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 HM2014-26 DT2219 for Relapsed or Refractory B-Lineage Leukemia or Lymphoma (NCT02370160), a na phase 1, phase 2 study. The primary outcome is Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02370160 |
| Phase | Phase 1, Phase 2 |
| Condition | Refractory B-Lineage Leukemia, Relapsed B-Lineage Leukemia, Refractory B-Lineage Lymphoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Masonic Cancer Center, University of Minnesota |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with relapsed or refractory B-lineage leukemia or lymphoma. The official title specifies CD19 (+) and/or CD 22 (+) disease. The listed conditions include relapsed and refractory B-lineage leukemia and relapsed and refractory B-lineage lymphoma. The registry record does not give further eligibility details in the information available for this analysis.
Intervention
Participants received DT2219ARL, described as a recombinant bispecific antibody-targeted toxin. The record describes a phase I dose and schedule finding component and a phase II extension using the dose identified in phase I. It does not report treatment outcomes for the primary endpoint.
Comparator
There was no concurrent control group: the design is listed as single group, allocation is NA, and masking is none. The dose groups are parts of the study rather than randomized comparison arms. Their results should not be read as a like-for-like comparison of treatment strategies.
Primary question
The primary endpoint asks how many participants experienced a dose-limiting toxicity attributed to DT2219 during the first treatment cycle. The registry defines the qualifying adverse events and gives the timeframe as Day 1 - Day 29. The endpoint is intended to inform dose and schedule decisions in phase I; it is not itself a direct measure of antitumor activity.
The study also planned a phase II extension to confirm safety and make a preliminary determination of activity by disease. The registry lists secondary outcomes including duration of response, disease-free survival, overall survival, and time to relapse or progression. Results for those outcomes are not reported in the registry record. Consequently, the central statistical question that can be read from this record is about the planned safety endpoint and study structure, rather than an estimate of activity or a comparative treatment effect.
3. Trial Design
This is a phase I/II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. The record lists a total enrollment of 18 and a status of completed. The study started on 2015-12-21, and its primary completion date is 2018-04-08. These dates describe the registry record and do not provide information about the timing or completeness of individual participants’ follow-up.
The brief summary describes two components. In phase I, the study sought to find a dose and schedule, using the maximum tolerated dose identified during the previous phase I study but with a higher number of doses. A phase II extension was described as having two stages, with the aim of confirming safety and making a preliminary determination of activity by disease using the dose identified in phase I. The record does not report the detailed protocol rules for dose escalation, dose selection, or the two-stage extension.
Three groups are listed in the adverse-event information: DT2219ARL 60 µg/kg/Dose (Phase I), DT2219 80 µg/kg/Dose (Phase I), and DT2219 (Phase II). The record lists 9, 6, and 3 participants at risk for serious adverse events in these groups, respectively. Because the study is not randomized and has no concurrent control group, the groups should not be treated as randomized arms. Differences between them could reflect their phase, dose, participant composition, follow-up, or other factors not described in the registry record.
Masking is listed as none. That describes the study’s masking status but does not, by itself, explain how endpoint events were assessed. The record does not report further details about assessment procedures, analysis populations, or handling of participants who did not complete treatment or follow-up.
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 | DT2219ARL 60 µg/kg/Dose (Phase I) | DT2219 80 µg/kg/Dose (Phase I) | DT2219 60 µg/kg/Dose (Phase II) |
|---|---|---|---|
| STARTED | 9 | 6 | 3 |
| COMPLETED | 6 | 2 | 2 |
| NOT COMPLETED | 3 | 4 | 1 |
Reasons for not completing this period:
| Reason | DT2219ARL 60 µg/kg/Dose (Phase I) | DT2219 80 µg/kg/Dose (Phase I) | DT2219 60 µg/kg/Dose (Phase II) |
|---|---|---|---|
| Death | 3 | 4 | 1 |
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 | DT2219ARL |
|---|---|---|
| Participants analysed | 18 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 12 |
| Age, Continuous | years | 68.11 (SD 7.75) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 11 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| 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 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | Participants | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle, measured over Day 1 - Day 29.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts events of dose-limiting toxicity attributed to DT2219 during the first treatment cycle. The registry describes the endpoint as the incidence of any such DLT and gives its unit as events. Its definition covers specified serious or severe adverse events occurring from study day 1 through 7 days after the last dose of DT2219 of the first cycle, when not clearly attributed to the primary malignancy or an intercurrent illness. The listed events include any Grade 5 adverse event; prolonged Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 non-hematologic adverse events during infusion; and Grade 3 non-hematologic adverse events after infusion. The recorded timeframe is Day 1 - Day 29.
