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 Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis (NCT03303950), a na phase 2 study. The primary outcome is Non-relapse Mortality (NRM) at Day 100.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03303950 |
| Phase | Phase 2 |
| Condition | Anemia, ASXL1 Gene Mutation, EZH2 Gene Mutation |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with multiple myeloma or myelofibrosis. The registry record also lists related diagnoses and conditions, including plasma cell myeloma, primary and secondary myelofibrosis, recurrent plasma cell myeloma, anemia, thrombocytopenia, and several gene mutations. It does not report how the enrolled participants were distributed across these diagnoses or conditions, or provide further eligibility details in the record.
Intervention
The treatment combined busulfan and fludarabine before hematopoietic cell transplantation, followed by cyclophosphamide. The treatment description specifies intravenous busulfan over 2 hours and fludarabine over 30 minutes on days -5 to -2, transplantation on day 0, and intravenous cyclophosphamide over 60 minutes on days 3 and 4. Laboratory biomarker analysis is also listed as an intervention.
Comparator
There was no comparison group in the registered design. The study is described as single-group, with allocation marked NA and masking marked none. Consequently, the record does not provide a randomized or concurrent control group for estimating how outcomes differ between treatment strategies. The clinical question is not a direct comparison of this regimen with another regimen or with no treatment.
Primary question
The primary outcome was the count of participants experiencing non-relapse mortality up to day 100. The record defines this as death due to graft-versus-host disease, infections, sepsis, or organ toxicity involving the lung, liver, or kidney; death attributed to progression or relapse of the underlying disease is excluded. The observed primary outcome count is not reported in the registry record.
3. Trial Design
This is a phase II, single-group clinical study registered as NCT03303950. The study title concerns allogeneic stem cell transplantation for multiple myeloma and myelofibrosis. The official title describes busulfan, fludarabine, donor stem cell transplantation, and cyclophosphamide in participants with either condition. The University of Utah is listed as sponsor. The registry record reports enrollment of 6 and a status of terminated. The start date is 2018-03-30, and the primary completion date is 2019-05-14.
The treatment sequence is described in the arm information. Participants receive busulfan and fludarabine intravenously on days -5 to -2, undergo hematopoietic cell transplantation on day 0, and receive cyclophosphamide intravenously on days 3 and 4. The record also lists laboratory biomarker analysis. It does not report a separate treatment arm or a control condition.
Allocation is marked NA, masking is marked none, and the model is single-group. These design features mean the study record does not describe random assignment between treatment strategies or blinding. The treatment group’s outcomes can be described, but a within-trial contrast against a control group is not available. A comparison with external or historical outcomes would require information and assumptions not reported in the registry record.
The primary outcome is non-relapse mortality up to day 100, expressed as a count of participants. Secondary outcomes include non-relapse mortality at day 365, acute and chronic graft-versus-host disease, overall and disease-free survival at one year, clinical responses, and minimal residual disease response. The registry record lists 8 outcome measures and 0 analyses. The posted information does not describe the statistical analysis plan, the reason for termination, or the number of enrolled participants with each underlying disease.
The enrollment figure and design should be read as features of the registered study, not as evidence of a treatment effect. With no control group, any outcome describes participants in the treatment group and cannot by itself establish how those outcomes compare with another approach. The record does not report whether the planned enrollment was reached or provide a reason for the terminated status.
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
| Stage | All Particpants - Treatment |
|---|---|
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
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 | All Participants - Treatment |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 56.17 (SD 6.97) |
| Age, Continuous | years | 54.5 (50 to 69) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Non-relapse Mortality (NRM) at Day 100, measured over Up to day 100.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is non-relapse mortality (NRM) up to day 100, measured as the count of participants. The registry definition classifies deaths due to graft-versus-host disease, infections, sepsis, or organ toxicity involving the lung, liver, or kidney as NRM. Death attributed to the underlying disease, including progression or relapse, is not counted as NRM. This distinction separates deaths attributed to treatment-related complications from deaths attributed to disease in the endpoint definition; the registry record does not report how individual deaths, if any, were adjudicated.
