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 A Phase I/II Trial of VR-CHOP in Lymphoma Patients (NCT00634179), a na phase 1, phase 2 study. The primary outcome is Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00634179 |
| Phase | Phase 1, Phase 2 |
| Condition | Lymphoma, B-Cell, Follicular Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 37 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
The registry describes a study of VR-CHOP for patients with previously untreated indolent non-Hodgkin’s lymphomas, including follicular lymphoma and other low-grade B-cell lymphomas. Its stated primary objective is to determine whether the regimen provides benefit in this population. The primary outcome listed is a Phase I assessment of the maximum tolerated doses of bortezomib and vincristine when combined with rituximab and the CHOP chemotherapy regimen.
Population
Patients with untreated indolent non-Hodgkin’s lymphomas; the conditions named in the record include B-cell lymphoma and follicular lymphoma.
Intervention
VR-CHOP, comprising bortezomib, rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone.
Comparator
There is no separate control group in this single-group study. The record does not describe a randomized comparison.
Primary question
What maximum tolerated doses of bortezomib and vincristine can be used in combination with the other regimen components during Phase I?
A secondary outcome concerns the overall response rate, defined in the record as complete response, complete response unconfirmed, or partial response, according to International Workshop to Standardize Response Criteria criteria. The record does not include a numerical response estimate. It also does not report a numerical maximum tolerated dose or its confidence interval. Thus, the registered questions can be described, but the posted results do not allow the clinical outcomes to be quantified or compared with another treatment.
3. Trial Design
This was a Phase I/II, open-label, single-center, single-group trial sponsored by Emory University. The registry lists an enrollment of 37 and a completed status. The recorded start is 2008-02, and primary completion is recorded as 2015-11. Allocation is listed as not applicable, consistent with the absence of a randomized allocation or separate control arm. Participants and clinicians knew which regimen was being given.
The treatment regimen included bortezomib on days 1 and 8; rituximab, doxorubicin, cyclophosphamide, and vincristine on day 1; and prednisone on days 1-5. Treatment was scheduled to repeat every 21 days for up to 8 courses, in the absence of disease progression. The registry describes the Phase I safety group as induction and the Phase II group as maintenance. It does not provide enough detail to establish the full relationship between these phases or to reconstruct all treatment procedures.
The primary outcome is a Phase I maximum tolerated dose assessment for bortezomib and vincristine in combination. The record also lists an overall response rate outcome. The posted results include adverse-event counts for the Phase I induction and Phase II maintenance groups, but do not report numerical efficacy or dose-finding results. There is no randomized treatment contrast to interpret. The enrollment figure is a registry characteristic, not evidence of how many participants contributed data to each efficacy analysis; analysis populations and outcome-specific denominators are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 37 patients were enrolled. However, not all patients participated in both phases of this study. For phase I, 19 patients were enrolled, and for phase II, 30 patients were enrolled.
Phase I: Induction
| Stage | Treatment (VR-CHOP Regimen) |
|---|---|
| STARTED | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 0 |
Phase II: Maintenance
| Stage | Treatment (VR-CHOP Regimen) |
|---|---|
| STARTED | 30 |
| COMPLETED | 29 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Treatment (VR-CHOP Regimen) |
|---|---|
| Diagnosis changed after re-review | 1 |
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: A total of 37 patients were enrolled on this study. However, not all patients participated in both phases of this study. For phase I, 19 patients were enrolled, and for phase II, 30 patients were enrolled.
| Characteristic | Unit | Treatment (VR-CHOP Regimen) |
|---|---|---|
| Participants analysed | 37 | |
| Age, Continuous | years | 58 (28 to 71) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 20 |
| 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 | 11 |
| Race (NIH/OMB): White | Participants | 26 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 37 |
6. Primary Endpoint
The registry lists the primary outcome as Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I), measured over Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | mg/m^2 |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled as the maximum tolerated doses of bortezomib and vincristine when used with bortezomib, rituximab, and the CHOP chemotherapy regimen. The unit is mg/m^2, and the listed measure is a number with a 95% confidence interval. The timeframe entry includes “Cycle 1 for MTD” and also refers to CR following completion of therapy, up to 24 weeks. That wording combines different outcome concepts, and the registry record does not clarify the relationship between them.
