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 Clofarabine for Relapsed or Refractory T-Cell or B-Cell Non-Hodgkin Lymphoma (NHL) (NCT00156013), a na phase 1, phase 2 study. The primary outcome is Phase I Maximum Tolerated Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00156013 |
| Phase | Phase 1, Phase 2 |
| Condition | Lymphoma, B-Cell, Lymphoma, Non-Hodgkin |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oncology Specialists, S.C. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns patients with relapsed or refractory lymphoma. Its official title specifies diffuse large cell B-cell non-Hodgkin lymphoma, while the brief description refers more broadly to non-Hodgkin lymphoma that has returned or resisted chemotherapy. The record does not report further eligibility details or the characteristics of the enrolled population.
Intervention
The drug under study was clofarabine. The arm description gives a regimen of 4 mg/m^2 on days 1-5 of each cycle, for a maximum of 6 cycles. The Phase I plan describes escalating dose cohorts, beginning at 4 mg/m2/day for 5 days.
Comparator
No separate control group is described. The study is listed as single-group, with allocation marked NA and masking marked NONE. Its design therefore does not provide a randomized, like-for-like comparison with another treatment or with no treatment.
Primary question
The primary endpoint is the Phase I maximum tolerated dose (MTD), expressed in mg/m^2. The question is what dose level meets the study's dose-escalation criteria for tolerability. The registry record describes the escalation plan, but does not report the resulting MTD or a numerical primary-endpoint result.
3. Trial Design
This completed study is recorded as Phase I/II and open-label. It is a single-group study rather than a randomized comparison: allocation is listed as NA, and masking as NONE. The registry lists an enrollment of 33. The record gives the study start as 2005-09 and primary completion as 2010-04.
The stated population is patients with relapsed or refractory non-Hodgkin lymphoma. The official title narrows this to diffuse large cell B-cell NHL. The record does not report the detailed eligibility criteria, baseline characteristics, or the number enrolled in each phase.
The intervention is clofarabine. The arm description specifies 4 mg/m^2 on days 1-5 of every cycle, for a maximum of 6 cycles. The primary endpoint description gives a Phase I dose-escalation plan: cohorts of 3 patients each were to receive increasing dose levels, starting at 4 mg/m2/day for 5 days and increasing in increments through 6, 8, 10, 12,…etc mg/m2/day for 5 days. It says the dose level immediately below the MTD would be used to treat patients in Phase II. The record does not explain how the listed arm regimen relates to the dose-escalation levels or report which dose was selected for Phase II.
Toxicity is listed as a secondary outcome. No control arm is reported, so any outcome description is within the clofarabine group and cannot establish a comparative treatment effect. The registry record does not report the analysis populations, detailed follow-up procedures, or results for the primary endpoint.
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 | Clofarabine |
|---|---|
| STARTED | 33 |
| COMPLETED | 31 |
| NOT COMPLETED | 2 |
Analysis population for the primary outcome, as defined in the registry: Per protocol guidelines for accrual to the cohorts.
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 | Clofarabine |
|---|---|---|
| Participants analysed | 33 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 13 |
| Age, Categorical: >=65 years | Participants | 20 |
| Age, Continuous | years | 69 (27 to 85) |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 14 |
| Region of Enrollment: United States | participants | 33 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I Maximum Tolerated Dose, measured over days 1 -28, maximum 6 cycles.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m^2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Phase I Maximum Tolerated Dose” and is measured in mg/m^2. It is a dose-finding endpoint: the study description sets out escalating dose cohorts, with the dose level immediately below the MTD intended for use in Phase II. The description says doses would be increased in increments, beginning at 4 mg/m2/day for 5 days, and that cohorts would include 3 patients each.
In general, an MTD endpoint is used in early-phase research to identify a dose level that satisfies prespecified tolerability criteria within a particular escalation plan. It is not itself a measure of comparative benefit. Its interpretation depends on the toxicity definitions, observation window, dose-limiting rules, and escalation or stopping decisions. Those operational details are not reported in the registry record, beyond the listed cohort and dosing plan.
The primary endpoint timeframe is described as days 1 -28, maximum 6 cycles. The registry record does not report an observed MTD, a numerical dose-level result, or a confidence interval. It therefore supports an explanation of what the endpoint was intended to measure, but not a conclusion about the dose selected or the precision of that estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a Phase I/II study of clofarabine in relapsed or refractory lymphoma, with the official title specifying diffuse large cell B-cell NHL. The study is completed and is listed as single-group and open-label. Its primary endpoint is the Phase I maximum tolerated dose, and the record describes a dose-escalation plan. However, no numerical MTD result is reported. The central primary-endpoint result therefore cannot be interpreted from the registry record.
