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 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (NCT02406742), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants and Severity of AEs.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02406742 |
| Phase | Phase 1, Phase 2 |
| Condition | Leukemia, Lymphocytic, Chronic, B-Cell |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 47 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Celgene |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled subjects with chronic lymphocytic leukemia/small lymphocytic lymphoma. The registry reports enrollment of 47. The primary endpoint population is described as the Safety Population; further details about that population are not reported in the registry record.
Intervention
The study evaluated CC-122 as a single agent and in combinations with ibrutinib or obinutuzumab. The registry describes dose escalation for the single-agent arm and dose-finding cohorts for the combination arms. Exact administered dose levels and participant-level treatment histories are not reported in the registry record.
Comparator
This was a non-randomized study with parallel arms, not a randomized comparison. The arms therefore do not constitute like-for-like control groups. The registry record does not identify a separate untreated or standard-treatment control arm.
Primary question
The primary outcome asks how many participants experienced adverse events and how severe those events were, including dose-limiting toxicities, using NCI CTCAE criteria version 4.03. The registry also lists pharmacokinetic and preliminary efficacy outcomes, including best overall response and progression-free survival, but posted analysis results for those outcomes are not reported in the registry record.
3. Trial Design
This completed study was registered as Phase 1/2, open-label, non-randomized, and parallel. Its stated focus was safety, pharmacokinetics, and preliminary efficacy of CC-122 given alone and with ibrutinib or obinutuzumab in subjects with chronic lymphocytic leukemia/small lymphocytic lymphoma. The registry reports enrollment of 47. The listed study start was 2015-07-27, and primary completion was 2020-07-07.
The registry describes three treatment arms: CC-122 single agent; CC-122 with ibrutinib; and CC-122 with obinutuzumab. For the single-agent arm, it describes an intrasubject dose-escalation design. For the two combination arms, it describes ascending fixed-dose cohorts using a 3 + 3 dose-finding design. The descriptions state that the combination dose finding was intended to assess safety and tolerability and to identify dose levels for further study. Additional details in those arm descriptions are incomplete, so exact dose schedules and all operational rules are not reported in the registry record.
Open-label means the study was not masked, and non-randomized means treatment assignment was not made by random allocation. As a result, differences between the groups cannot be interpreted as randomized treatment effects. The arms may also differ in who entered them, their dose-escalation experience, and other features; the record does not provide enough information to assess those differences. The study’s phase 1/2 designation and dose-finding structure signal an emphasis on early safety and dose evaluation alongside preliminary efficacy and pharmacokinetics, rather than a controlled estimate of comparative benefit.
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: 46 participants treated
Overall Study
| Stage | Arm A | Arm B | Arm C |
|---|---|---|---|
| STARTED | 14 | 16 | 16 |
| Dose Escalation 1 | 3 | 0 | 0 |
| Dose Escalation 2 | 9 | 5 | 3 |
| Dose Escalation 3 | 2 | 3 | 3 |
| Dose Escalation 4 | 0 | 3 | 3 |
| Dose Escalation 5 | 0 | 5 | 5 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 14 | 16 | 16 |
Reasons for not completing this period:
| Reason | Arm A | Arm B | Arm C |
|---|---|---|---|
| Progression of Disease | 5 | 1 | 6 |
| Adverse Event | 3 | 0 | 2 |
| Death | 1 | 0 | 0 |
| Lack of Efficacy | 0 | 0 | 1 |
| Withdrawal by Participant | 1 | 2 | 0 |
| Physician Decision | 1 | 2 | 1 |
| Transition to other treatment | 2 | 0 | 1 |
| Other Reasons | 1 | 11 | 5 |
Analysis population for the primary outcome, as defined in the registry: Safety Population
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 | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|---|
| Participants analysed | 14 | 16 | 16 | 46 | |
| Age, Continuous | Years | 67.4 (SD 9.41) | 63.4 (SD 9.98) | 61.5 (SD 6.11) | 64.0 (SD 8.78) |
| Sex: Female, Male: Female | Participants | 4 | 8 | 2 | 14 |
| Sex: Female, Male: Male | Participants | 10 | 8 | 14 | 32 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 | 15 | 16 | 45 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 12 | 16 | 14 | 42 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants and Severity of AEs, measured over Approximately 60 Months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled “Number of Participants and Severity of AEs.” It counts adverse events and records their severity using NCI CTCAE criteria version 4.03; dose-limiting toxicities are included. The stated timeframe is approximately 60 months, and the outcome population is the Safety Population.