In general, a maximum tolerated dose outcome is used in early-phase research to characterize dose tolerability within a particular combination and study context. It is not, by itself, an estimate of comparative benefit. A confidence interval expresses uncertainty around an estimate; its width depends on the information available and the analysis used. The registry record does not report the dose estimate, confidence interval limits, dose levels assessed, or the method used to determine the maximum tolerated dose. It therefore does not show what dose was identified or how precisely it was estimated.
The record also lists overall response rate as a secondary outcome, combining complete response, complete response unconfirmed, and partial response under the stated response criteria. No response numerator, denominator, estimate, or confidence interval is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes that this was a completed, single-group Phase I/II study with an enrollment of 37. It identifies an early-phase dose-tolerability question and a secondary response-rate question in patients with untreated indolent lymphomas. However, it does not provide numerical results for either the maximum tolerated dose or the overall response rate. Without those estimates, the registered efficacy and dose-finding questions cannot be answered from the posted results.
There is no randomized or concurrent control group. Consequently, the trial does not provide a like-for-like estimate of how VR-CHOP compares with another regimen. Changes in disease status in a single group, even if reported, would not alone establish that the treatment caused those changes. In this record, the outcome figures needed to describe response are absent as well. The registry’s stated objective that the regimen provide benefit is an objective, not a finding.
The adverse-event entries give counts of participants at risk and affected in Phase I induction and Phase II maintenance. They should be read as descriptive counts for those registry groups, not as a randomized comparison. The groups have different denominators, and the record does not explain their overlap, the period during which events were collected, or whether every participant in the overall enrollment contributed to each group. The reported counts therefore do not establish a comparative safety rate across treatment strategies.
The record lists a 95% confidence interval as the primary outcome’s dispersion measure, but supplies no interval limits or point estimate. No uncertainty around the response rate is reported either. Precision cannot be assessed without the actual estimates and their denominators. The posted results also contain no analysis entries, so there is no reported statistical test or adjusted estimate to interpret.
A separate planning illustration is described as based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Such a planning exercise is not the trial’s design, observed power, or evidence from a randomized comparison. Because no observed effect or resulting planning values are included in the registry record, the illustration cannot supply the missing clinical outcome estimates.
9. Statistical Methods Explained
The registry identifies the trial as Phase I/II and single-group, but it does not report the detailed statistical analysis plan. The outcome labels indicate the questions the study intended to address; they do not establish the exact methods used to collect, summarize, or analyze the data. The following statistical explanations are general and should not be mistaken for methods confirmed by this record.
What does a maximum tolerated dose measure?
In general, a maximum tolerated dose is a dose-finding concept: it concerns tolerability at tested dose levels under a specified treatment regimen and observation period. It is not a universal property of a drug, because the result depends on the regimen, patient population, dose schedule, event definitions, and dose-finding rules. Here, the registered endpoint names bortezomib and vincristine in combination with the other regimen components and gives Cycle 1 as the timeframe for MTD. The record does not report the dose levels, dose-escalation rules, toxicity criteria, or decision rule used to identify the maximum tolerated doses. It is therefore not possible to reconstruct the dose-finding procedure or judge how the dose conclusion was reached.
How should a confidence interval be understood?
In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. It is not a guarantee that the true value lies in one particular interval, nor does it by itself show clinical importance. A narrow interval generally indicates greater precision than a wide interval, while the point estimate gives the central estimated value. The primary outcome lists a 95% confidence interval, but neither the estimate nor the interval limits appear in the posted results. Its precision therefore cannot be evaluated. No confidence interval is listed for the response outcome in the record.
What does a single-group design permit?
