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 Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer (NCT00546377), a na phase 1, phase 2 study. The primary outcome is Overall Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00546377 |
| Phase | Phase 1, Phase 2 |
| Condition | Leukemia, Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Previously treated patients with chronic lymphocytic leukemia or other low-grade B-cell neoplasms. The registry record lists leukemia and lymphoma as conditions. It does not give further eligibility details or describe the characteristics of participants who enrolled.
Intervention
The study concerns pentostatin, cyclophosphamide, rituximab, and mitoxantrone. The intervention list also names filgrastim, pegfilgrastim, sargramostim, and fluorescence in situ hybridization. The registry record does not explain the use or timing of each listed intervention.
Comparator
No separate comparator group is described. The study is identified as single-group, with allocation listed as NA and masking as none. Therefore, the record does not set up a like-for-like control comparison.
Primary question
The primary outcome is overall response, recorded as a number of participants and assessed over 3 years. The study description also identifies side effects and the best dose of mitoxantrone as questions of interest. The registry record does not report the overall-response result or a dose-selection result, so those questions cannot be answered from the posted results.
3. Trial Design
This is a phase I-II, single-group study listed as completed. The registry record describes a planned enrollment of 50 and identifies Memorial Sloan Kettering Cancer Center as the sponsor. The study start is recorded as 2005-07, and primary completion as 2014-05. The title and study description identify previously treated patients with chronic lymphocytic leukemia or other low-grade B-cell neoplasms.
Allocation is listed as NA, masking as none, and the model as single group. No separate control arm is described, so the design does not support a direct comparison with an untreated group or another regimen. The registry record does not report a randomization procedure, a masking procedure, or a control-group treatment.
The study description frames the work as assessing side effects and the best dose of mitoxantrone when given with pentostatin, cyclophosphamide, and rituximab, as well as examining how well the regimen works. However, the arm description contains no additional detail, and the registry record does not specify the dose levels, dose-escalation rules, treatment schedule, or dose-selection criteria. These aspects should not be inferred from the phase labels alone.
The intervention list contains the four named treatment agents, along with filgrastim, pegfilgrastim, sargramostim, and fluorescence in situ hybridization. The record does not explain the role, timing, or use of each item. It reports two outcome measures and zero analyses, but the posted results do not include a numerical primary response outcome. The completed status indicates the study's registry status, not that every planned outcome or analysis is reported.
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 | Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone |
|---|---|
| STARTED | 50 |
| COMPLETED | 43 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone |
|---|---|
| Deemed ineligible | 1 |
| Adverse Event | 6 |
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 | Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone |
|---|---|---|
| Participants analysed | 43 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 31 |
| Age, Categorical: >=65 years | Participants | 12 |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 35 |
| Region of Enrollment: United States | participants | 43 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response, measured over 3 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is overall response, recorded as a number of participants, with a 3 years timeframe. The registry description defines complete response through clinical assessment, including the absence of lymphadenopathy, hepatomegaly, or splenomegaly by physical examination and appropriate radiographic techniques when these findings were abnormal before treatment. It notes that stable mild abnormalities on CT scan may be compatible with complete response when other criteria are met.
Response assessment is described as ongoing, with assessment at a minimum before cycle four and after completion of therapy. For participants removed early, response status is to be determined at removal. The description emphasizes physical examination and assessment of peripheral blood and bone marrow in chronic lymphocytic leukemia; imaging is not required but may be repeated when abnormal before treatment.
In general, an overall-response endpoint captures whether participants meet specified response criteria, rather than measuring only a laboratory change or symptom at one moment. Such an endpoint can describe the proportion of a study group meeting the criteria when the response count and analysis denominator are reported. The registry record does not report the observed overall-response count or a response proportion, so the endpoint's result cannot be interpreted from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies overall response as the primary endpoint and lists its timeframe as 3 years, but it does not report the number of participants with an overall response. Without that result, the posted information cannot establish the observed response frequency or show how precisely it was estimated. A named endpoint is not itself an outcome finding.
The design is single-group, with no separate comparator. Any eventual response result from this design would describe outcomes among participants receiving the study regimen; it would not, by itself, isolate the regimen's effect from other explanations for change over time. In general, a concurrent comparator can help distinguish treatment-associated differences from changes that might also occur without the intervention. No such comparison is described in this registry record.