As a general statistical concept, a DLT endpoint is used in early-phase research to describe toxicity that may be important to dose and schedule decisions. Counting qualifying events makes the endpoint interpretable as a safety outcome within the specified observation window. The count does not, by itself, describe how frequently events occur relative to exposure time, how severe events outside the definition were, or whether events were caused by treatment with certainty.
The registry record does not report the primary endpoint result. It therefore does not establish how many participants met the DLT definition, nor does it permit an estimate of the uncertainty around that count from the information recorded.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry presents a study designed to examine DT2219 in relapsed or refractory B-lineage leukemia or lymphoma, with an early-phase focus on dose-limiting toxicity and a later phase II extension intended to assess safety and preliminary activity by disease. The available record identifies the primary endpoint and its definition, but does not report the observed primary endpoint result. No conclusion about the frequency of DLTs in the study can be drawn from the endpoint description alone.
The study is listed as single group, with allocation NA and masking none. This means that its design does not support a randomized comparison with an untreated or alternative-treatment control group. The listed dose and phase groups are not a like-for-like control comparison. Any apparent difference across those groups would require careful interpretation because group membership, dose, phase, disease mix, and follow-up may differ. The registry record does not provide enough detail to resolve those potential differences.
The enrollment is listed as 18, and the adverse-event record reports group-specific numbers at risk. Those figures describe the population represented in the safety summary, not necessarily the number included in every outcome analysis. The analysis populations and the treatment of missing outcome data are not reported in the registry record. Serious adverse events and other adverse events are recorded separately by group; the reported counts should be read as descriptive safety information rather than as a controlled estimate of excess risk or treatment effect.
In general, a count of events is most informative when its observation window, population, event definition, and denominator are clear. Here, the registry specifies a DLT definition and a timeframe, but does not give the endpoint count or an uncertainty interval. A count without its corresponding outcome result cannot indicate precision, and an enrollment total alone cannot substitute for an outcome denominator.
The brief summary states that the phase II extension was intended to confirm safety and make a preliminary determination of activity by disease. This is a statement of study purpose, not evidence that safety was confirmed or that activity was observed. The secondary outcomes listed include duration of response, disease-free survival, overall survival, and time to relapse or progression, but their results are not reported in the registry record. The available information therefore supports a description of the study question and design, not a numerical assessment of efficacy or a comparison with other treatment options.
In general, statistical interpretation should distinguish the planned question from the evidence actually reported. The registry gives substantial detail about the kinds of events that qualify for the primary endpoint and gives a small number of safety summaries, but it does not provide the primary result or the analysis details needed to quantify its uncertainty. Any claim beyond those descriptive details would go beyond what the registry record reports.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group study describes outcomes among participants who receive the study intervention. It can characterize observed events in the enrolled group, but without a concurrent control group it cannot directly estimate what would have happened to comparable participants under a different treatment or no study treatment. That limitation matters especially when interpreting safety events, because disease, intercurrent illness, and treatment can all be relevant to whether an event occurs.
This record identifies the study model as single group, allocation as NA, and masking as none. It also lists distinct phase and dose groups in the safety information. These group labels do not create randomized comparison arms. Comparing their observed counts as if treatment allocation had made the groups exchangeable would require assumptions that the record does not establish.
How should a count endpoint be read?
In general, a count endpoint records the number of qualifying events within a defined population and observation period. Its interpretation depends on a precise event definition and on knowing who was observed. The registry defines DLT using specified adverse-event grades, types, timing, and attribution conditions, and identifies the first cycle as the period of interest. This operational definition makes clear which events belong in the endpoint, but the registry record does not report the number that met it.
Counts can also be analyzed using models that make assumptions about event generation. A simple count model may assume that the expected count and variability are closely related. In general, over-dispersion means that observed variability is greater than such a model expects; ignoring it can make uncertainty estimates too narrow. Whether the primary endpoint was modeled as a count, as a participant-level indicator, or by another method is not reported in the registry record. No model choice should be inferred from the endpoint label alone.
What does a confidence interval convey?
In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the analysis method. A narrow interval indicates greater statistical precision than a wide interval, but neither width nor location by itself establishes clinical importance. For a safety outcome, the interval would need to accompany an endpoint estimate defined for a clear population and observation window. The registry record does not report an interval for the primary DLT endpoint, so its precision cannot be assessed from the recorded information.
