpoint are reported in the registry record.
Why does the crossover structure matter?
The record names a crossover model and describes an outcome for the combinations when used after failure of the first regimen. General: crossover data contain information about treatment sequence as well as treatment received. A comparison of first-period outcomes can differ from an analysis that includes later treatment, because participants' later outcomes may be affected by prior treatment, time, or the reason for switching. A crossover analysis therefore needs to specify which period and sequence are being compared and how carryover or selection after failure is handled. The registry record does not report those analytic details or results for the crossover outcome.
The initial tolerability groups are described as non-randomized, whereas the two main treatment groups are described as randomized. General: non-randomized groups may differ for reasons associated with treatment selection, so a direct comparison with randomized groups does not have the same protection from confounding. The record does not state that these early groups were included in a primary randomized analysis, and no such analysis should be inferred from the arm listings.
What can planning calculations show?
General: sample-size planning calculations describe the number of participants that might be needed to detect a chosen effect under stated assumptions. They depend on assumptions about the effect to detect, the significance level, allocation, outcome variability, and analysis method. A planning illustration based on an observed effect is not an estimate of observed power and does not show what the trial was designed to detect. The record's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. The registry record does not report the trial's own sample-size justification. No planning result should be interpreted as a trial outcome.
General: for binary outcomes, assumptions about the event rate affect planning, while the observed response count and denominator are needed for interpretation after a trial. For time-to-event outcomes, the number and timing of events contribute to precision; the secondary outcomes include disease-free and overall survival, but their analyses and results are not reported in the registry record. The record does not specify methods for these outcomes, adjustment for covariates, or multiplicity control.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including response rate, crossover treatment after failure of the first regimen, thrombocytopenia mechanism, hairy cell leukemia biology, correlations involving measurable residual disease and tumor markers, measurable residual disease-free survival, disease-free survival, and overall survival. It also lists 12 outcome measures. With multiple outcomes, time points, or comparisons, the chance of at least one apparently unusual result can increase if many tests are conducted. General: a prespecified testing hierarchy or multiplicity adjustment can help define which results are confirmatory and how to interpret multiple statistical tests. The registry record does not report such a plan.
The primary endpoint is described at the end of treatment, approximately 6 months, while the brief summary describes four treatment cycles of 28 days each. The record does not report whether there were additional assessment times for the primary endpoint, how any repeated measurements were analyzed, or how outcome definitions were applied across treatment sequences.
Missing-data handling is not reported in the registry record. It does not say how participants without an end-of-treatment assessment were classified, whether any imputation was used, or how withdrawal or crossover affected the primary analysis. These decisions matter because the denominator and assumptions about missing outcomes can influence a binary response estimate.
The registry record does not identify an intention-to-treat, per-protocol, or safety analysis population for the primary endpoint. It also does not report protocol deviations or the number of participants analyzed for each outcome. Consequently, the enrollment figure should not be assumed to equal the number assessed for response. The record gives no basis for determining whether all randomized participants were retained in the primary analysis or how participants in the non-randomized tolerability groups were handled.