The listed enrollment is 33. That number describes enrollment, not necessarily the number included in a particular endpoint analysis. The record does not report how many participants entered each dose cohort, completed treatment, or contributed evaluable data to the MTD assessment. It also does not give the criteria used to classify toxicity or make escalation decisions. Without these details and the endpoint result, it is not possible to assess how precisely the MTD was estimated or how the observed toxicities influenced dose selection.
The registry lists toxicity as a secondary outcome and includes adverse-event figures for clofarabine. The serious-event listing gives 33 at risk and 21 affected. For other adverse events, it gives 33 at risk and 33 affected. These are registry counts within the listed safety group; they do not constitute a comparison with another treatment. The record also names serious adverse-event terms, including neutropenic fever at 18.2% and pancytopenia at 9.1%. The registry does not report enough detail to determine from these figures alone the event-level definitions, timing, duration, severity grading, or whether events were judged related to treatment.
Because there is no control group, the safety figures cannot show how event rates compare with another regimen or with the underlying risks in this population. Likewise, the record does not provide a comparative efficacy estimate. The stated purpose and the endpoint plan should not be mistaken for a reported result: a dose-finding objective does not establish that a particular dose was selected, and the arm regimen does not substitute for a numerical MTD outcome.
Any result-based planning illustrations should be read separately from the trial design. The assumptions describe a hypothetical calculation using equal allocation between two arms, whereas this record describes a single-group study. Such illustrations are not the study's observed power or evidence of a randomized comparison. No sponsor analysis or primary outcome analysis is reported in the registry record.
9. Statistical Methods Explained
Several statistical ideas help distinguish the planned dose-finding question from the information actually reported. The registry describes an MTD endpoint and a dose-escalation scheme, but does not report the endpoint estimate or a detailed statistical analysis plan. The concepts below are general explanations, not claims about methods used in this study.
What does a dose-escalation endpoint ask?
In general, an early-phase dose-escalation study examines tolerability across dose levels to inform a dose choice for further study. The decision is governed by the protocol's definitions of dose-limiting toxicity, the interval in which toxicity is assessed, and rules for escalating, holding, or stopping. These rules are essential to interpret an MTD because the selected dose is a result of both observed toxicity and the design's decision process. The record describes cohorts of 3 patients each and increasing dose levels, but it does not report the dose-limiting toxicity definition or the rule that determined escalation.
The primary timeframe is listed as days 1 -28, maximum 6 cycles. A timeframe helps clarify when an outcome is meant to be assessed, but it does not by itself define which events count toward the dose decision or how repeated cycles are handled. Those details are not reported in the registry record.
What is the role of cohorts?
In general, cohort-based escalation assigns successive groups to dose levels and uses observed tolerability to guide what happens next. This is different from randomizing participants between concurrent treatment groups. The record's description says dose levels would increase from a starting dose of 4 mg/m2/day for 5 days, and that the dose immediately below the MTD would be used in Phase II. It does not report cohort-level enrollment, the toxicity findings at each dose, or how the selected dose was reached. Consequently, the planned sequence alone cannot reveal the actual dose-finding outcome.
What can a confidence interval tell a reader?
In general, a confidence interval communicates uncertainty around an estimated quantity. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. For an MTD estimate, uncertainty can be important because the data may be sparse at individual dose levels. No confidence interval, standard error, or other uncertainty estimate for the MTD is reported in the registry record. Precision therefore cannot be assessed from the primary endpoint information.
Why are analysis populations important?
In general, endpoint results can depend on which participants are included. A treated population, an eligible population, and a population meeting endpoint-evaluation criteria need not be identical. Dose-escalation assessments may require participants to have adequate observation at a given dose, while safety summaries may use a broader group. The registry lists enrollment and safety counts but does not define the analysis populations or explain handling of participants without complete endpoint assessment. Enrollment should not be treated as the analysis denominator for every outcome.
What does a single-group design allow?
In general, a single-group study can describe what occurred among participants receiving the study intervention, but it cannot directly estimate a randomized contrast against a concurrent control group. Differences from an external benchmark can be affected by population, follow-up, and measurement differences. Here, the record identifies a single-group design and does not report a control group. The safety entries and any within-group outcome therefore do not establish comparative effects.
How should planning calculations be interpreted?
In general, sample-size calculations depend on assumptions about the target effect, variability, significance level, allocation, and analysis. A planning illustration based on an observed effect is not a report of the trial's prospective design and is not observed power. The calculation assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. Those assumptions do not match the recorded single-group design. They should be read as hypothetical planning assumptions, not as evidence that this trial randomized participants between two arms or was designed around that allocation. The registry record does not report the trial's own sample-size justification.