In general, a single-group study can describe outcomes observed among participants receiving the study regimen. Without a concurrent control group, it cannot separate treatment effects from other explanations such as the natural course of disease, participant selection, or differences in assessment. An open-label design means that clinicians and participants know which treatment is being given. General methodological concern in an open-label study is that awareness of treatment can influence subjective assessments or care, although the record does not report whether such effects occurred. The study’s design is not a like-for-like comparison of treatment arms.
What does the response-rate definition contribute?
The secondary outcome defines overall response as the combined categories of complete response, complete response unconfirmed, and partial response, using International Workshop to Standardize Response Criteria criteria. In general, a combined response measure depends on consistent definitions, assessment timing, and complete outcome ascertainment. The registry record does not report the number of participants assessed, the response counts, the handling of unevaluable participants, or an estimate with uncertainty. The definition alone cannot show how many participants responded.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variation in count data is greater than a model assumes. If a count model ignores that extra variation, standard errors can be too small and confidence intervals or tests can appear more certain than warranted. Whether this issue is relevant depends on the data structure and model. The registry record does not report a count model, a dispersion estimate, or an analysis of over-dispersion, so no such method can be attributed to this trial.
What can the planning illustration say?
In general, a sample-size calculation describes the amount of information a hypothetical design might need under stated assumptions. The registry’s planning description uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a fraction of an observed effect. These assumptions are explicitly described as a planning illustration rather than the trial’s own design. The study itself is single-group, and the record does not supply the observed effect or numerical planning estimates. Such calculations are not observed power and do not replace the missing results.
More broadly, the registry record does not report a statistical analysis plan, outcome-specific analysis populations, methods for confidence intervals, missing-data procedures, or prespecified subgroup analyses. Those omissions prevent a detailed appraisal of model choice, assumptions, and robustness.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary Phase I maximum tolerated dose outcome and a secondary overall response rate outcome. It does not describe a testing hierarchy, a family of confirmatory hypotheses, or a procedure for controlling multiplicity. Whether multiplicity adjustment was planned or performed is not reported in the registry record. Without the analysis plan and numerical results, it is not possible to determine whether multiple outcomes or dose-related analyses were treated as exploratory or confirmatory.
Missing-data handling is also not reported in the registry record. The record does not explain how participants with incomplete treatment, missing response assessments, or unevaluable outcomes were handled. It does not describe imputation, censoring, or sensitivity analyses. These omissions matter because an outcome estimate can depend on who was included and how unavailable measurements were treated.
Analysis populations are not reported in the registry record. The enrollment is 37, while the adverse-event groups list 19 at risk for Phase I induction and 29 at risk for Phase II maintenance. Those figures do not identify the population used for the primary or secondary efficacy outcome. The record does not explain how many participants began each phase, completed the planned assessments, or contributed to a particular analysis. It would therefore be inappropriate to assume that the enrollment count is the denominator for each result.
Interim analyses, stopping rules, protocol deviations, and sample-size justification are not reported in the registry record. The separate planning assumptions described for sample-size illustrations are not evidence of the trial’s original design calculations. These gaps limit assessment of selective reporting and of how the reported results relate to the intended analysis plan.