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 |
|---|---|---|---|
| Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | 0 | 6 | 0.0% |
| Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | 0 | 6 | 0.0% |
| Randomized to 90 mg/m^2 Bendamustine-Rituximab | 8 | 28 | 28.6% |
| Randomized to Pentostatin-Rituximab | 7 | 28 | 25.0% |
| Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | 0 of 6 |
| Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | 0 of 6 |
| Randomized to 90 mg/m^2 Bendamustine-Rituximab | 3 of 28 |
| Randomized to Pentostatin-Rituximab | 5 of 28 |
| Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab | 0 of 1 |
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 |
|---|---|
| Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | 6 of 6 |
| Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | 6 of 6 |
| Randomized to 90 mg/m^2 Bendamustine-Rituximab | 28 of 28 |
| Randomized to Pentostatin-Rituximab | 28 of 28 |
| Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to Pentostatin-Rituximab | Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab |
|---|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 6 | 0 of 6 | 3 of 28 | 2 of 28 | 0 of 1 |
| Lung infection | Infections and infestations | 0 of 6 | 0 of 6 | 2 of 28 | 2 of 28 | 0 of 1 |
| Upper respiratory infection | Infections and infestations | 0 of 6 | 0 of 6 | 1 of 28 | 2 of 28 | 0 of 1 |
| Acute kidney injury | Renal and urinary disorders | 0 of 6 | 0 of 6 | 1 of 28 | 1 of 28 | 0 of 1 |
| Allergic reaction | Immune system disorders | 0 of 6 | 0 of 6 | 0 of 28 | 2 of 28 | 0 of 1 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 0 of 6 | 0 of 28 | 2 of 28 | 0 of 1 |
| Sepsis | Infections and infestations | 0 of 6 | 0 of 6 | 1 of 28 | 1 of 28 | 0 of 1 |
| Syncope | Nervous system disorders | 0 of 6 | 0 of 6 | 2 of 28 | 0 of 28 | 0 of 1 |
| Chills | General disorders | 0 of 6 | 0 of 6 | 1 of 28 | 0 of 28 | 0 of 1 |
| Dehydration | Metabolism and nutrition disorders | 0 of 6 | 0 of 6 | 1 of 28 | 0 of 28 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Non-Randomized to 70 mg/m2 Bendamustine-Rituximab | Non-randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to 90 mg/m^2 Bendamustine-Rituximab | Randomized to Pentostatin-Rituximab | Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab |
|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 5 of 6 | 3 of 6 | 21 of 28 | 19 of 28 | 0 of 1 |
| Lymphocyte count decreased | Investigations | 0 of 6 | 0 of 6 | 23 of 28 | 22 of 28 | 0 of 1 |
| White blood cell decreased | Investigations | 4 of 6 | 4 of 6 | 15 of 28 | 21 of 28 | 0 of 1 |
| Platelet count decreased | Investigations | 4 of 6 | 5 of 6 | 19 of 28 | 14 of 28 | 0 of 1 |
| Chills | General disorders | 5 of 6 | 4 of 6 | 13 of 28 | 19 of 28 | 0 of 1 |
| Aspartate aminotransferase increased | Investigations | 5 of 6 | 3 of 6 | 18 of 28 | 9 of 28 | 0 of 1 |
| Neutrophil count decreased | Investigations | 2 of 6 | 3 of 6 | 15 of 28 | 15 of 28 | 0 of 1 |
| Alanine aminotransferase increased | Investigations | 5 of 6 | 2 of 6 | 13 of 28 | 11 of 28 | 0 of 1 |
| Fever | General disorders | 2 of 6 | 3 of 6 | 15 of 28 | 11 of 28 | 0 of 1 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 6 | 1 of 6 | 14 of 28 | 13 of 28 | 0 of 1 |
Serious events with the highest arm-level rate: febrile neutropenia (10.7%), allergic reaction (7.1%), dyspnea (7.1%), lung infection (7.1%), syncope (7.1%).
The safety record distinguishes serious adverse events from other adverse events and gives the number at risk and affected for each listed group. In the randomized bendamustine-rituximab group, 8 of 28 participants had a serious adverse event; in the randomized pentostatin-rituximab group, 7 of 28 did. These are descriptive counts. The registry record does not report a statistical comparison, confidence interval, or a definition of the analysis period for these figures, so they should not be read as evidence of a difference between regimens.
The record lists febrile neutropenia at 10.7%, and allergic reaction, dyspnea, lung infection, syncope, and upper respiratory infection at 7.1% each among the leading serious adverse event terms. These percentages describe the listed terms, but the registry record does not give their corresponding event counts in the registry record. A participant may experience more than one event; the record does not clarify whether term counts represent participants or events. The percentages therefore should not be added together or treated as mutually exclusive categories.
The randomized groups also have recorded deaths: 3 in the bendamustine-rituximab group and 5 in the pentostatin-rituximab group. The record does not provide causes or a statistical comparison. Death counts alone do not establish treatment attribution. Safety findings are best interpreted with their definitions, observation periods, denominators, and context, some of which are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that the trial was designed to study rituximab combined with pentostatin or bendamustine in multiply relapsed or refractory hairy cell leukemia. It identifies a randomized comparison between the combination regimens, a primary response endpoint, and several secondary outcomes. It also describes non-randomized tolerability groups and a crossover model. These features indicate the questions the investigators intended to address, but they do not establish the observed response to either regimen.