In general, NRM is used in transplant studies to describe mortality that is not attributed to relapse or progression of the underlying disease. It can therefore focus attention on a different outcome from overall mortality. The choice of endpoint also makes cause-of-death classification important: an event’s inclusion depends on whether it meets the registry’s stated definition. The record does not describe an adjudication process or provide further rules for resolving uncertain causes.
The endpoint’s timeframe is up to day 100, while a secondary outcome measures NRM at day 365. Those are distinct follow-up horizons and should not be treated as interchangeable. The observed count for the primary endpoint is not reported in the registry record, so its frequency and precision cannot be assessed from the posted primary outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a small, single-group phase II study with enrollment of 6 and a terminated status. It identifies a treatment sequence and a primary endpoint, but it does not report the observed count for non-relapse mortality by day 100. As a result, the primary outcome’s observed magnitude cannot be described from the registry record. The study design alone does not indicate whether any participant experienced the endpoint.
The posted safety information reports 4 participants with serious adverse events among 6 at risk, 5 participants with other adverse events among 6 at risk, and 3 deaths. These are safety summaries, not the primary NRM result. The record does not state that all deaths met the NRM definition, and the endpoint specifically excludes deaths attributed to underlying disease progression or relapse. The death count therefore must not be substituted for the NRM count. The relationship between the safety counts, individual events, and endpoint classifications is not reported in the registry record.
In general, a count from a small group can be difficult to estimate precisely: each participant’s outcome has substantial influence on the observed group summary. A confidence interval, when reported, describes uncertainty around an estimate under a specified method; it does not remove uncertainty or correct for design limitations. No confidence interval for the primary outcome is reported in the registry record. Without the endpoint count and its analysis details, the primary outcome’s precision cannot be evaluated.
The single-group design also limits causal interpretation. There is no concurrent control group, and the record marks allocation as NA. Outcomes among participants who received the regimen do not show how the same participants would have fared under another treatment strategy. Differences from outcomes in other studies would not automatically be attributable to treatment, because populations, follow-up, outcome definitions, and care settings might differ; those comparison details are not reported.
The registry lists secondary outcomes covering mortality, graft-versus-host disease, survival, clinical response, and minimal residual disease response. However, the record reports 0 analyses, and the outcome information does not supply results for those measures in the registry record for this analysis. Their presence as registered outcomes should not be mistaken for evidence that results were observed or that they favored a particular conclusion. The reason for termination and the completeness of follow-up are not reported in the registry record.
Sample-size illustrations based on an observed effect, when presented, are planning exercises rather than observed power. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. The registry study itself is single-group, so those assumptions describe a hypothetical planning framework, not this trial’s allocation. Such illustrations do not supply a missing control group or establish that a future study would reproduce the observed effect.
9. Statistical Methods Explained
The primary outcome is a count of participants with an event, rather than a continuous measurement. This distinction matters because the statistical summaries and assumptions used for counts are not the same as those used for measurements such as laboratory values. The registry record identifies the primary measure as a participant count and defines the relevant event as non-relapse mortality up to day 100. It does not report an estimate, confidence interval, or analysis for that endpoint.
What does a participant count convey?
In general, a count tells how many participants in a defined group meet an outcome definition during a specified period. To interpret a count, readers also need the population at risk, the follow-up period, and a clear event definition. Here, the primary endpoint definition and timeframe are stated, but its observed count is not reported. The enrollment figure does not establish how many participants had evaluable endpoint data at day 100; that information is not reported in the registry record.
A count alone does not describe the uncertainty around an underlying event frequency. In general, estimates from a small group are especially sensitive to the outcome of each participant. A confidence interval can express sampling uncertainty around an estimate under its chosen method, but it cannot resolve uncertainty about missing follow-up, event classification, or selection into the study. No confidence interval or method for calculating one is reported for the primary endpoint.
Why does the event definition matter?
