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 SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma (NCT04762160), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04762160 |
| Phase | Phase 2 |
| Condition | Follicular Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Epizyme, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had relapsed or refractory follicular lymphoma and had previously received at least 2 standard systemic treatment regimens, including at least 1 anti-CD20-based regimen. The primary endpoint description specifies participants with wild-type (WT) EZH2 status. The registry record says five participants enrolled and only three were evaluable, but does not report the number of evaluable participants with WT EZH2 status.
Intervention
The study examined tazemetostat in combination with rituximab. The arm description states that tazemetostat 800 mg BID was administered daily from Cycle 1 Day 1 through the end of Cycle 24, or until disease progression, unacceptable toxicity, or withdrawal of consent. The available description of rituximab administration is incomplete, so its full schedule and route are not reported in the registry record.
Comparator
There was one treatment group and no randomized comparator. The registry describes a single-group, open-label design, with allocation listed as not applicable. Consequently, the study was not structured to compare the combination directly with another treatment or a control group.
Primary question
The primary endpoint was objective response rate among participants with WT EZH2 status. Response was defined as complete response or partial response according to the 2014 Lugano Classification, assessed by the investigator and a blinded independent review committee. The endpoint was planned for assessment during Cycles 3, 6, 12, 18, and 24. The registry reports no summary statistics for this endpoint because the trial terminated early and only three participants were evaluable.
3. Trial Design
SYMPHONY-II was a phase II, open-label, multicenter, single-group trial of oral tazemetostat combined with rituximab in participants with relapsed or refractory follicular lymphoma. The registry record identifies Epizyme, Inc. as the sponsor. With no randomized control arm, the design describes outcomes in participants receiving the combination rather than estimating a comparative treatment effect against another group.
The study enrolled five participants. The registry states that it was terminated early for business reasons and that only three participants were evaluable. The study start date was 2020-12-15, and the primary completion date was 2022-03-22. The record does not report a fuller account of the business reasons or the timing of the termination decision.
The arm description says tazemetostat 800 mg BID was administered daily from Cycle 1 Day 1 through the end of Cycle 24, for 24 months of therapy, or until disease progression, unacceptable toxicity, or withdrawal of consent. The rituximab administration description is cut off in the registry record; the full administration schedule is therefore not reported there.
Alongside objective response rate, the listed secondary outcomes include progression-free survival, duration of response, objective response rate in a subset with mutant EZH2 status, and objective response rate in rituximab-refractory participants. The record lists five outcome measures, but the available named secondary outcomes do not provide results for these measures. A detailed protocol, the reasons for selecting the enrollment target, and the statistical analysis plan 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: This study was to include a 28-day screening period, a 2-year (24-cycle) treatment period, and a follow-up period. In treatment period, participants were to be treated in 28-day cycles with tazemetostat in combination with rituximab through Cycle 6 then tazemetostat alone through Cycle 24, for 24 months of therapy or until disease progression, unacceptable toxicity, or withdrawal of consent. Overall 5 participants were enrolled in the study.
Overall Study
| Stage | Tazmetostat in Combination With Rituximab |
|---|---|
| STARTED | 5 |
| COMPLETED | 0 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Tazmetostat in Combination With Rituximab |
|---|---|
| Study terminated early due to business reasons | 5 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated early due to business reasons and only five participants were enrolled, of whom only three were evaluable. No summary statistics are available given the limited data from the small number of evaluable participants and individual participant data are also not presented to protect the privacy of the individuals.
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: The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of enhancer of zeste homolog 2 (EZH2) mutation status (mutant-type \[MT\] or wild-type \[WT\]).
| Characteristic | Unit | Tazmetostat in Combination With Rituximab |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 70.2 (SD 10.83) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 3 |
| Race/Ethnicity, Customized: White | Participants | 5 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or other Pacific Islander | Participants | 0 |
| Race/Ethnicity, Customized: Other/Unknown | Participants | 0 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 0 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate (ORR), measured over Planned to be assessed during Cycles 3, 6, 12, 18, and 24..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint, objective response rate, measures the proportion of participants meeting the definition of complete response or partial response. In this trial the endpoint applied to participants with WT EZH2 status, and response was defined using the 2014 Lugano Classification. The definitions distinguish complete from partial response using metabolic imaging criteria with PET-CT or radiologic criteria with CT, as described in the registry record.
Objective response rate is commonly used in clinical studies to summarize whether participants experienced a defined tumor response during a specified assessment period. It combines complete and partial responses into one endpoint; it does not by itself describe how long a response lasts. Duration of response and progression-free survival are listed as secondary outcomes, but their results are not reported in the registry record.
