ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma (NCT02757326), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose.

2. Clinical Question

3. Trial Design

This was a Phase Ib/II safety and efficacy study of single-agent opaganib in refractory or relapsed multiple myeloma. The record identifies the study model as sequential, with no masking and no randomized allocation. The planned Phase Ib dose-escalation levels were 250, 500, and 750 mg twice daily. The brief summary says dose finding was to use a Bayesian model averaging continual reassessment method. It describes a planned 18 patients for determining the maximum tolerated dose and up to 56 additional patients for the Phase II portion, at the maximum tolerated dose or the maximum dose used in Phase I.

The registry lists enrollment of 13 and reports the study status as terminated. The recorded start date is 2016-12-13, and primary completion is listed as 2019-05. These entries describe the study record; they do not explain why the study was terminated or how many participants entered each planned phase. Those details are not reported in the registry record.

Opaganib was administered orally. The arm description specifies continuous dosing and fasting conditions, with one treatment cycle defined as 28 days. The remaining Phase II arm description is incomplete in the registry record, so further details of that phase should not be inferred. The record also describes pharmacokinetic and pharmacodynamic assessments on Day 1 of Cycle 1, bone marrow biopsies before treatment and at the end of cycle #3 and cycle #6, and laboratory and biomarker assessments.

The design is primarily dose-finding rather than a controlled comparison of treatments. Dose cohorts are sequential, and the record does not identify a randomized control group. Differences among their observed safety figures cannot therefore be read as causal dose effects without further design and analysis information.

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

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.

Population: Patients with Refractory or Relapsed Multiple Myeloma Who have Previously Been Treated with Proteasome Inhibitors and Immunomodulatory Agents were treated with three doses of ABC294640.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose, measured over 6 months.

The primary outcome is maximum tolerated dose, measured in mg, with a stated timeframe of 6 months and a safety population. The registry describes evaluation of 250 mg, 500 mg, and 750 mg twice daily, using dose-limiting toxicity (DLT) and a Bayesian model averaging continual reassessment method. The selected dose is defined as the dose whose estimated probability of toxicity is closest to the target probability of 0.33 among the evaluated doses.

In general, a dose-finding endpoint is used to guide which dose is carried forward for further study, rather than to estimate comparative treatment benefit. DLT information helps characterize tolerability at the tested dose levels. A target toxicity probability makes the dose-selection objective explicit: the method seeks the evaluated dose whose estimated toxicity probability is nearest the target. The registry record does not report the estimated toxicity probabilities, the selected maximum tolerated dose, or a numerical primary outcome result. It therefore does not permit readers to identify which dose, if any, met the stated selection rule.

The outcome description names a method and a decision criterion, but does not report details such as the operational definition of DLT or how observations were handled in the final dose estimate. Those details are not reported in the registry record. The outcome title alone should not be mistaken for a posted finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a sequential dose-finding design mean?

In general, a sequential dose-finding study assigns or treats participants in stages rather than comparing all dose groups through random allocation. Information from earlier participants can inform decisions about later dose levels. The registry identifies the model as sequential and describes Bayesian model averaging continual reassessment for dose finding. It does not report the actual sequence of dose assignments, the decision rules used during conduct, or whether and how the method was modified in practice. Those details are not reported in the registry record.

A dose-finding objective differs from a conventional efficacy comparison. Here, the stated primary endpoint asks which tested dose has an estimated toxicity probability closest to a target of 0.33. That target is part of the endpoint definition; it is not a reported toxicity rate. The registry does not provide the dose-specific estimates or the final dose-selection result.

What does Bayesian model averaging continual reassessment mean?

In general, a continual reassessment method uses accumulated dose-toxicity information to update estimates of toxicity at the doses under study. Bayesian methods represent uncertainty in those estimates through probability distributions. Model averaging can account for uncertainty among candidate dose-toxicity models by combining their implications rather than relying on a single model. This general description explains the method named in the record; the specific candidate models, prior distributions, and updating rules are not reported in the registry record. It is not possible to reconstruct the dose-selection calculation from the posted information.

The target probability provides a reference for selecting among evaluated doses. A dose with an estimated probability near the target would be favored under the stated rule over a dose whose estimate is farther away, subject to the method’s implementation. The record does not say whether any dose estimate was near the target or whether a dose was selected. Thus the methodological description should not be read as evidence that the planned procedure produced a particular result.

How should the safety counts be interpreted?