The NRM definition includes death due to graft-versus-host disease, infections, sepsis, or organ toxicity affecting the lung, liver, or kidney. It excludes death from underlying disease progression or relapse. A death is therefore not automatically an NRM event simply because it occurred during follow-up. In general, cause-specific endpoints rely on classification of the event’s cause, and unclear or competing causes can complicate that classification. The registry record does not describe adjudication, attribution procedures, or how uncertain causes would be handled.
The record also lists NRM at day 365 as a secondary outcome. In general, outcomes measured over different follow-up periods answer different questions: a longer period allows more time for events to occur and may also involve more incomplete follow-up. The day 100 and day 365 measures should therefore be interpreted according to their own timeframes, not treated as duplicate estimates. The registry record does not give follow-up completeness or specify how censoring would be handled.
What can a single-group design estimate?
A single-group study can report outcomes observed among participants receiving the regimen. It cannot directly estimate a treatment contrast against a concurrent group assigned to another strategy. In general, a randomized comparison helps balance prognostic factors across groups in expectation, while a single-group design has no such internal contrast. This record reports a single-group model, allocation marked NA, and masking marked none. It does not describe randomization or a blinded outcome assessment.
Without a control group, a descriptive count is not an estimate of the difference caused by treatment. Comparisons with other studies can be informative only with substantial care, because differences in eligibility, disease mix, clinical care, follow-up, and endpoint definitions can affect outcomes. The registry record does not provide external comparator data or a prespecified method for such comparisons.
How should sample-size illustrations be read?
In general, a sample-size calculation asks what study size might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. The registry’s stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a fraction of the observed effect. The assumptions describe planning illustrations, not the design of this single-group trial. They should not be read as evidence that the trial had a particular probability of detecting an effect, or as observed power.
The stated convention is that time-to-event illustrations give the total number of events, while other illustrations give participants per arm. In general, planning outputs depend on their assumptions, including the effect selected for detection and the analysis model. If those assumptions do not match a future study, the resulting planning figure may not apply. The registry record does not report that these assumptions formed the trial’s own design or statistical plan.
An observed effect used in a planning illustration is not necessarily a stable estimate of the effect expected in another study. In general, estimates based on a small study can be imprecise, and planning around an observed estimate may understate uncertainty about the true effect. The illustrations are not a substitute for an independently justified target effect or a documented protocol rationale. The sample-size justification for this trial is not reported in the registry record.
What is not specified about analysis?
The record lists 0 analyses. It does not report a statistical analysis plan, a model for the primary endpoint, an approach to missing outcome data, or an analysis population. It also does not describe interim analyses, subgroup analyses, or how secondary outcomes would be summarized. These details can affect interpretation, especially when a study has multiple outcomes or incomplete follow-up; their absence from the registry record means they cannot be assumed.
In general, multiplicity arises when several outcomes or statistical tests are considered. If many tests are performed, the chance of at least one apparently unusual result can increase unless the analysis strategy addresses that issue. This general concern does not establish that a particular adjustment was needed or used in this study. The registry record lists a primary outcome and secondary outcomes but does not report a multiplicity strategy. Results for unreported analyses should not be inferred from the list of outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies non-relapse mortality at day 100 as the primary outcome and lists secondary outcomes for NRM at day 365, acute and chronic graft-versus-host disease, overall and disease-free survival at one year, clinical responses, and minimal residual disease response. It reports 8 outcome measures and 0 analyses. The statistical plan, including any prespecified hierarchy among outcomes or adjustment for multiple testing, is not reported in the registry record.
In general, multiplicity is a concern when several outcomes or tests are examined, because interpreting each result separately can make apparently notable findings more likely by chance. A prespecified primary endpoint can help identify the central question, but the record does not state how secondary outcomes were to be interpreted relative to it. No multiplicity adjustment or testing procedure is reported, so none should be presumed.
Missing-data handling is also not reported. The record does not describe endpoint follow-up completeness, exclusions from an analysis, imputation, or how participants without complete outcome information would be handled. Enrollment of 6 does not itself establish that all enrolled participants contributed complete data to every outcome.