Assessment was planned during Cycles 3, 6, 12, 18, and 24. The investigator and a blinded independent review committee were to assess response. Independent review can provide an assessment separate from the investigator's, although the registry record does not report the review procedures or any comparison between the assessments.
No objective response rate estimate or other primary endpoint summary statistics are reported. The registry attributes the absence of summary statistics to early termination, five participants enrolled, and only three evaluable participants. Without an endpoint estimate, the magnitude and precision of the response outcome cannot be characterized from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is the small amount of evaluable data. The registry states that five participants enrolled, only three were evaluable, and the study terminated early for business reasons. It reports no primary endpoint summary statistics and does not present individual participant data. The posted results therefore do not provide an objective response rate estimate for the primary endpoint.
The primary endpoint was specifically defined for participants with WT EZH2 status. The record does not state how many of the evaluable participants had WT status, and it does not give response counts or a percentage. This prevents interpretation of the endpoint even as a simple descriptive proportion. It also means that the primary outcome cannot be assessed for precision from a confidence interval in the registry record.
The single-group design is another important boundary. Outcomes in participants receiving tazemetostat with rituximab cannot, on their own, establish how outcomes would compare with a different treatment or with no treatment. There is no randomized comparator to separate the treatment experience from other influences. The open-label design means participants and study personnel were not masked to treatment; the primary endpoint description nevertheless says a blinded independent review committee assessed response. Details of how that review was conducted are not reported.
The registry lists progression-free survival, duration of response, and subgroup objective response outcomes among the secondary measures. Their names indicate the kinds of outcomes intended for evaluation, but the registry record does not provide corresponding estimates in the information available. No conclusions about those endpoints can be drawn from their listing alone.
The safety record reports one participant with a serious adverse event among five at risk, five participants with other adverse events among five at risk, and zero deaths in the treatment group. Four serious adverse event terms are listed with 20.0% for each. These are descriptive counts and percentages from a very small group; they do not establish whether an event was caused by treatment, and the record does not report event timing or participant-level overlap between terms.
Any sample-size illustrations associated with the posted analysis should be read as planning scenarios under their stated assumptions, not as observed power or evidence that the trial could detect a particular effect. The registry does not report the trial's own sample-size justification. In the absence of the primary endpoint estimate and a comparator, the posted record supports only a limited description of enrollment, evaluability, design, and adverse-event reporting—not an estimate of comparative efficacy.
9. Statistical Methods Explained
Statistical methods determine how trial observations are converted into estimates and how uncertainty is described. The registry record reports the primary endpoint definition and assessment schedule, but it does not report a full statistical analysis plan. It gives no primary endpoint estimate, confidence interval, or analysis output. The explanations below distinguish general statistical principles from what can be established about this trial.
What does an objective response rate estimate?
In general, an objective response rate is a proportion: the numerator is the number of participants who meet a response definition, and the denominator is the number of participants included in the relevant analysis population. Here, the endpoint was defined for participants with WT EZH2 status and included complete or partial response under the 2014 Lugano Classification. The registry says five participants enrolled and three were evaluable, but it does not report the WT subgroup size or the number meeting either response category. No response proportion can therefore be described from the registry record.
The endpoint was planned for assessment during Cycles 3, 6, 12, 18, and 24. Repeated assessment points can describe response at different times, but the endpoint definition and analysis rules matter: for example, a plan must specify how a participant's responses across visits contribute to the final response classification. Such detailed rules are not reported in the registry record. The planned visits alone do not reveal the observed response outcomes.
What does a confidence interval communicate?
In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified method. For a response proportion, it can show how uncertain the estimated proportion is given the number of participants and observed responses. A small analysis population usually yields limited precision, but no interval can be reconstructed without the underlying endpoint counts and an analysis method. The registry record reports neither a response estimate nor a confidence interval.
A confidence interval is not a guarantee that the true value lies within its limits, and it does not by itself establish whether an effect is clinically meaningful. In a single-group trial, an interval around a response proportion would still describe uncertainty in that group's outcome; it would not create a comparison with another treatment. No confidence interval or comparative effect is reported for the primary endpoint.
What does the design permit?
In general, a single-group trial can describe outcomes among participants who received the study treatment. It cannot estimate a randomized between-group contrast because there is no control group. This trial is described as single-group, open-label, with allocation not applicable. The primary endpoint description includes assessment by a blinded independent review committee, but that does not change the one-group design. The registry record does not report a randomized comparison or another control condition.
Open-label means masking was absent. In general, knowledge of treatment assignment can influence some parts of trial conduct or assessment. Independent review can be used to add a separate assessment of response, but the registry record does not specify the committee's procedures, whether adjudication occurred, or how disagreements were handled. It is therefore possible to describe the planned independent assessment, but not to evaluate its implementation from the record.
How should planning illustrations be read?
