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 Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma (NCT00743288), a na phase 1, phase 2 study. The primary outcome is Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00743288 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oncotherapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Patients with recurrent multiple myeloma; the official title describes the population as having relapsed or refractory multiple myeloma. Further eligibility details and the characteristics of enrolled participants are not reported in the registry record.
Intervention
Oral melphalan combined with oral panobinostat, also called LBH589 in the registry record. The record describes an initial schedule and a change following toxicity, but the later schedule description is incomplete.
Comparator
There is no separate comparator group listed. The study is identified as single group, with allocation listed as NA and masking as none.
Primary question
The listed primary outcome concerns overall response rate and clinical benefit rate after treatment. The registry record does not report numerical results for either measure, so the magnitude and precision of response cannot be assessed.
In practical terms, this Phase I/II study was designed to examine a combination of two drugs in patients with recurrent or relapsed or refractory multiple myeloma. The registry summary describes the purpose as studying side effects and the best dose of melphalan when given with panobinostat. The primary outcome listing focuses on response categories: complete response, very good partial response, partial response, and minimal response. Overall response rate combines the first three categories, while clinical benefit rate also includes minimal response.
The registry record lists 40 participants and a 24 months timeframe for the primary outcome. It does not include the number of participants in each response category, an overall response estimate, a clinical benefit estimate, or uncertainty estimates. The question can therefore be described from the outcome definition, but the posted record does not allow a reader to quantify the response observed in this group or judge its precision. The study has no randomized control group, so it is not a direct comparison of the combination with another treatment or with no treatment.
3. Trial Design
This is a completed Phase I/II study with a single-group model. The registry record lists 40 participants, no masking, and allocation as NA. There is no separate control arm listed, and the record itself flags that the study is not a randomized comparison. The sponsor is Oncotherapeutics. The listed start is 2008-07, and the primary completion is 2012-11.
The intervention group is named Melphalan and Panobinostat. The registry describes Schedule A as 10mg/daily of LBH589 by mouth on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle, with melphalan by mouth at 0.05 mg/kg on days 1-5 of week 1. It then says toxicity led to changes in dose and schedule, and begins a Schedule B1 description. That description ends after the melphalan dose entry and does not give the rest of the schedule. The complete treatment schedule and how many participants received each schedule are not reported in the registry record.
The registry summary says the study examined side effects and the best dose of melphalan combined with panobinostat. The design label includes both Phase I and Phase II, but details of dose escalation, dose selection, and the transition between phases are not reported in the registry record. Nor is the rationale for the enrollment target reported. These omissions mean the design can be summarized at a broad level, but the specific conduct of dose-finding and the basis for the planned enrollment cannot be reconstructed from this record.
Secondary outcomes listed are duration of response and time to progression. Their operational definitions, analysis details, and reported results are not reported in the registry record. The absence of a control arm is central when interpreting any outcome: the study can describe what was recorded among participants receiving the combination, but it cannot isolate a treatment effect relative to a concurrent comparison group.
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.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Melphalan and Panobinostat Schedule A | Melphalan and Panobinostat Schedule B1 | Melphalan and Panobinostat Schedule B2 | Melphalan and Panobinostat Schedule C | Melphalan and Panobinostat Schedule D1 | Melphalan and Panobinostat Schedule D2 |
|---|---|---|---|---|---|---|
| STARTED | 3 | 3 | 6 | 7 | 6 | 6 |
| COMPLETED | 0 | 0 | 1 | 0 | 0 | 1 |
| NOT COMPLETED | 3 | 3 | 5 | 7 | 6 | 5 |
Reasons for not completing this period:
| Reason | Melphalan and Panobinostat Schedule A | Melphalan and Panobinostat Schedule B1 | Melphalan and Panobinostat Schedule B2 | Melphalan and Panobinostat Schedule C | Melphalan and Panobinostat Schedule D1 | Melphalan and Panobinostat Schedule D2 |
|---|---|---|---|---|---|---|
| Adverse Event | 1 | 1 | 2 | 2 | 1 | 1 |
| Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 |
| Progressive disease (PD) | 2 | 0 | 1 | 4 | 5 | 3 |
| Worsening of condition (Not PD) | 0 | 2 | 1 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: MTD for Melphalan and Panobinostat was reached in the cohort of 6 participants who received 20 mg/daily LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1 of each cycle. Three additional patients were enrolled as part of the phase 2 expansion.