In general, counts of participants affected describe how many people in a group had a reported event under the registry’s event definitions. The listed at-risk count gives the group size used for those safety entries. The serious adverse event counts are descriptive and are not adjusted estimates of comparative risk. They do not account, on their own, for differences in cohort size, time at risk, participant characteristics, or sequential assignment. Such details and any adjusted comparison are not reported in the registry record.

Serious adverse events and other adverse events are separate categories in the reported group data. A count of affected participants is not a measure of event severity beyond the category assigned in the record, and the counts do not establish that opaganib caused the event. The record lists term percentages separately, but does not make clear whether terms overlap or how they map to dose cohorts. Those percentages should not be combined or treated as mutually exclusive without that information.

What can a confidence interval tell a reader?

In general, a confidence interval describes the precision of an estimated quantity under a statistical model and a specified procedure. A narrower interval usually indicates greater precision than a wider interval, while neither an interval nor a point estimate resolves issues such as bias, confounding, or limitations of the design. No confidence interval for the primary dose estimate or a comparative efficacy effect is reported in the registry record. There is therefore no interval-based precision assessment to interpret for those outcomes.

What is not available for checking the analysis?

The record lists no posted analyses. It also does not report the detailed statistical analysis plan, the precise DLT definition, model specifications, handling of missing observations, or the analysis populations for secondary outcomes. The primary outcome identifies a safety population, but further population definitions are not reported. These omissions limit independent assessment of how the planned methods were implemented and how robust any dose-selection result would be. Since a numerical primary result is absent, a recalculation from posted summary statistics is not possible.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary dose-finding outcome and several secondary outcome descriptions, including antitumor activity after 3 cycles of treatment, participants with dose-limiting toxicity, and maximum concentration (Cmax) of ABC294640. Four outcome measures are listed in total. No analyses are posted, and the registry record does not report a plan for handling multiplicity across outcomes, time points, or dose groups. It is therefore not possible to determine whether any adjustment was planned or applied, or how the outcomes were prioritized beyond the primary designation.

The primary outcome description specifies a safety population, but further detail about the population used for each analysis is not reported in the registry record. The record does not provide numbers analyzed for the outcomes or explain how participants with incomplete observations were handled. Missing-data methods, reasons for missing observations, and any sensitivity analyses are not reported. These omissions matter because the available observations and analysis population can affect estimates, especially in a small, sequential dose-finding study.

The study status is terminated, and enrollment is listed as 13. The registry does not explain whether termination affected data collection, follow-up, or planned analyses. It also does not report interim analyses, stopping decisions for futility, or whether the planned Phase II stopping rules were implemented. The brief summary mentions interim stopping rules for futility as part of the planned Phase II design; the actual use and consequences of those rules are not reported in the registry record. As a result, neither multiplicity control nor missing-data handling can be evaluated from the posted information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: altered mental status (33.3%), pain (25.0%), depressed level of consciousness (25.0%), colitis (25.0%), constipation (25.0%).

The registry lists serious adverse event counts by Phase 1b dose group. At 250 mg, 3 participants were at risk and 1 was affected; at 500 mg, 4 were at risk and 3 were affected; at 750 mg, 6 were at risk and 1 was affected. The record lists 0 deaths in each group. Other adverse event counts are also reported separately, with all listed participants affected in each dose group. These are descriptive registry entries, not adjusted comparisons.

The serious-event terms listed include ALTERED MENTAL STATUS at 33.3%, and Pain, Depressed level of consciousness, Colitis, Constipation, and Hip fracture at 25.0% each. The registry record does not explain in this listing whether these percentages use a shared denominator, whether terms overlap, or how the terms are distributed across dose groups. The term percentages should not be added or interpreted as a partition of participants.

In general, adverse-event counts show what was recorded among participants under study conditions; they do not, by themselves, establish causation. The sequential, nonrandomized design and differing cohort sizes also mean these figures do not provide a like-for-like safety comparison among doses. Further information about exposure time, event definitions, and comparative analysis is not reported in the registry record.

12. What the Result Does, and Does Not, Mean

The record establishes that this was a Phase Ib/II, sequential study of single-agent opaganib for refractory or relapsed multiple myeloma, with planned dose escalation and a maximum tolerated dose endpoint. It also gives the intended dose-selection criterion: select the dose whose estimated toxicity probability is closest to 0.33 among the evaluated doses. These descriptions clarify the question the study was designed to address.

They do not establish the answer to that question. The registry does not report a selected maximum tolerated dose, dose-specific toxicity probabilities, or a numerical primary outcome result. Although a secondary outcome concerns antitumor activity after 3 cycles of treatment, no efficacy result is posted. The information therefore cannot establish whether opaganib had antitumor activity or whether any dose was effective. It also cannot establish that treatment did or did not benefit participants.