In general, sample-size planning uses assumptions about the target effect, significance level, allocation, and statistical method to estimate the number of participants needed for a study design. The planning illustration associated with the analysis is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it states that the effect to detect is a specified fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it expresses participants per arm.
Those assumptions describe an illustration and are not the trial's own design: this study had one treatment group, not two equally allocated arms. The registry record does not report the trial's sample-size justification. Planning numbers, where shown, are not observed power, do not change the number enrolled, and cannot substitute for trial results. In particular, a planning calculation does not supply the missing primary endpoint estimate.
Why do analysis populations matter?
In general, an analysis population defines which participants contribute to a particular outcome estimate. Enrollment, treatment exposure, evaluability, and membership in a biomarker subgroup are not interchangeable. The registry reports five enrolled and three evaluable, and the primary endpoint applies to WT EZH2 status. It does not report a complete participant disposition or the size of the primary endpoint analysis population. The relationship between the five enrolled participants, three evaluable participants, and the WT subgroup is therefore not fully described.
Missing outcome data can affect interpretation when participants do not have an evaluable assessment. General approaches include defining a primary analysis population in advance and specifying how missing assessments are handled. These details are not reported in the registry record. With no individual participant outcomes, it is not possible to assess the reasons for non-evaluability, apply alternative missing-data assumptions, or evaluate the sensitivity of an endpoint estimate to those assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary objective response rate and several secondary outcomes: progression-free survival, duration of response, objective response rate in a subset with mutant EZH2 status, and objective response rate in rituximab-refractory participants. Testing or estimating multiple outcomes can raise multiplicity concerns in general, because repeated statistical tests may increase the chance of at least one apparently notable result. The registry record does not report a multiplicity strategy, hierarchy among secondary outcomes, or adjustment procedure. It also reports no analyses for these outcomes in the information available.
The record states that only three of five enrolled participants were evaluable, but does not describe the reasons for non-evaluability or give a complete analysis-population breakdown. The primary endpoint concerns participants with WT EZH2 status, and the record does not state how many evaluable participants belonged to that subgroup. Handling of missing endpoint assessments, any imputation method, and sensitivity analyses are not reported in the registry record.
These omissions matter because an endpoint estimate depends on who is included and how unavailable assessments are treated. They also limit interpretation of subgroup outcomes: the record names a mutant EZH2 subgroup analysis but does not provide its size or results. With no participant-level data or summary statistics, the reported enrollment and evaluability counts cannot be used to recover the missing outcomes or determine whether missingness affected the findings.
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 |
|---|---|---|---|
| Tazmetostat in Combination With Rituximab | 1 | 5 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tazmetostat in Combination With Rituximab | 0 of 5 |
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 |
|---|---|
| Tazmetostat in Combination With Rituximab | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Tazmetostat in Combination With Rituximab |
|---|---|---|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 5 |
| Cardiac failure acute | Cardiac disorders | 1 of 5 |
| Myocardial infarction | Cardiac disorders | 1 of 5 |
| Abdominal pain | Gastrointestinal disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tazmetostat in Combination With Rituximab |
|---|---|---|
| Infusion related reaction | Injury, poisoning and procedural complications | 2 of 5 |
| Blood creatinine increased | Investigations | 2 of 5 |
| Urticaria | Skin and subcutaneous tissue disorders | 1 of 5 |
| Insomnia | Psychiatric disorders | 1 of 5 |
| Cardiomegaly | Cardiac disorders | 1 of 5 |
| Ear pain | Ear and labyrinth disorders | 1 of 5 |
| Foreign body sensation in eyes | Eye disorders | 1 of 5 |
| Headache | Nervous system disorders | 1 of 5 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Contusion | Injury, poisoning and procedural complications | 1 of 5 |
Serious events with the highest arm-level rate: gastrointestinal haemorrhage (20.0%), cardiac failure acute (20.0%), myocardial infarction (20.0%), abdominal pain (20.0%).
For the treatment group, the registry reports five participants at risk for serious adverse events and one affected. It reports five participants at risk for other adverse events and five affected. The death count is zero. These figures describe events recorded in the trial group; they do not establish whether an event was caused by tazemetostat, rituximab, the combination, or another factor.
The listed serious adverse event terms are gastrointestinal haemorrhage, cardiac failure acute, myocardial infarction, and abdominal pain, each reported as 20.0%. The registry record does not provide additional event-level details or clarify whether terms could occur in the same participant. The percentages should therefore be read as reported, not as evidence that the listed events occurred in distinct participants.