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 | Melphalan and Panobinostat (LBH589) |
|---|---|---|
| Participants analysed | 40 | |
| Age, Continuous | years | 65.4 (34.2 to 88.2) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 25 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 32 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | participants | 40 |
| Prior regimens: Number of prior regimens | number of prior regimens | 4 (1 to 16) |
| Prior regimens: Number of Bortezomib-containing prior regimens | number of prior regimens | 2 (0 to 9) |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled as overall response rate and clinical benefit rate following treatment with panobinostat and melphalan. Overall response rate is defined as complete response plus very good partial response plus partial response. Clinical benefit rate adds minimal response to those categories. The registry record says responses were evaluated using criteria modified from those developed by Blade and colleagues, with baseline as the reference point for evaluating response improvement. It also says that this baseline reference applies when a participant has already achieved a response and then moves to a better response grade.
These measures summarize response as categories rather than as a continuous measurement. In general, a response rate is useful for describing how many people in a study meet a defined response threshold. Including minimal response in clinical benefit rate makes that measure broader than overall response rate, according to the definitions in this record. Neither measure, on its own, describes how long a response lasts; duration of response is listed separately as a secondary outcome.
The primary outcome timeframe is 24 months. The registry record does not report the number or proportion of participants in any response category, nor does it give a confidence interval or other precision estimate. Thus the endpoint definition is available, but the numerical response findings are not. The criteria are described as modified, and further detail about the modifications is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this completed study enrolled 40 participants into a single group receiving melphalan and panobinostat. It defines the primary response outcomes and gives a 24 months timeframe. It does not report numerical overall response rate or clinical benefit rate results, so there is no posted estimate to interpret as the observed frequency of response. The record also does not give confidence intervals, standard errors, or another measure of precision for those outcomes.
That distinction matters. An outcome definition tells readers what investigators intended to count, while an outcome result tells readers what was counted. The former is present; the latter is not. It would be inappropriate to infer response counts from the enrollment total, from the treatment description, or from the safety data. In particular, the registry’s statement that the study is completed does not itself establish what the response findings were.
The absence of a separate comparator group further limits interpretation. In a single-group study, response and safety outcomes describe participants observed under the study treatment and procedures. Without a randomized comparison, differences from another treatment, usual care, or the natural course of disease cannot be estimated from this design. General statistical interpretation: a comparison group helps distinguish changes associated with an intervention from other influences, but this registry record does not describe such a group.
The registry lists duration of response and time to progression as secondary outcomes, but does not report their results or analysis details. These outcomes would address different questions from response rate: response duration concerns how long a response persists, while time to progression concerns timing until progression. Their definitions, event counts, and estimates are not reported in the registry record, so no conclusion about those outcomes can be drawn from the listed titles alone.
The available safety entries show that 7 of 40 participants were recorded as having a serious adverse event, and 22 of 40 as having another adverse event. These counts describe the entries in the registry; they do not establish how frequently similar events would occur in another population or under another treatment. The record names several serious adverse event terms at 2.5% each, but does not provide enough detail to assess timing, severity grades, attribution, or overlap among events. Deaths are not reported in the registry record.
Overall, the posted information supports a description of the study’s design, stated endpoints, treatment schedule as far as recorded, and adverse-event counts. It does not support a numerical assessment of response, a comparison of efficacy, or a precise account of uncertainty. Those gaps should remain visible rather than be filled by assumptions about what a Phase I/II study usually reports.