The adverse-event entries describe observed reports in the listed Phase 1b groups. They do not establish that the study drug caused those events, and they do not support a controlled comparison between doses. Cohorts were sequential and there was no randomized comparator. The registry’s listed serious-event terms also lack enough context to determine how the percentages relate to participant groups or whether terms overlap.

The planned enrollment figures in the brief summary are not outcome findings. The registry lists enrollment of 13 and status as terminated, but does not explain the termination or reconcile the recorded enrollment with the planned Phase Ib and Phase II numbers. Those entries should not be used to infer a reason for stopping, the amount of follow-up completed, or the completeness of outcome reporting.

In general, a registry record can describe study design and selected posted results, but the absence of a posted estimate leaves important uncertainty. For this study, no primary statistical result or analysis is available in the record. Interpretation should therefore remain limited to the design, planned methods, and descriptive safety figures that are reported.

13. Why This Trial Matters Statistically

This trial is statistically notable because it frames an early-phase study as dose finding rather than as a randomized comparison of treatments. The stated primary objective is to choose among three planned dose levels using dose-limiting toxicity and a Bayesian model averaging continual reassessment method. The target probability of toxicity, 0.33, makes the intended decision criterion explicit. This is a useful distinction: a dose-finding study asks which tested dose best fits a prespecified safety target, not whether one treatment is superior to a control.

The sequential design also makes the availability of method details especially relevant. In general, sequential decisions depend on how information from earlier participants influences later decisions. The registry names the method but does not report the model specifications, decision rules, or final dose estimates. Without those results and details, readers cannot assess the precision or stability of the dose-selection conclusion.

The record also illustrates why descriptive safety counts need design context. The reported groups differ in size and were not randomized. Their serious adverse event counts can be read as group-specific descriptions, but not as direct evidence that a dose causes more or fewer events than another dose. A causal or comparative interpretation would require design and analysis information beyond these entries.

Finally, the record distinguishes planned enrollment from recorded enrollment and planned outcomes from posted results. It lists enrollment of 13, while the summary describes larger planned cohorts. The status is terminated, but the reason and the primary endpoint result are not reported. These gaps are important when assessing how much evidence the registry record contributes. The study’s statistical purpose is clear; its reported results are not sufficient to establish a dose-selection finding or an 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.

The main limitation for interpretation is that the registry does not report the primary endpoint result. It names maximum tolerated dose as the primary outcome and describes a dose-selection method, but does not provide the selected dose, toxicity estimates, or a numerical result. No analyses are posted. The record therefore supports description of the planned method, not evaluation of its outcome.

Enrollment is listed as 13, whereas the brief summary describes planned enrollment of 18 patients for Phase Ib dose finding and up to 56 additional patients in Phase II. The registry does not explain how these planned numbers relate to actual conduct, whether all planned phases began, or how many participants contributed to each outcome. The status is terminated, but the reason is not reported in the registry record.

The study has no randomized comparator and is described as sequential. Consequently, the safety figures across dose groups are not like-for-like comparisons. The record does not provide exposure-adjusted rates, a comparative statistical analysis, or enough detail about participant characteristics and follow-up to assess potential differences across groups.

Important analytic details are also absent: the operational DLT definition, exact implementation of the dose-finding method, missing-data handling, analysis populations beyond the named safety population, and any multiplicity strategy. The serious adverse event term percentages are not accompanied by details that establish their denominators or whether terms overlap. The Phase II arm description is incomplete. These limitations constrain interpretation of both the planned study and the posted safety data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma — NCT02757326.
• Registry record last updated 2021-06-18; status last verified 2021-04.
• Results first posted 2021-06-18.
• 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.

18. Record Summary

The registry describes NCT02757326, a Phase Ib/II sequential study of opaganib in refractory or relapsed multiple myeloma after prior treatment with proteasome inhibitors and immunomodulatory drugs. The planned Phase Ib dose levels were 250, 500, and 750 mg twice daily. The primary objective was maximum tolerated dose, using dose-limiting toxicity and a Bayesian model averaging continual reassessment method with a target toxicity probability of 0.33.

Enrollment is listed as 13, and study status is terminated. The primary endpoint result and reason for termination are not reported in the registry record. Serious adverse event counts are listed by dose group, with 0 deaths recorded in each group; no randomized comparison is available. Four outcome measures are listed, but no analyses are posted. The record therefore describes the trial’s design and selected safety data without reporting a dose-selection result or an efficacy analysis.