The record lists no analyses. It does not report a statistical model, an adjustment strategy, a hypothesis test, or a numerical primary-endpoint result. A detailed statistical interpretation would require those results and the rules used to derive them; neither should be inferred from the dose-escalation description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint, Phase I Maximum Tolerated Dose, and toxicity as a secondary outcome. It also reports 3 outcome measures, but does not give a complete account of how each measure was analyzed or how results were prioritized. The record lists no analyses. A multiplicity strategy for handling several outcomes or repeated tests is not reported in the registry record.
In general, multiplicity matters when several outcomes, dose levels, time points, or statistical tests are examined. Testing many hypotheses can increase the chance of a nominally notable result arising by chance. A prespecified analysis plan can clarify which tests are confirmatory and whether adjustment is intended. The record does not report such a plan, so no conclusion about adjustment or the confirmatory status of any secondary result is warranted.
Missing-data procedures are not reported in the registry record. There is no description of how participants with incomplete follow-up, missed assessments, treatment discontinuation, or unevaluable toxicity data were handled. The listed enrollment and safety denominators do not establish that every participant had complete information for every endpoint.
Analysis populations are also not reported. The record does not specify whether the primary endpoint used all enrolled participants, participants treated at a dose level, or only participants meeting endpoint-evaluation criteria. These omissions limit the ability to reproduce or assess the endpoint analysis. They are particularly relevant to dose escalation, where adequate observation at a dose may affect whether a participant contributes to a decision.
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 |
|---|---|---|---|
| Clofarabine | 21 | 33 | 63.6% |
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 |
|---|---|
| Clofarabine | 33 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | Clofarabine |
|---|---|---|
| neutropenic fever | Infections and infestations | 6 of 33 |
| pancytopenia | Blood and lymphatic system disorders | 3 of 33 |
| Atrial fibrillation | Cardiac disorders | 2 of 33 |
| thrombocytopenia | Blood and lymphatic system disorders | 2 of 33 |
| tumor lysis syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 33 |
| Anemia | Blood and lymphatic system disorders | 1 of 33 |
| bilateral lower extremity celluiltis | Infections and infestations | 1 of 33 |
| arthralgia | Musculoskeletal and connective tissue disorders | 1 of 33 |
| fever of unknown origin | Infections and infestations | 1 of 33 |
| hyperglycemia | Endocrine disorders | 1 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Clofarabine |
|---|---|---|
| thrombocytopenia | Blood and lymphatic system disorders | 33 of 33 |
| neutropenia | Blood and lymphatic system disorders | 28 of 33 |
| anemia | Blood and lymphatic system disorders | 27 of 33 |
| nausea | Gastrointestinal disorders | 16 of 33 |
| fatigue | General disorders | 14 of 33 |
| hyperglycemia | Endocrine disorders | 14 of 33 |
| leukopenia | Blood and lymphatic system disorders | 14 of 33 |
| vomiting | Gastrointestinal disorders | 10 of 33 |
| creatinine | Blood and lymphatic system disorders | 7 of 33 |
| pain | General disorders | 7 of 33 |
Serious events with the highest arm-level rate: neutropenic fever (18.2%), pancytopenia (9.1%), atrial fibrillation (6.1%), thrombocytopenia (6.1%), tumor lysis syndrome (6.1%).
The registry lists clofarabine safety counts with 33 at risk for serious adverse events and 21 affected. For other adverse events, it lists 33 at risk and 33 affected. The record also lists serious adverse-event terms and percentages: neutropenic fever, 18.2%; pancytopenia, 9.1%; atrial fibrillation, 6.1%; thrombocytopenia, 6.1%; tumor lysis syndrome, 6.1%; and anemia, 3.0%.
These figures describe the safety entries for the clofarabine group; they are not a comparison with a control group. The term percentages should not be read as rates of unique participants unless the registry's event-counting rules establish that interpretation. The record does not report the definition of the safety analysis population, event-level denominators, timing, duration, severity grades, or attribution to treatment. Deaths are not reported in the safety entry.
In general, safety summaries require context about how events were collected and classified. The counts do not by themselves establish causation, and without a concurrent comparator they cannot show whether the listed frequencies differ from those under another treatment or from background risk in the study population.