Safety counts from a group of five participants are descriptive and offer limited information about the range or frequency of uncommon events. The record does not report event timing, severity grades, duration, relatedness assessments, or participant-level overlap for these terms. Absence of a reported death in this group does not resolve those other uncertainties.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase II, open-label, single-group study of tazemetostat with rituximab in relapsed or refractory follicular lymphoma. It reports five participants enrolled, three evaluable, and early termination for business reasons. It also records the primary endpoint definition, planned assessment times, and a limited set of safety counts. Those details describe the study and the extent of its posted results.
The primary endpoint was objective response rate for participants with WT EZH2 status, based on complete or partial response. However, the registry reports no summary statistics for this endpoint and does not present individual participant data. It is not possible from the record to state the response rate, its precision, or the number of participants in the endpoint population. The listed secondary outcomes also do not have results reported in the available record.
The study's one-group design does not provide a randomized treatment comparison. Even a reported response proportion would describe outcomes in this group, not the difference between the combination and another treatment. In this record, the primary estimate is absent as well, so the available information does not quantify response or comparative effect.
The safety counts indicate that one participant had a serious adverse event, all five had other adverse events, and no deaths were reported in the group. The serious event terms and percentages are descriptive. They cannot by themselves establish causation or characterize the broader safety profile.
Accordingly, the posted record supports a narrow reading: a small study was terminated early, few participants were evaluable, and endpoint summary statistics are unavailable. It does not support a conclusion about treatment efficacy, comparative benefit, or the frequency of outcomes in a broader population.
13. Why This Trial Matters Statistically
This trial illustrates why design and reporting context are essential to statistical interpretation. A named endpoint and an assessment schedule do not amount to an outcome estimate. Objective response rate was defined and planned for assessment, but the registry reports no summary statistics. Readers therefore need to distinguish an endpoint that was intended to be measured from a result that can actually be interpreted.
The difference between enrollment and evaluability is also important. Five participants enrolled, while three were evaluable; the primary endpoint was restricted to the WT EZH2 population, whose size is not reported. That chain of populations matters for understanding what denominator an endpoint would use. Without the subgroup size, response counts, or participant-level records, the endpoint cannot be reconstructed.
The single-group design offers no randomized comparator. Statistical descriptions of a treatment group cannot provide the same information as a between-group comparison, because there is no concurrent control to estimate a contrast. The design and early termination constrain what can be learned, independently of the endpoint's clinical importance.
Safety reporting shows another statistical issue: percentages and counts in a very small group can be highly sensitive to the experience of individual participants. The registry's adverse event figures should be read as descriptive records, not as stable estimates of event frequency or evidence of causation.
Finally, planning illustrations and observed results answer different questions. Sample-size scenarios describe what might be needed under specified assumptions; they are not observed power and do not fill gaps in trial outcomes. Here, no primary endpoint estimate is reported, and the registry does not state the trial's own sample-size justification. Keeping those distinctions clear prevents a study's intended methods from being mistaken for evidence about its outcomes.
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 most direct limitation is the absence of primary endpoint summary statistics. The record states that the study ended early for business reasons, with five participants enrolled and only three evaluable; it does not provide response counts, an objective response rate, or individual participant data. The reason for early termination is characterized as business-related, but further details are not reported in the registry record.
The primary endpoint applied to participants with WT EZH2 status, yet the record does not report the number of evaluable participants in that subgroup. It also does not give results for the listed secondary endpoints. Thus, the available record cannot describe response by EZH2 subgroup, response duration, or progression-free survival.
The single-group, open-label design has no randomized control arm, limiting comparative interpretation. The planned blinded independent review committee assessment is noted, but review procedures are not reported. The registry also does not report a complete statistical analysis plan, multiplicity approach, missing-data methods, or the reasons participants were not evaluable.
Safety information is similarly limited by the small group and lack of event-level detail. The record reports counts and selected serious event terms, but does not give event timing, relatedness, severity grades, or participant-level overlap. These limitations prevent a fuller assessment of the clinical and statistical meaning of the posted safety data.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma — NCT04762160.
- Registry record last updated 2024-03-25; status last verified 2024-03.
- Results first posted 2023-11-21.
- 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
SYMPHONY-II was a phase II, open-label, multicenter, single-group trial of tazemetostat with rituximab for relapsed or refractory follicular lymphoma. The registry lists five participants enrolled and states that the study was terminated early for business reasons; three participants were evaluable.
The primary endpoint was objective response rate in participants with WT EZH2 status, using complete or partial response under the 2014 Lugano Classification and planned assessments during Cycles 3, 6, 12, 18, and 24. No primary endpoint summary statistics or individual participant data are reported. The record lists progression-free survival, duration of response, and additional subgroup response outcomes, without results in the available information.
For safety, the record reports one serious adverse event among five participants at risk, other adverse events in five of five, and zero deaths. The single-group design and missing endpoint results preclude a comparative efficacy estimate.