The analysis population is not reported in the registry record. It is therefore unclear whether analyses were intended to include all enrolled participants, only those who received the full regimen, or another defined group. The record also does not describe interim analyses or the statistical plan. These omissions prevent assessment of whether the posted outcome information, where available, follows a prespecified analysis strategy.
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 |
|---|---|---|---|
| All Participants - Treatment | 4 | 6 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Participants - Treatment | 3 of 6 |
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 |
|---|---|
| All Participants - Treatment | 5 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | All Participants - Treatment |
|---|---|---|
| Lung infection | Infections and infestations | 2 of 6 |
| Acute kidney injury | Renal and urinary disorders | 1 of 6 |
| Blood and lymphatic system disorders - Other | Blood and lymphatic system disorders | 1 of 6 |
| Death NOS | General disorders | 1 of 6 |
| Diarrhea | Gastrointestinal disorders | 1 of 6 |
| Hepatobiliary disorders - Other | Hepatobiliary disorders | 1 of 6 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
| Sepsis | Infections and infestations | 1 of 6 |
| Sinus disorder | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Participants - Treatment |
|---|---|---|
| Hypokalemia | Metabolism and nutrition disorders | 2 of 6 |
| Anemia | Blood and lymphatic system disorders | 1 of 6 |
| Blood bilirubin increased | Investigations | 1 of 6 |
| Creatinine increased | Investigations | 1 of 6 |
| Hypophosphatemia | Metabolism and nutrition disorders | 1 of 6 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
| Insomnia | Psychiatric disorders | 1 of 6 |
| Hypomagnesemia | Metabolism and nutrition disorders | 1 of 6 |
| Syncope | Nervous system disorders | 1 of 6 |
| Urinary tract infection | Infections and infestations | 1 of 6 |
Serious events with the highest arm-level rate: lung infection (33.3%), acute kidney injury (16.7%), blood and lymphatic system disorders - other (16.7%), death nos (16.7%), diarrhea (16.7%).
The registry record reports 4 participants with serious adverse events among 6 at risk and 5 participants with other adverse events among 6 at risk. It also reports 3 deaths. These are distinct safety summaries; the record does not explain the overlap among event categories or identify whether the deaths were classified as NRM. A death should not be treated as an NRM event without meeting the stated cause-specific definition.
The listed serious adverse event terms and percentages are lung infection, 33.3%; acute kidney injury, 16.7%; blood and lymphatic system disorders - other, 16.7%; death NOS, 16.7%; diarrhea, 16.7%; and hepatobiliary disorders - other, 16.7%. These percentages are reported as written. The registry record does not provide enough detail to determine from these terms whether events were related to treatment, how long participants were followed for safety, or whether a participant could contribute more than one event term.
In general, serious adverse event summaries describe reported events under the registry’s safety reporting conventions; they do not by themselves establish causation. With a small group and no comparator, these counts describe safety observations in the treatment group but cannot quantify an excess risk attributable to the regimen. The registry record does not report a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study evaluated a sequence of busulfan, fludarabine, donor stem cell transplantation, and cyclophosphamide in participants with multiple myeloma or myelofibrosis. It identifies non-relapse mortality by day 100 as the primary endpoint and gives a cause-based definition. It also records safety counts and lists secondary outcomes. Those details describe the registered study and its posted safety information.
The record does not report the observed primary endpoint count or analyses of the listed outcomes. Therefore, the primary outcome’s observed frequency, uncertainty, and relationship to other outcomes cannot be assessed from this information. The listed safety events and deaths should not be substituted for that missing endpoint result. In particular, the NRM definition excludes deaths attributed to underlying disease progression or relapse, and the record does not classify the reported deaths by cause.
The single-group design means that outcomes among treated participants do not provide an internal estimate of what would have happened under a different treatment. In general, an uncontrolled observation can describe what occurred in the study group, but it cannot isolate the effect of treatment from other influences. The registry record does not provide a concurrent control group or a randomized contrast.