9. Statistical Methods Explained
The registry identifies a single-group Phase I/II design, with no masking and allocation listed as NA. It does not provide a detailed statistical analysis plan. In particular, the statistical methods for response outcomes, the methods for time-to-event outcomes, any planned covariate adjustment, and any inferential testing are not reported in the registry record. The statistical discussion below therefore explains the outcome types generally and separates those explanations from what can be confirmed about this study.
What does a response rate represent?
General: a binary outcome classifies each participant into one of two states for a specified definition, such as meeting or not meeting a response criterion. A response rate summarizes the share of participants who meet the defined criterion. Here, the record defines overall response rate using complete response, very good partial response, and partial response; clinical benefit rate also includes minimal response. The record does not report the counts in those categories or the calculated rates. Because the categories are defined relative to baseline, the stated response classification depends on the baseline reference described in the registry.
A rate is only interpretable alongside its denominator and the rules used to classify participants. The record lists 40 enrolled participants, but does not state the response-analysis population or how participants without an evaluable response were handled. It is therefore not possible to confirm from the posted information whether the enrolled total was also the denominator for each response calculation. The criteria are described as modified from those developed by Blade and colleagues, but the exact modifications are not reported in the registry record.
How should precision be understood?
General: an estimate from a study is subject to sampling variability. A confidence interval expresses a range of values compatible with the data under a specified statistical procedure; it is not a guarantee that the true value lies in that range. A narrower interval usually indicates greater precision, while a wider interval indicates less precision. No confidence interval or other uncertainty measure for the primary response outcomes is reported in the registry record. Without both a result and its precision, readers cannot tell how much uncertainty surrounds the response estimate.
General: statistical significance and clinical importance are different ideas. A p-value, when reported, addresses compatibility of data with a specified statistical model and null hypothesis; it does not by itself measure the size or importance of an effect. The registry record does not report a p-value or a hypothesis test for the primary outcomes. Since there is no comparator group listed, the record also does not establish a treatment contrast for a between-group test.
What is different about time-to-event outcomes?
General: time-to-event analyses consider both when an event occurs and whether a participant’s event time is observed during follow-up. Participants without an observed event may be censored, meaning their available follow-up contributes information up to a point without establishing a later event time. Methods for these outcomes need to address such incomplete observation. Duration of response and time to progression are listed as secondary outcomes here, but their event definitions, censoring rules, follow-up details, analytic methods, and results are not reported in the registry record. No survival curve or time-to-event estimate should be inferred from the outcome names alone.
General: over-dispersion is relevant when count data vary more than a chosen statistical model expects. A model that ignores this extra variability can understate uncertainty. This registry record does not describe a count outcome model or a dispersion assessment, and over-dispersion is not indicated as a method used in the analysis. It is therefore a general methodological consideration, not a finding about this study.
What does the sample-size section mean?
The accompanying sample-size section is a planning illustration, not a record of the study’s original design calculation. Its stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; for other outcomes, it is participants per arm. This setup is distinct from the registry’s single-group design and should not be read as evidence that the trial randomized participants or included a control arm.
General: a planning illustration estimates how much information a hypothetical design might need under its assumptions. Such an illustration is not observed power and cannot substitute for a study’s actual analysis. The registry record does not report the trial’s own sample-size justification, the assumptions used in any original calculation, or whether the planned enrollment was changed. No numerical sample-size estimates are stated in this narrative because none are present in the registry record.
The registry lists five outcome measures and no analysis entries. That does not reveal what statistical procedures may have been used outside the registry; it means those procedures are not described in the posted record. Readers should distinguish the analysis plan, which is not reported, from the outcome definitions and safety counts that are reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome covering overall response rate and clinical benefit rate, and lists duration of response and time to progression as secondary outcomes. It also indicates five outcome measures in total. The method used to handle multiple outcomes or multiple response comparisons is not reported in the registry record. No hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses is described.