The enrollment field reports 50 participants, while the adverse-event group lists 43 participants at risk. These figures refer to different registry fields and should not be treated as interchangeable denominators. The record does not explain the relationship between them, report how many participants contributed to the primary outcome, or describe an analysis population. The primary response result therefore cannot be reconstructed from enrollment or safety data.
The safety information includes serious adverse-event data for the listed group, including 19 affected among 43 at risk. The record also lists other adverse events for 43 affected among 43 at risk, and gives several serious-event terms with percentages. These are safety descriptions, not evidence about the primary response endpoint. The record does not provide a confidence interval, comparative safety estimate, or a complete account of how adverse events were collected and summarized.
In general, a confidence interval expresses the range of estimates reasonably compatible with the data under a statistical model. No confidence interval for overall response is reported in the registry record. No p-value or statistical test result is reported either. Consequently, there is no basis in the posted results to assess statistical uncertainty around response or to make a formal comparison with another treatment.
The study description states that dose and side effects were of interest, but no dose-specific outcomes or dose-selection findings are reported. The record also does not report an interim analysis or a statistical analysis plan. These omissions limit what can be concluded about how the study addressed its stated questions; they do not establish that a particular analysis was or was not conducted outside the registry record.
9. Statistical Methods Explained
The registry record gives the broad design and endpoint description, but it does not report a statistical analysis plan, an analysis population, or a numerical primary-outcome result. The explanations below distinguish the general statistical concepts from the specific information recorded for this study.
What does a single-group design show?
In general, a single-group study describes outcomes in participants who receive the study intervention. It can estimate an outcome frequency in that group if the number meeting the endpoint and the relevant denominator are reported. It does not supply a concurrent comparison group. Without such a group, a difference between treatment and control cannot be estimated directly from the trial design.
For this study, the registry lists a single-group model and no masking. It does not describe a separate comparator. The primary outcome is a participant count for overall response, but that count is not reported. Thus, the design type and endpoint definition are available, while the primary numerical result and its precision are not.
How should a participant count be understood?
In general, a binary outcome classifies each participant into one of two categories, such as meeting or not meeting a response definition. A count records how many participants are in one category. To interpret a count as a rate or proportion, the denominator must be identified and the outcome assessment must be sufficiently described. A count alone does not show the uncertainty of the estimate.
The primary endpoint is recorded in participants, and its description sets out clinical criteria for response. The registry record does not state the response count or denominator. The enrollment value is 50, but the record does not establish that all enrolled participants were included in a primary-outcome analysis. It would therefore be inappropriate to infer a response proportion from enrollment.
What does a confidence interval add?
In general, a confidence interval communicates statistical uncertainty around an estimate. Its width depends on the data and the method used. It is not a guarantee that the true value lies inside a particular interval, and it does not address limitations such as selection effects or the absence of a comparator. No confidence interval for the primary response endpoint is reported in the registry record, so the precision of that outcome estimate cannot be assessed.
Why can event definitions and denominators matter?
In general, outcome summaries depend on the event definition, the period over which events are counted, and which participants are included. Safety reporting may distinguish serious adverse events from other adverse events and may summarize affected participants, event counts, or event terms. Those quantities are not interchangeable. A participant may have more than one event, and a term frequency does not necessarily correspond to a unique participant count unless the reporting method says so.
Here, the serious adverse-event group lists 43 at risk and 19 affected. A separate other-adverse-event entry lists 43 at risk and 43 affected. The registry record does not explain the precise counting rules, the follow-up period for these summaries, or whether participants could appear in multiple event terms. Serious-event term percentages are listed, but the denominator and method for those percentages are not further explained.
What statistical procedures are documented?
The record reports zero analyses and does not describe a statistical test, a model, an adjustment method, or a method for handling missing observations. It also does not report an interim-analysis plan, sample-size justification, or a dose-selection algorithm. In general, these details help readers understand how estimates were obtained and how planned decisions were connected to the data. Their absence from the registry record means those methods cannot be evaluated from the posted information.
The record includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is a hypothetical planning calculation, not observed power and not a description of the trial's own single-group design. The assumptions specify an equal-allocation two-arm framework, which is not the design listed for this study. They should not be read as evidence that the study randomized participants or included two arms. The record does not provide a study-specific sample-size justification.
In general, over-dispersion matters when the variability in observed data exceeds what a chosen statistical model expects. A model that does not account for over-dispersion can give uncertainty estimates that are too small. This concept is not a reported feature of the primary analysis for this study: the registry record does not identify a model or report an analysis that would allow over-dispersion to be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures, but reports zero analyses. It identifies overall response as the primary outcome. It does not give the other outcome's details in the posted results, nor does it describe how multiple outcomes or multiple statistical tests were handled. A multiplicity adjustment or testing hierarchy is not reported in the registry record.