Counting participants with events and describing severity are useful in an early-phase dose-finding study because they give a structured account of tolerability across the treatment arms. Severity grading distinguishes events by seriousness of intensity, while attention to dose-limiting toxicities is relevant to decisions about dose escalation and selection of a dose for further evaluation. These are general purposes of such safety measures, not evidence that a particular dose was selected or that an event was caused by treatment.
The registry’s primary outcome is framed as a participant count and severity assessment, not as a comparative efficacy endpoint. The posted record does not report a formal treatment-effect estimate, confidence interval, or hypothesis test for this outcome. It also does not give a fuller description of how repeated events in the same participant were handled in the primary outcome. Those analysis details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes an early-phase study with three treatment arms and a safety-focused primary outcome. The posted adverse-event information reports serious adverse events in each arm, as well as other adverse events and deaths. In arm A (CC-122), 7 of 14 participants at risk were affected by serious adverse events, 14 of 14 by other adverse events, and 2 deaths were reported. In arm B (CC-122+Ibrutinib), 7 of 16 were affected by serious adverse events, 16 of 16 by other adverse events, and 0 deaths were reported. In arm C (CC-122+Obinutuzumab), 4 of 16 were affected by serious adverse events, 16 of 16 by other adverse events, and 1 death was reported.
These are descriptive results, not evidence that one regimen is safer than another. The study was non-randomized, and its arms are not like-for-like control groups. Differences in the counts may reflect differences in participant characteristics, treatment exposure, follow-up, dose escalation, or other factors; the registry record does not report enough detail to evaluate those possibilities. The counts alone do not establish whether an event was caused by a study drug.
The registry lists the most frequent serious-event terms with percentages: pneumonia, 21.4%; haemolytic anaemia, 14.3%; pyrexia, 7.1%; bacteraemia, 7.1%; candida sepsis, 7.1%; and enterococcal sepsis, 7.1%. The denominator and the precise derivation of these percentages are not reported in the registry record, so they should be read as posted descriptive figures rather than converted into participant counts or comparisons.
Although the registry lists secondary outcomes such as best overall response, minimal residual disease response rate, duration of response, and progression-free survival, it reports no analyses for the outcomes. The record therefore does not provide posted results from which to estimate response or time-to-event outcomes. It also does not provide comparative estimates or uncertainty intervals for the safety findings. The proper interpretation is limited to the posted descriptive safety data and the stated study design; conclusions about comparative efficacy or safety are not supported by this record.
9. Statistical Methods Explained
The study design determines what statistical conclusions can be drawn. This was a parallel-arm study, so participants were assigned to one of the listed regimens rather than all arms being repeated conditions for the same participant. It was also non-randomized and open-label. In general, random allocation helps balance both measured and unmeasured characteristics between groups, while masking can reduce some sources of assessment bias. Neither feature was present. This does not make descriptive reporting invalid, but it limits causal comparisons between arms.
What does dose finding mean?
The registry describes intrasubject dose escalation for the single-agent arm and ascending fixed-dose cohorts using a 3 + 3 design for the combination arms. In general, dose-finding designs gather safety information as doses are escalated or cohorts are evaluated, with the aim of identifying doses for further study. The registry says the combination-arm evaluation was intended to determine safety and tolerability and identify dose levels, but the full escalation rules, dose levels, and dose-selection results are not reported in the registry record. The design description alone should not be treated as evidence that a particular dose was established.
What do the safety counts represent?
A count of participants affected is different from a count of event episodes: a participant may experience more than one event, while a participant-level count records whether a person was affected. The posted results distinguish serious adverse events from other adverse events and give the number at risk in each arm. Those are useful descriptive summaries, but they do not provide event timing, duration, recurrence, exposure-adjusted rates, or individual-level detail. Such details are not reported in the registry record.