The terminated status is reported, but the reason for termination is not. The record also does not report whether the intended enrollment was completed, the completeness of follow-up, or the analysis population. These omissions limit interpretation of both the registered objectives and any available safety summaries. The status alone should not be used to infer why the study ended or what its results were.
The sample-size assumptions describe planning illustrations rather than observed power or the trial’s own design. In general, planning calculations depend on assumptions about the target effect, analysis, and allocation. The stated equal-allocation, two-arm framework does not match the registered single-group model. It cannot be used to convert the study into a comparative trial or to infer an unreported treatment effect.
13. Why This Trial Matters Statistically
This study is statistically notable for the contrast between its clinical question and its design. The registered treatment involves a complex sequence of chemotherapy and donor stem cell transplantation, while the model is single-group and allocation is marked NA. The outcomes can be described for the treatment group, but the record does not include a randomized control group for estimating comparative effects. Recognizing that distinction is central to interpreting any reported count.
The primary endpoint also illustrates why event definitions matter. NRM is not defined as every death during follow-up: it includes specified treatment-related causes and excludes death from progression or relapse of the underlying disease. A death count and an NRM count are therefore not interchangeable. Cause attribution is part of the endpoint itself, and the registry record does not report the classification details or the observed primary count.
Small-group studies can be useful for describing feasibility and collecting clinical observations, but their estimates can be imprecise. In general, limited information makes each observed outcome influential and restricts what can be learned about uncommon events or variation across patient groups. The registry record reports enrollment of 6, but does not give disease-specific enrollment or complete outcome data. The safety summaries should consequently be read as descriptions, not as stable comparative risk estimates.
The record further highlights the importance of separating study design from sample-size planning illustrations. The stated planning assumptions use equal allocation between two arms, whereas the registered study is single-group. These illustrations are not evidence of observed power, nor do they establish the planned statistical basis for this trial. The statistical plan and sample-size justification are not reported in the registry record.
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 study is registered as single-group, with allocation marked NA and masking marked none. It has no concurrent comparator in the record, so treatment outcomes cannot be contrasted within the study against outcomes under another strategy. The registry record does not report an external comparison or a method for adjusting one.
Enrollment is reported as 6, and the status is terminated. The reason for termination and whether intended enrollment was reached are not reported in the registry record. The record does not provide the number of participants with multiple myeloma versus myelofibrosis, nor does it describe disease-specific eligibility or outcome summaries. This limits the ability to understand the clinical composition of the group.
The primary endpoint is defined, but its observed count is not reported in the information available for this analysis. The registry record also lists 0 analyses, without reporting confidence intervals, analysis methods, or an analysis population. Follow-up completeness, missing-data handling, and endpoint adjudication procedures are not reported. These gaps prevent assessment of the precision and completeness of outcome estimates.
Safety summaries include serious events, other adverse events, and deaths, but the record does not describe event overlap, attribution to treatment, or the relation between deaths and NRM classification. The reason for termination and any interim analyses are not reported. The multiplicity strategy for the listed primary and secondary outcomes is also not reported.
Finally, the planning assumptions describe hypothetical two-arm, equal-allocation calculations, while the study design is single-group. The illustrations should not be mistaken for the trial’s own design rationale or observed power. The sample-size justification and statistical plan are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis — NCT03303950.
- Registry record last updated 2022-05-05; status last verified 2022-05.
- Results first posted 2020-05-27.
- 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
NCT03303950 is a phase II, single-group study sponsored by the University of Utah. It evaluates busulfan and fludarabine before donor stem cell transplantation, followed by cyclophosphamide, for participants with multiple myeloma or myelofibrosis. The registry reports enrollment of 6, status terminated, a start date of 2018-03-30, and a primary completion date of 2019-05-14.
The primary outcome is the count of participants with non-relapse mortality up to day 100, with deaths from specified complications included and deaths from underlying disease progression or relapse excluded. The observed primary outcome count is not reported in the registry record. Safety summaries report serious and other adverse events and deaths, but the record does not establish their relation to the primary endpoint. The reason for termination, analysis plan, missing-data approach, and analysis population are not reported.