General: when several outcomes or tests are considered, the chance of at least one apparently notable result can increase if each is interpreted independently. A prespecified hierarchy or multiplicity adjustment can help clarify how evidence across outcomes should be interpreted. This is a general concern, not a claim that a particular procedure was or was not used outside the information in the registry.
Missing-data handling is also not reported in the registry record. The record does not state how participants who withdrew, lacked an evaluable response, or had incomplete follow-up were treated in the response or time-to-event analyses. It does not describe imputation, censoring rules, or sensitivity analyses. The analysis populations are not reported, so readers cannot determine whether reported outcomes, if available elsewhere, would use all enrolled participants or a defined subset.
These are important omissions because the response denominator and follow-up completeness can affect interpretation. They do not establish that data were missing or that an analysis was biased; they mean the registry record does not explain how such issues were addressed. The record also lists no analysis entries, so it does not provide statistical output with which to assess multiplicity, missingness, or population definitions.
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 |
|---|---|---|---|
| Melphalan and Panobinostat | 7 | 40 | 17.5% |
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 |
|---|---|
| Melphalan and Panobinostat | 22 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Melphalan and Panobinostat |
|---|---|---|
| Vertebral compression fracture | Injury, poisoning and procedural complications | 1 of 40 |
| Sepsis | Infections and infestations | 1 of 40 |
| Gram-negative sepsis | Infections and infestations | 1 of 40 |
| Deep vein thrombosis with oulmonary embolism | Vascular disorders | 1 of 40 |
| Altered mental status | Psychiatric disorders | 1 of 40 |
| Hypecalcemia | Metabolism and nutrition disorders | 1 of 40 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 40 |
| Hyponatremia | Metabolism and nutrition disorders | 1 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Melphalan and Panobinostat |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 11 of 40 |
| Thrombocytopenia | Blood and lymphatic system disorders | 10 of 40 |
| Lymphopenia | Blood and lymphatic system disorders | 9 of 40 |
| Anemia (>=grade 3) | Blood and lymphatic system disorders | 6 of 40 |
| Leukopenia | Blood and lymphatic system disorders | 6 of 40 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 40 |
Serious events with the highest arm-level rate: vertebral compression fracture (2.5%), sepsis (2.5%), gram-negative sepsis (2.5%), deep vein thrombosis with oulmonary embolism (2.5%), altered mental status (2.5%).
The safety listing is for the Melphalan and Panobinostat group, with 40 participants at risk for both serious and other adverse events. It records 7 participants with a serious adverse event and 22 with another adverse event. These are participant counts, not counts of every individual event. The record does not say whether a participant could be represented in both categories, so the counts should not be added together or treated as mutually exclusive groups.
The listed serious adverse event terms include Vertebral compression fracture, Sepsis, Gram-negative sepsis, Deep vein thrombosis with oulmonary embolism, Altered mental status, and Hypecalcemia. Each is listed at 2.5%. The registry gives no further detail on event timing, severity grade, duration, attribution, or the number of events per affected participant. The terms should be read as registry labels; the record does not provide enough context to interpret their clinical circumstances.
Deaths are not reported in the registry record. This is not evidence that there were no deaths. The safety counts describe what the record reports for this study group and do not establish comparative risk, because there is no comparator group listed.
12. What the Result Does, and Does Not, Mean
The result of a registry review is not always a treatment-effect estimate. In this case, the record provides the study design, the intended response definitions, a timeframe, and adverse-event counts. It does not provide numerical results for overall response rate, clinical benefit rate, duration of response, or time to progression. Consequently, the magnitude of response and its statistical precision cannot be evaluated from this record.
The distinction between “not reported” and “not observed” is essential. The absence of a numerical response result does not mean that no responses occurred. Likewise, the absence of a death count does not mean that no deaths occurred. It means the registry record does not report those results. The listed safety counts can be described as recorded, but cannot fill in the missing efficacy results.