In general, when several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. A pre-specified hierarchy or adjustment can address that issue, but the appropriate approach depends on the study questions and analysis plan. Because no analysis plan or test results are reported, it is not possible to determine whether multiplicity was considered or how it may have affected interpretation.
The registry record also does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. In general, missing outcome information can affect an estimate when participants with unobserved outcomes differ from those with observed outcomes. The primary endpoint description says response assessment is ongoing, sets minimum assessment points before cycle four and after therapy, and specifies that early removals have response status determined at removal. It does not report whether those assessments were completed for each participant or how incomplete records were treated analytically.
No primary analysis population is identified. The record does not state whether the response analysis included all enrolled participants, only those who received treatment, or another group. The enrollment value of 50 and the safety risk set of 43 do not resolve this question. As a result, neither the denominator for the primary endpoint nor the handling of missing outcomes can be established 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 |
|---|---|---|---|
| Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone | 19 | 43 | 44.2% |
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 |
|---|---|
| Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone | 43 of 43 |
Most frequent serious adverse event terms
| Event term | Organ system | Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone |
|---|---|---|
| Febrile neutropenia | Infections and infestations | 7 of 43 |
| Fever (in the absence of neutropenia) | General disorders | 5 of 43 |
| Nausea | Gastrointestinal disorders | 3 of 43 |
| Inf norm ANC/gr1/2 neut-Pneumonia(lung) | Infections and infestations | 2 of 43 |
| Pain - Head/headache | Investigations | 2 of 43 |
| Vomiting | Gastrointestinal disorders | 2 of 43 |
| Allerg react/hypersens (incl drug fever) | Immune system disorders | 1 of 43 |
| Allerg rhinitis (w sneez, nas stuff, postnas drip) | Immune system disorders | 1 of 43 |
| Colitis | Gastrointestinal disorders | 1 of 43 |
| Constipation | Gastrointestinal disorders | 1 of 43 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone |
|---|---|---|
| Glucose, high (hyperglycemia) | Metabolism and nutrition disorders | 31 of 43 |
| Hemoglobin | Metabolism and nutrition disorders | 31 of 43 |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | 31 of 43 |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | 31 of 43 |
| Lymphopenia | Blood and lymphatic system disorders | 28 of 43 |
| Platelets | Blood and lymphatic system disorders | 20 of 43 |
| Phosphate, low (hypophosphatemia) | Metabolism and nutrition disorders | 13 of 43 |
| ALT, SGPT | Metabolism and nutrition disorders | 9 of 43 |
| Bilirubin (hyperbilirubinemia) | Metabolism and nutrition disorders | 9 of 43 |
| Albumin, low (hypoalbuminemia) | Metabolism and nutrition disorders | 8 of 43 |
Serious events with the highest arm-level rate: febrile neutropenia (16.3%), fever (in the absence of neutropenia) (11.6%), nausea (7.0%), inf norm anc/gr1/2 neut-pneumonia(lung) (4.7%), pain - head/headache (4.7%).
The registry record lists a serious adverse-event group titled for pentostatin, cyclophosphamide, rituximab, and mitoxantrone. It reports 43 participants at risk and 19 affected. A separate other-adverse-event entry lists 43 at risk and 43 affected. These registry counts should be read as separate safety summaries, not as the primary response result.
The serious-event terms listed include febrile neutropenia at 16.3%, fever in the absence of neutropenia at 11.6%, and nausea at 7.0%. The record also lists infection with normal ANC or grade 1/2 neutropenia and pneumonia (lung) at 4.7%, pain in the head or headache at 4.7%, and vomiting at 4.7%. These term-level percentages describe the posted safety entries; the registry record does not further explain their calculation or whether a participant could contribute to more than one term.
In general, an affected-participant count is not the same as an event count: one participant can experience multiple events. Seriousness is also a classification, not a measure of how frequently every possible adverse event occurred. The follow-up period, collection procedures, and detailed safety-analysis methods are not reported in the registry record. Deaths are not reported in the registry record. These safety summaries alone do not permit a comparison with another regimen or a conclusion about overall safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase I-II, single-group study of a regimen containing pentostatin, cyclophosphamide, rituximab, and mitoxantrone in previously treated patients with chronic lymphocytic leukemia or other low-grade B-cell neoplasms. It identifies overall response as the primary endpoint and describes clinical criteria and assessment timing. It also records safety information for a group with 43 participants at risk, including 19 affected by serious adverse events.