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 |
|---|---|---|---|
| Phase I: Induction | 3 | 19 | 15.8% |
| Phase II: Maintenance | 1 | 29 | 3.4% |
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 |
|---|---|
| Phase I: Induction | 16 of 19 |
| Phase II: Maintenance | 22 of 29 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I: Induction | Phase II: Maintenance |
|---|---|---|---|
| Thrombosis | Blood and lymphatic system disorders | 1 of 19 | 0 of 29 |
| Fatigue | General disorders | 0 of 19 | 1 of 29 |
| Vomiting | Gastrointestinal disorders | 0 of 19 | 1 of 29 |
| Diarrhea | Gastrointestinal disorders | 0 of 19 | 1 of 29 |
| Pain | Nervous system disorders | 0 of 19 | 1 of 29 |
| Febrile Neutropenia | Blood and lymphatic system disorders | 1 of 19 | 0 of 29 |
| Anxiety/Depression | Psychiatric disorders | 0 of 19 | 1 of 29 |
| Cellulitis | Skin and subcutaneous tissue disorders | 0 of 19 | 1 of 29 |
| Dehydration | Metabolism and nutrition disorders | 0 of 19 | 1 of 29 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0 of 19 | 1 of 29 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I: Induction | Phase II: Maintenance |
|---|---|---|---|
| Neuropathy | Nervous system disorders | 16 of 19 | 22 of 29 |
| Neutropenia | Blood and lymphatic system disorders | 13 of 19 | 14 of 29 |
| Nausea | General disorders | 13 of 19 | 2 of 29 |
| Pain | Nervous system disorders | 12 of 19 | 1 of 29 |
| Fatigue | General disorders | 11 of 19 | 1 of 29 |
| Vomiting | Gastrointestinal disorders | 9 of 19 | 2 of 29 |
| Diarrhea | Gastrointestinal disorders | 7 of 19 | 1 of 29 |
| Thrombocytopenia | Blood and lymphatic system disorders | 4 of 19 | 3 of 29 |
| Low Potassium | Metabolism and nutrition disorders | 4 of 19 | 2 of 29 |
| Rash | Skin and subcutaneous tissue disorders | 4 of 19 | 0 of 29 |
Serious events with the highest arm-level rate: thrombosis (5.3%), febrile neutropenia (5.3%), extravasation (5.3%), fatigue (3.4%), vomiting (3.4%).
The registry reports adverse-event groups titled Phase I: Induction and Phase II: Maintenance. For Phase I induction, 19 participants were listed at risk for serious adverse events and 3 were affected; 19 were listed at risk for other adverse events and 16 were affected. For Phase II maintenance, 29 were listed at risk for serious adverse events and 1 was affected; 29 were listed at risk for other adverse events and 22 were affected. These are descriptive counts for the named groups, not results from a randomized safety comparison.
The record lists thrombosis, febrile neutropenia, and extravasation at 5.3% each among the top serious terms. Fatigue, vomiting, and diarrhea are each listed at 3.4%. The registry record does not clarify the denominator or event-collection details for these percentages, so they should not be converted into participant counts or treated as directly comparable between phases. The listed terms also do not, by themselves, establish that the regimen caused the events.
Death counts are not reported in the registry record. The counts do not describe event severity beyond the registry’s serious versus other grouping, timing, recurrence, or duration.
12. What the Result Does, and Does Not, Mean
The registered study addresses two distinct kinds of questions. Its Phase I primary outcome concerns tolerated doses of bortezomib and vincristine in a combination regimen. Its secondary outcome concerns the proportion of participants meeting the specified response categories. These questions are clinically and statistically different: a dose-tolerability estimate does not establish response, and a response estimate would not by itself identify the maximum tolerated dose.
The posted results do not provide a numerical estimate for either outcome. As a result, they do not show the dose identified, the precision of a dose estimate, or the response rate. The registry’s statement of a primary objective is not a report that the objective was met. No conclusion about treatment benefit or lack of benefit can be drawn from the absence of these numerical results.
The trial’s single-group design also limits what it could establish about comparative effects. It has no separate control arm and no randomized comparison. In general, outcomes from one treatment group cannot determine what would have happened to similar participants under another treatment. The record’s adverse-event counts offer descriptive safety information, but they do not establish a causal relationship or comparative safety advantage.
The enrollment of 37 describes the registered study size. It does not establish the number included in each outcome analysis, and the registry lists different at-risk counts for the Phase I and Phase II adverse-event groups. Because the outcome-specific denominators and analysis populations are not reported, precision and completeness cannot be assessed from the enrollment figure alone.