The single-group design also sets a limit on what the study can show. It can describe outcomes among participants treated with the combination, but it does not provide a randomized comparison against another treatment. General: in the absence of a concurrent comparator, outcomes may reflect multiple influences, and a within-group observation does not isolate the contribution of one component of a combination. The registry provides no basis for attributing an outcome specifically to melphalan, panobinostat, or their combination.
The enrollment of 40 participants and the 24 months primary-outcome timeframe describe the record’s scope; they do not by themselves establish precision, completeness of follow-up, or generalizability. The record does not report participant characteristics, analysis populations, missing-data methods, or the statistical analysis plan. Those details would be needed for a fuller assessment of how the findings were generated and to whom they might apply.
Accordingly, the most defensible reading is descriptive: this was a completed, single-group Phase I/II study of the combination, with response and safety outcomes specified in the registry. The posted record does not supply enough numerical outcome information to assess response or compare the combination with another approach.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a clearly named endpoint and a reported result. The registry defines overall response rate and clinical benefit rate, including the response categories used for each, but does not give their observed values. An endpoint definition is necessary for interpretation, yet it cannot answer how many participants met that definition. This distinction is useful when reading registry records: outcome titles and completed status should not be mistaken for numerical findings.
The design also illustrates why study structure affects the question that can be answered. A single-group study can document outcomes within the treated group. It cannot provide a randomized estimate of how outcomes differ from a comparator group that is not present. This is not a flaw that can be corrected by a statistical calculation after the fact; the design determines which comparisons the data can support.
The registry’s safety entries show another important distinction: participant counts with events are not necessarily counts of individual events, and counts alone do not describe timing, severity, or attribution. The serious adverse event terms and their listed percentages provide a limited summary, while leaving those contextual details unreported.
Finally, the sample-size section is a planning illustration and not the trial’s original design rationale or observed power. Its hypothetical two-arm assumptions differ from the listed single-group structure. Keeping planning exercises separate from actual design and analysis helps prevent readers from treating a hypothetical calculation as evidence about how the trial was conducted or what it found.
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 consequential limitation of the registry record is that it does not report numerical results for the primary response outcomes. It also does not report results for the listed secondary outcomes. No estimate of response, confidence interval, or other measure of precision is available. The completed status cannot substitute for those missing results.
The study has a single group and no randomized comparator listed. Therefore, any outcomes recorded within the group cannot be interpreted as a comparative treatment effect from this design. The record also does not report participant characteristics, eligibility criteria in detail, or the analysis population. The enrollment total alone cannot show whether all participants were evaluable for each outcome.
The treatment description is incomplete. Schedule A is described, and the record says toxicity led to changes in dose and schedule, but the Schedule B1 description is cut off. The record does not state how participants were assigned to schedules, how many received each schedule, or how dose decisions were made. These details limit interpretation of both exposure and safety.
Additional methods are not reported in the registry record: the trial’s own sample-size justification, the statistical analysis plan, handling of missing data, methods for the secondary time-to-event outcomes, and any multiplicity approach. The serious adverse event summary lacks further detail on severity, timing, attribution, and overlap, and deaths are not reported. These are limitations of the information available in the registry record; they do not establish that the study itself failed to collect or analyze those details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma — NCT00743288.
- Registry record last updated 2014-05-08; status last verified 2014-04.
- Results first posted 2014-04-25.
- 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 Phase I/II study enrolled 40 participants with recurrent multiple myeloma and evaluated oral melphalan with panobinostat. The registry identifies a single-group design, no masking, and allocation as NA. It lists a primary outcome of overall response rate and clinical benefit rate, with a 24 months timeframe, and secondary outcomes of duration of response and time to progression.
The record defines the response categories but does not report numerical primary or secondary outcome results. It records 7 participants with serious adverse events and 22 with other adverse events, among 40 at risk in each category. Deaths are not reported in the registry record. The full changed treatment schedule, statistical analysis plan, missing-data methods, and analysis populations are also not reported. The study can therefore be described from its design and listed safety entries, but the posted record does not support a numerical assessment of response or a comparative treatment effect.