12. What the Result Does, and Does Not, Mean
The registry record describes a completed Phase I/II investigation of clofarabine in relapsed or refractory non-Hodgkin lymphoma. Its primary question was dose finding: the Phase I endpoint was the maximum tolerated dose, with a plan to use the dose immediately below that level in Phase II. The record provides the intended escalation approach, but does not report a numerical MTD result. Therefore, it does not establish which dose was selected or how precisely the dose was estimated.
The listed safety entries indicate that adverse events were recorded in the clofarabine group, including serious adverse-event terms such as neutropenic fever and pancytopenia. These data describe reported events and affected counts in the registry. They do not, on their own, establish that clofarabine caused an event, quantify comparative risk, or show how safety compares with another option. There is no control group in the recorded design.
The study's title, intervention, and endpoint plan describe what was investigated; they are not equivalent to evidence of a clinical benefit. The registry record does not provide a numerical efficacy outcome, a comparative effect estimate, or an analysis of benefit. Nor does the absence of a reported primary result establish that no result was obtained; it means that the result is not reported in the registry record.
More complete interpretation would require the actual dose-level results, the operational toxicity criteria, the endpoint analysis population, and information about follow-up and missing assessments. For clinical researchers, the key distinction is between a planned early-phase dose-finding question and a demonstrated comparative outcome. This record supports the former description, but the primary dose result and a comparative efficacy conclusion are not reported.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and estimand must be kept distinct. The registry describes a single-group, open-label Phase I/II study with a dose-escalation objective. Its primary endpoint is a dose-selection quantity, not a treatment contrast. Understanding the design prevents readers from treating the safety counts or planned dose schedule as evidence from a randomized comparison.
The record also illustrates how a stated endpoint can be difficult to interpret without its result and decision rules. An MTD depends on observed toxicity across dose levels and on the criteria used to define an unacceptable level of toxicity. The record gives the intended cohort structure and escalation sequence, but not cohort-specific outcomes, the decision rules, or the numerical endpoint result. The protocol description therefore explains the question without answering it.
Safety summaries need similar care. Counts and percentages are useful descriptive information, but their interpretation depends on denominators, event definitions, collection methods, and whether repeated events are counted. Without a concurrent control group, descriptive event frequencies do not provide a comparative safety estimate.
Finally, planning calculations should not be mistaken for study-design details. The associated assumptions describe an equal-allocation, two-arm illustration, while the recorded trial is single-group. Keeping those purposes separate helps prevent hypothetical calculations from being interpreted as observed power or as evidence that the study included a randomized comparator. The record's omissions also show why transparent reporting of analysis populations, missing-data handling, and endpoint results matters for reproducibility.
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 primary limitation for interpreting the trial is that the registry record does not report a numerical result for the primary MTD endpoint. It describes a dose-escalation plan but omits the dose-level outcomes and the selected MTD. The record also does not report the toxicity criteria or escalation decision rules needed to understand how the result would have been derived.
The study is listed as single-group and open-label, with no comparator. Accordingly, the registry entries cannot support a randomized estimate of relative efficacy or safety. The record does not report a numerical efficacy result, and its listed safety outcomes are descriptive rather than comparative.
Although enrollment is listed as 33, the record does not report the number contributing to each phase, dose cohort, or endpoint analysis. It does not provide baseline characteristics, detailed eligibility criteria, analysis populations, missing-data handling, or follow-up completeness. These omissions limit assessment of representativeness and of possible differences between enrolled participants and those included in outcome summaries.
The listed serious adverse-event terms and percentages lack accompanying event definitions, severity grades, timing, and attribution details. Deaths are not reported in the safety entry. The record also lists no analyses and does not give a statistical analysis plan or multiplicity approach. These are limitations of the available registry reporting; they do not establish what information may exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clofarabine for Relapsed or Refractory T-Cell or B-Cell Non-Hodgkin Lymphoma (NHL) — NCT00156013.
- Registry record last updated 2017-11-29; status last verified 2017-10.
- Results first posted 2012-07-09.
- 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 describes a completed, open-label Phase I/II, single-group study of clofarabine for relapsed or refractory non-Hodgkin lymphoma. The official title specifies diffuse large cell B-cell NHL. Enrollment is listed as 33. The arm description gives clofarabine 4 mg/m^2 on days 1-5 of every cycle, for a maximum of 6 cycles.
The primary endpoint is Phase I Maximum Tolerated Dose, with a planned dose-escalation approach. Toxicity is listed as a secondary outcome. The registry record does not report a numerical MTD result, a control group, or a numerical efficacy estimate. Safety entries include serious and other adverse-event counts, along with several serious adverse-event terms and percentages. The record does not report analysis populations, missing-data methods, or the detailed rules used to determine the MTD.