However, the primary response count is not reported in the registry record. There is no numerical response estimate or confidence interval to interpret, and the record reports zero analyses. It therefore cannot establish the observed overall-response frequency or how precise such an estimate would be. The listed safety entries do not fill this gap because they concern adverse events rather than response.
The single-group design has no separate control arm. Even if a response result were available, this design would describe outcomes in the treated group rather than provide a direct comparison with another treatment. In general, a before-and-after observation or response frequency in one group cannot by itself distinguish the contribution of an intervention from other influences on outcomes.
The study description raises questions about side effects, mitoxantrone dose, and how well the regimen works. The registry record does not report dose-specific findings, an overall response result, or a statistical analysis plan. Those missing items prevent a full appraisal of the study's stated aims. The record supports description of the design, endpoint definition, enrollment, and posted safety figures; it does not support a conclusion about comparative effectiveness or a dose recommendation.
13. Why This Trial Matters Statistically
This study illustrates why a registry description and a numerical outcome result answer different statistical questions. The record identifies a clinically defined primary endpoint and explains when response assessment was intended to occur. Yet the number of participants meeting the endpoint and its analysis denominator are not reported. Without those values, readers cannot estimate the response frequency or judge its precision.
It also highlights the interpretive limits of a single-group design. A treatment group's outcomes can be described, but a comparator is needed for a direct estimate of how outcomes differ from another strategy. This matters especially when the study description asks how well a regimen works: a stated research question is not a comparative finding, and the design does not include a separate control group.
The safety entries show another important issue: an at-risk count, an affected-participant count, and a percentage attached to an event term are distinct kinds of summaries. Clear definitions, denominators, time periods, and analysis methods help readers understand what each quantity represents. The registry record gives some counts and term percentages but does not provide all of those explanatory details.
Finally, the record makes the boundary between design intent and reported analysis visible. It describes dose and response aims, but does not report a statistical plan, dose-selection findings, or primary response analysis. Careful statistical reading therefore depends not only on knowing the planned endpoint, but also on checking whether its result, uncertainty, denominator, and analytic context are reported.
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 the clinical outcome is that the registry record does not report the primary overall-response count, denominator, or estimate. Although the endpoint is defined and its timeframe is listed as 3 years, no numerical response result or confidence interval is available in the posted results.
The single-group design does not include a separate comparator. It cannot provide a direct between-group estimate, and the record does not describe a control treatment. The allocation field is NA and masking is listed as none. The registry record does not report detailed eligibility criteria, participant characteristics, or the reasons participants may not have contributed to each outcome.
The enrollment value is 50, while the safety group lists 43 participants at risk. The record does not explain this difference or indicate the primary-endpoint denominator. It also does not report missing-data counts, analysis-population definitions, or methods for handling incomplete outcome information. Consequently, the contribution of all enrolled participants to the primary analysis cannot be determined.
The study description refers to finding the best mitoxantrone dose, but dose levels, dose-escalation rules, and dose-specific results are not reported in the registry record. The statistical analysis plan, sample-size justification, interim analyses, and multiplicity procedures are also not reported. Safety details are limited: the collection period and event-counting conventions are not described, and deaths are not reported in the registry record. These limitations concern what can be evaluated from the registry record and should not be treated as proof that information was never collected elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer — NCT00546377.
- Registry record last updated 2016-05-12; status last verified 2016-04.
- Results first posted 2016-05-12.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record identifies a completed phase I-II, single-group study of pentostatin, cyclophosphamide, rituximab, and mitoxantrone in previously treated patients with chronic lymphocytic leukemia or other low-grade B-cell neoplasms. Planned enrollment is 50. The study start is recorded as 2005-07 and primary completion as 2014-05.
Overall response is the primary endpoint, recorded as a participant count with a 3 years timeframe. The endpoint description gives clinical assessment criteria and intended assessment points, but the response result is not reported in the registry record. The record lists serious adverse events for 43 participants at risk, with 19 affected, and gives several serious-event terms with percentages.
The model is single group, allocation is NA, masking is none, and zero analyses are listed. A comparator, numerical primary analysis, statistical analysis plan, dose-specific findings, and study-specific sample-size justification are not reported in the registry record. Interpretation is therefore limited to the design description, endpoint definition, enrollment, and posted safety summaries.