Any sample-size illustration based on a fraction of an observed effect is a planning exercise under stated assumptions, not evidence that a particular effect was observed or that the study had a given probability of detecting it. The registry record does not report the effect estimate needed to interpret such a calculation. The central result is therefore that the record defines intended questions and provides some adverse-event counts, while leaving the efficacy and dose-finding estimates unavailable.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines an early-phase dose-finding objective with a later-phase response question in a single-group study. Those objectives require different summaries and interpretations. Dose-finding concerns the tolerability of specified doses within the regimen; response-rate estimation concerns the frequency of defined disease responses. Keeping those questions distinct is important when interpreting a Phase I/II record.
The design also illustrates why a registry’s study objective should not be confused with an outcome result. The record states that the study sought to determine whether VR-CHOP provides benefit, but the posted results do not give a response estimate. The primary dose outcome likewise includes a measurement unit and confidence-interval specification without the estimate or interval limits. The intention to measure an outcome does not supply evidence about its observed value.
Single-group evidence has a different inferential scope from randomized comparative evidence. It can be useful for describing treatment experience and for addressing feasibility or dose questions, but it cannot provide a randomized contrast against another treatment. Here, allocation is listed as not applicable and the model as single group. Therefore, statistical interpretation should focus on the registered questions and the descriptive information actually present, rather than implying a treatment comparison.
The record also shows why denominators and analysis populations matter. Overall enrollment is 37, whereas adverse-event groups list different numbers at risk. Without outcome-specific denominators, missing-data procedures, and analysis definitions, it is difficult to judge completeness or precision. These are not minor details: they determine what population an estimate describes and how much uncertainty accompanies it.
Finally, the distinction between planning calculations and observed results is essential. A hypothetical sample-size illustration relies on assumptions about allocation and an effect to detect. It is not the trial’s own design or observed power, particularly when the clinical study has no two-arm randomized contrast. The available record supports a careful account of design and reporting limitations, not a numerical efficacy conclusion.
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.
Several limitations specific to this record constrain interpretation. First, the study is open-label, single-center, and single-group. There is no concurrent control arm, and the record does not describe randomization. Accordingly, it cannot support a like-for-like comparison with another treatment. Open-label assessment can also be vulnerable in general to awareness-related influences, although the record does not report whether these affected any assessment.
Second, the registry gives no numerical primary maximum tolerated dose, confidence interval limits, or response-rate estimate. The listed timeframe for the primary outcome combines “Cycle 1 for MTD” with language about complete response after therapy, up to 24 weeks; the relationship between those phrases is not clarified. The record also does not specify the dose-finding rules or the toxicity definitions used to identify the maximum tolerated dose.
Third, analysis populations, outcome denominators, and missing-data methods are not reported in the registry record. The adverse-event group counts do not resolve who contributed to the efficacy outcomes or how participants moved between phases. The record does not explain whether the Phase I induction and Phase II maintenance groups overlap, or give detailed event-collection periods. Death counts are not reported.
Finally, the statistical analysis plan, multiplicity approach, interim analyses, stopping rules, and sample-size justification are not reported in the registry record. The response outcome is defined, but no response counts or uncertainty estimates are available. These gaps mean that neither the results’ precision nor their robustness can be appraised, and the available information does not establish a comparative treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I/II Trial of VR-CHOP in Lymphoma Patients — NCT00634179.
- Registry record last updated 2016-10-27; status last verified 2016-09.
- Results first posted 2016-03-15.
- 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, single-center Phase I/II, single-group trial sponsored by Emory University, with an enrollment of 37. It concerns VR-CHOP for previously untreated indolent non-Hodgkin’s lymphomas and names a Phase I maximum tolerated dose outcome for bortezomib and vincristine, plus a secondary overall response rate outcome.
The regimen lists bortezomib, rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone, with treatment repeated every 21 days for up to 8 courses in the absence of disease progression. The posted results include adverse-event counts for Phase I induction and Phase II maintenance. They do not include numerical maximum tolerated dose or response-rate results, and do not report analysis populations, missing-data methods, or the statistical analysis plan.
Because the study has no control group, it does not provide a randomized comparison. The available record supports description of the design and reported safety counts, but not a numerical conclusion about efficacy or comparative effects.