Severity classification provides a common framework for describing adverse events. The primary outcome names NCI CTCAE criteria version 4.03 and includes dose-limiting toxicities. In general, a grading system makes safety descriptions more consistent, but the posted primary outcome does not include a detailed breakdown by grade or a stated statistical comparison. The record also does not report a definition for how serious events or treatment-related events were adjudicated.
How should uncertainty be understood?
A confidence interval, in general, describes the range of effect estimates compatible with the data and a specified statistical procedure. It helps readers assess precision, not just the direction or size of an estimate. The registry record does not report confidence intervals for the posted adverse-event counts. Without intervals or a specified comparative analysis, it is not possible to judge statistical precision for differences between arms from the record alone.
For outcomes based on event counts, over-dispersion can matter when variability is greater than a simple count model assumes. In general, accounting for over-dispersion can produce more realistic uncertainty estimates. The record does not report a model for count outcomes, an over-dispersion assessment, or any corresponding adjusted estimates. No particular count model should therefore be attributed to the analysis.
What do the planning illustrations tell readers?
The registry includes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not evidence of the trial’s original design rationale, and the illustrations are not observed power. The record does not report the trial’s own sample-size justification. Because allocation was non-randomized and arms are not like-for-like controls, such hypothetical planning scenarios should not be read as a basis for comparative claims about the treatments.
For time-to-event outcomes, the stated planning approach counts total events using the Schoenfeld method; for other outcomes, it expresses sample size as participants per arm. In general, event-driven planning depends on the number of outcome events, while participant-based planning uses the number of people enrolled in each group. The record does not provide posted analysis results for the listed progression-free survival or duration-of-response outcomes, so readers cannot use the planning assumptions to infer their observed effects or precision.
What can be concluded from no posted analyses?
The registry reports zero analyses. It lists secondary outcome measures, but their presence in the outcome list is not the same as a posted result. No response estimate, pharmacokinetic summary, time-to-event estimate, or inferential comparison for those measures is reported in the registry record. The safety summaries can be described as recorded, but unreported analyses cannot be reconstructed from the arm descriptions or outcome names.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including plasma concentrations, best overall response, minimal residual disease response rate, duration of response, progression-free survival, maximum concentration, and time to maximum concentration. Examining many outcomes can raise a multiplicity issue: when several statistical tests are performed, the chance of at least one apparently unusual result can increase. In general, a prespecified testing hierarchy or adjustment may help control that issue. The statistical plan, any multiplicity adjustment, and any hierarchy for interpreting outcomes are not reported in the registry record. Because the record reports zero analyses, it does not show which outcomes were analyzed or how any multiplicity was handled.
Missing-data handling is also not reported in the registry record. The posted safety summaries identify participants at risk and those affected, but do not explain whether all participants contributed to each outcome, how incomplete follow-up was handled, or how missing event assessments were treated. For response and time-to-event measures, the registry lists outcomes but does not report analysis populations, censoring rules, or missing-data procedures.
The primary outcome names the Safety Population, but a detailed definition of that population is not reported in the registry record. The record also does not report an intention-to-treat population or another analysis-population definition for the secondary outcomes. These omissions limit reproducibility and make it difficult to assess whether the analyzed participants correspond to everyone enrolled or to a narrower group. No assumptions about missingness, exclusions, or analysis populations can be made from the registry entry alone.