The primary endpoint results are not reported in the registry record. No response counts, response proportions, comparative estimate, confidence interval, or p-value are available in the record described. As a result, the direction, magnitude, and precision of the primary treatment comparison cannot be assessed. The same limitation applies to the listed secondary outcomes: their names are present, but their results and analyses are not reported.
The adverse-event record offers descriptive counts for serious adverse events and deaths in the randomized groups, plus percentages for selected serious event terms. Those figures do not by themselves establish a causal relationship, a treatment difference, or the comparative safety profile of the regimens. The record does not report the statistical comparisons or enough detail about event definitions and observation periods to support stronger conclusions.
General: a trial's design describes how evidence was intended to be collected; the result requires observed outcome data and a transparent analysis. A trial can be informative even when a registry record does not contain results, but the record alone cannot answer whether one treatment regimen produced more responses, how uncertain any difference was, or how outcomes changed after crossover. Those conclusions require results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises several useful statistical issues for clinical researchers. First, its record includes both randomized treatment groups and non-randomized tolerability groups. Keeping those groups distinct is important because randomization supports a different kind of comparison than treatment assignment based on a non-randomized process. Pooling all listed participants without regard to allocation could obscure what contrast a result represents.
Second, the crossover model means treatment sequence may matter. Outcomes during initial treatment and outcomes after a switch answer related but distinct questions. Clear reporting of the sequence, switching criteria, analysis period, and handling of prior treatment is necessary for readers to understand which effect an estimate represents. The record names crossover as an outcome of interest but does not report the detailed analysis.
Third, the trial's primary endpoint combines complete remission and partial response using defined clinical and laboratory criteria, while the registry record does not report the resulting counts or comparative estimates. This illustrates why a clear endpoint definition is only one part of an interpretable result. Denominators, missing-data handling, uncertainty, and the analysis population are also needed.
Finally, the stated objectives include comparison with rituximab alone, while the listed randomized arms describe the two combination regimens. The record does not resolve this difference. Transparent descriptions of objectives, comparator groups, and reported analyses are essential for aligning the question a trial asks with the evidence its results can support.
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 efficacy is that the registry record does not report the primary response counts or statistical analyses. Without those results, there is no basis for estimating the response in either randomized group or comparing them. The registry record also does not provide confidence intervals, p-values, or an analysis population for the primary outcome.
The registry describes a randomized comparison and a crossover model, but does not report the randomization procedure, allocation ratio, crossover criteria, treatment sequence results, or how later outcomes were analyzed. Its arm list also includes non-randomized tolerability groups, which are not interchangeable with randomized groups. The record does not explain how those groups relate analytically to the primary comparison.
The stated objective of comparing combinations with rituximab alone is not matched by a rituximab-alone randomized arm in the listed arm descriptions. The registry record does not explain this discrepancy. It also does not report the trial's sample-size justification, multiplicity approach, missing-data methods, or detailed analysis plan.
Safety interpretation is limited by the absence of reported comparative analyses and by missing context for selected event terms, including their event counts and observation details. The recorded deaths are not accompanied by causes in the registry record described. These limitations restrict conclusions to describing what the registry lists; they do not establish the treatment effect or the relative safety of the regimens.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia — NCT01059786.
- Registry record last updated 2026-10-15; status last verified 2026-09.
- Results first posted 2024-05-01.
- 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
This is a Phase II randomized, unmasked crossover trial of rituximab with pentostatin or bendamustine for multiply relapsed or refractory hairy cell leukemia. The registry lists enrollment of 69 and describes both non-randomized tolerability groups and randomized treatment groups. The primary endpoint counts participants achieving complete remission or partial response at the end of treatment, approximately 6 months.
The registry record does not report primary endpoint results or statistical analyses. It lists 12 outcome measures and secondary outcomes including response, crossover treatment, disease biology, measurable residual disease, disease-free survival, and overall survival. Serious adverse event counts and deaths are reported for the randomized groups, but no comparative safety analysis is reported.
The record is marked active, not recruiting, with primary completion on 2022-12-15. The detailed statistical plan, missing-data methods, multiplicity approach, and crossover analysis are not reported in the registry record.