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 |
|---|---|---|---|
| A (CC-122) | 7 | 14 | 50.0% |
| B (CC-122+Ibrutinib) | 7 | 16 | 43.8% |
| C (CC-122+Obinutuzumab) | 4 | 16 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| A (CC-122) | 2 of 14 |
| B (CC-122+Ibrutinib) | 0 of 16 |
| C (CC-122+Obinutuzumab) | 1 of 16 |
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 |
|---|---|
| A (CC-122) | 14 of 14 |
| B (CC-122+Ibrutinib) | 16 of 16 |
| C (CC-122+Obinutuzumab) | 16 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | A (CC-122) | B (CC-122+Ibrutinib) | C (CC-122+Obinutuzumab) |
|---|---|---|---|---|
| Pneumonia | Infections and infestations | 3 of 14 | 2 of 16 | 0 of 16 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 14 | 1 of 16 | 1 of 16 |
| Haemolytic anaemia | Blood and lymphatic system disorders | 2 of 14 | 0 of 16 | 0 of 16 |
| Sepsis | Infections and infestations | 0 of 14 | 1 of 16 | 1 of 16 |
| Diarrhoea | Gastrointestinal disorders | 0 of 14 | 1 of 16 | 0 of 16 |
| Stomatitis | Gastrointestinal disorders | 0 of 14 | 1 of 16 | 0 of 16 |
| Vomiting | Gastrointestinal disorders | 0 of 14 | 1 of 16 | 0 of 16 |
| Pyrexia | General disorders | 1 of 14 | 0 of 16 | 0 of 16 |
| Bacteraemia | Infections and infestations | 1 of 14 | 0 of 16 | 0 of 16 |
| Candida sepsis | Infections and infestations | 1 of 14 | 0 of 16 | 0 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | A (CC-122) | B (CC-122+Ibrutinib) | C (CC-122+Obinutuzumab) |
|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 5 of 14 | 6 of 16 | 13 of 16 |
| Diarrhoea | Gastrointestinal disorders | 3 of 14 | 7 of 16 | 4 of 16 |
| Nausea | Gastrointestinal disorders | 1 of 14 | 7 of 16 | 5 of 16 |
| Oedema peripheral | General disorders | 3 of 14 | 7 of 16 | 3 of 16 |
| Anaemia | Blood and lymphatic system disorders | 8 of 14 | 0 of 16 | 4 of 16 |
| Pyrexia | General disorders | 5 of 14 | 4 of 16 | 3 of 16 |
| Upper respiratory tract infection | Infections and infestations | 1 of 14 | 6 of 16 | 5 of 16 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 0 of 14 | 8 of 16 | 4 of 16 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 14 | 5 of 16 | 3 of 16 |
| Hypertension | Vascular disorders | 2 of 14 | 6 of 16 | 3 of 16 |
Serious events with the highest arm-level rate: pneumonia (21.4%), haemolytic anaemia (14.3%), pyrexia (7.1%), bacteraemia (7.1%), candida sepsis (7.1%).
The serious adverse-event summaries are participant counts by arm. Arm A (CC-122) reports 7 affected among 14 at risk; arm B (CC-122+Ibrutinib) reports 7 among 16; and arm C (CC-122+Obinutuzumab) reports 4 among 16. The posted figures for other adverse events are 14 among 14, 16 among 16, and 16 among 16, respectively. Deaths are reported as 2, 0, and 1 in those arms. These categories should be kept distinct: the record does not state that every death was an adverse event, nor does it give a cause for the deaths.
The serious-event terms are reported with percentages: pneumonia, 21.4%; haemolytic anaemia, 14.3%; pyrexia, 7.1%; bacteraemia, 7.1%; candida sepsis, 7.1%; and enterococcal sepsis, 7.1%. The record does not report the denominator or explain whether terms can overlap within participants. Therefore, these percentages should not be converted into counts or summed.
These figures are descriptive. The non-randomized arms are not comparable control groups, and the record does not provide exposure duration or adjusted event rates. Counts cannot establish comparative risk or causality.
12. What the Result Does, and Does Not, Mean
The record establishes that this completed Phase 1/2 study evaluated CC-122 alone and in combinations with ibrutinib or obinutuzumab, with safety, pharmacokinetics, and preliminary efficacy among its stated interests. Its primary outcome focused on the number and severity of adverse events, including dose-limiting toxicities. The posted safety information gives adverse-event counts and selected serious-event terms by arm. Those observations can be described as part of the registry’s record.
They do not establish that one regimen is safer or more effective than another. Treatment allocation was non-randomized, the study was open-label, and the arms were not like-for-like control groups. Differences in observed counts do not isolate the effect of treatment. The record does not report adjusted comparisons, uncertainty intervals, detailed participant characteristics, exposure-adjusted rates, or enough follow-up information to account for potential differences between arms.
The study’s listed secondary outcomes do not constitute posted findings. Best overall response, minimal residual disease response rate, duration of response, progression-free survival, and pharmacokinetic measures appear among the registered outcomes, but analyses for those outcomes are not reported in the registry record. Consequently, no conclusion about the magnitude or precision of efficacy or pharmacokinetic results can be drawn from this entry.
More generally, an early-phase dose-finding study can provide descriptive safety information and inform further research, but its design does not by itself establish a comparative treatment effect. The registry record does not report the dose-selection outcome, the full statistical analysis plan, or the trial’s sample-size justification. The narrow interpretation is therefore that the entry documents the design and selected safety summaries; it does not support broader claims about efficacy, comparative safety, or clinical use.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how design and analysis need to be read together. Its three arms represent a single-agent regimen and two combinations, but non-randomized allocation means that arm-to-arm contrasts are descriptive rather than controlled estimates. The distinction matters: a numerical difference in participant counts is not, by itself, evidence that the regimen caused that difference.
The dose-finding structure also shapes interpretation. The registry describes intrasubject escalation for the single-agent arm and 3 + 3 dose-finding cohorts for the combination arms. These designs are directed toward safety and dose evaluation. They are not equivalent to a randomized comparative trial, and their purpose should not be confused with testing a definitive efficacy claim.
The record further illustrates why registered outcomes and reported analyses are distinct. Several response, pharmacokinetic, and time-to-event measures are listed, yet the registry reports zero analyses. Without estimates and measures of uncertainty, readers cannot judge effect size or precision for those outcomes. The safety counts remain useful descriptions, but they answer a narrower question than a comparative analysis would.
Finally, planning illustrations based on observed effects are not observed power and do not explain the original design rationale. This distinction is important when considering whether a study was designed to detect a particular effect. The trial’s own sample-size justification is not reported in the registry record. Clear separation of observed data, hypothetical planning assumptions, and unreported analyses helps prevent conclusions from extending beyond what the record 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 record leaves important details unavailable for interpretation. The full arm descriptions are incomplete, so exact dose levels, schedules, and all escalation rules are not reported in the registry record. The entry does not report a full statistical analysis plan, the trial’s sample-size justification, or a detailed account of how participants entered each arm. These gaps limit assessment of how the design was implemented.
The posted safety results do not include confidence intervals, formal comparisons, event timing, exposure-adjusted rates, or detailed severity distributions. Although the primary outcome names CTCAE version 4.03 and includes dose-limiting toxicities, the record does not show a full breakdown of those measures. The denominator underlying the listed percentages for serious-event terms is not reported in the registry record.
The registry reports enrollment of 47, while the arm-level safety summaries list participants at risk for the three arms. The record does not explain the relationship between enrollment and those safety denominators, so it is not possible to determine from this entry alone how participants not represented in an arm-level summary were handled. No participant-level information is available to assess treatment exposure, follow-up, or reasons for missing outcomes.
Finally, the registry lists several secondary outcomes but reports zero analyses. Efficacy and pharmacokinetic results, missing-data procedures, multiplicity handling, and analysis populations beyond the named Safety Population are not reported in the registry record. These are limitations of what can be interpreted from this record, not evidence that the study did or did not conduct analyses outside the registry entry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma — NCT02406742.
- Registry record last updated 2021-09-20; status last verified 2021-08.
- Results first posted 2021-09-20.
- 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
This completed, open-label, non-randomized Phase 1/2 study evaluated CC-122 alone and with ibrutinib or obinutuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma. It used parallel arms and described dose escalation for the single-agent arm and 3 + 3 dose-finding cohorts for the combination arms. The registry reports enrollment of 47.
The primary outcome measured the number and severity of adverse events, including dose-limiting toxicities, using NCI CTCAE criteria version 4.03, over approximately 60 months. Posted safety summaries give participant counts for serious and other adverse events and deaths by arm, along with selected serious-event terms. The record reports zero analyses. Although response, pharmacokinetic, and time-to-event outcomes are listed, their results are not reported in the registry record. The non-randomized design and lack of posted comparative analyses mean that the arm-level safety counts should be interpreted descriptively.