A p-value, in general, summarizes how compatible the observed data are with a specified null model under the assumptions used. It does not measure the probability that a treatment is effective, and it does not measure the size or importance of an effect. The registry record does not report a primary endpoint p-value or a control-group comparison. A significance test is therefore not a basis for interpreting the primary endpoint in this record.
Why do denominators and follow-up matter?
In general, a proportion requires a defined numerator and denominator. For adverse events, the number of participants at risk and the number with an event describe a participant-level summary, while an event count may include repeated events in the same participant. These are different quantities. The registry identifies participants at risk and affected for the serious and other adverse-event summaries, but does not state whether every reported event count represents unique participants or repeated events. The DLT endpoint is described in events, and its result is not reported.
Time-to-event outcomes, such as survival or time to progression, also depend on follow-up and censoring. Censoring occurs when the event has not been observed by the last available follow-up; it does not mean that the event will never happen. In general, time-to-event methods account for this incomplete observation when their assumptions are appropriate. Although the registry lists overall survival, disease-free survival, and time to relapse or progression as secondary outcomes, methods and results for those outcomes are not reported in the registry record.
What can the phase structure tell the reader?
The record describes phase I dose and schedule finding and a two-stage phase II extension. In general, these components have different objectives: early dose-finding work is focused on tolerability and selection, while an extension may gather additional safety and preliminary activity information. The description does not specify the actual decision rules, stopping boundaries, or statistical model for either component. Such details are not reported in the registry record and should not be reconstructed from the phase labels.
The record says phase I used the maximum tolerated dose identified during the previous phase I study, with a higher number of doses, and that phase II would use the dose identified in phase I. This describes the intended approach, but it does not establish what dose was selected, whether every participant received the same schedule, or how any changes were handled. Those details are not reported in the registry record.
Overall, the statistical information supports explanation of the endpoint and the design, but it does not support an independent efficacy estimate or a reanalysis of the primary endpoint. In general, interpretation should be tied to reported estimates, denominators, uncertainty, and analysis rules. Where those are absent, the appropriate conclusion is that the registry record does not report them.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including the primary DLT endpoint and secondary outcomes for serious adverse events, duration of response, disease-free survival, overall survival, and time to relapse or progression. In general, examining multiple outcomes can increase the chance of finding an apparently notable result by chance, particularly when many statistical tests are performed. A prespecified strategy can address this issue by defining a primary outcome, controlling error rates, or treating secondary findings as exploratory. The registry record does not report a multiplicity adjustment or a detailed testing hierarchy.
The record describes a two-stage phase II extension intended to confirm safety and make a preliminary determination of activity by disease. It does not report stage-specific decision rules, interim analyses, stopping boundaries, or how multiple disease-specific assessments were handled. These elements are not reported in the registry record, so the phrase two-stage should not be taken to imply any particular statistical design.
Missing outcome data can affect both the estimated event frequency and its uncertainty. In general, results may depend on whether participants with incomplete follow-up are excluded, counted as having no event, or handled using another method. For time-to-event outcomes, censoring is relevant; for a cycle-limited safety endpoint, completeness of observation during the defined period matters. The registry record does not report how missing data, incomplete cycles, or loss to follow-up were handled.
Analysis populations also affect interpretation. In general, an analysis may include all enrolled participants, only those who received treatment, or a subset meeting specified evaluability rules. The record lists enrollment and group safety denominators but does not define the population used for the primary endpoint or for each secondary outcome. These omissions limit assessment of whether the planned and reported populations align.
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 |
|---|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | 2 | 9 | 22.2% |
| DT2219 80 µg/kg/Dose (Phase I) | 2 | 6 | 33.3% |
| DT2219 (Phase II) | 1 | 3 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | 3 of 9 |
| DT2219 80 µg/kg/Dose (Phase I) | 4 of 6 |
| DT2219 (Phase II) | 1 of 3 |
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 |
|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | 9 of 9 |
| DT2219 80 µg/kg/Dose (Phase I) | 6 of 6 |
| DT2219 (Phase II) | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | DT2219ARL 60 µg/kg/Dose (Phase I) | DT2219 80 µg/kg/Dose (Phase I) | DT2219 (Phase II) |
|---|---|---|---|---|
| Sepsis | Infections and infestations | 2 of 9 | 0 of 6 | 0 of 3 |
| Capillary leak syndrome | Vascular disorders | 0 of 9 | 1 of 6 | 0 of 3 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 9 | 1 of 6 | 0 of 3 |
| Lung infection | Infections and infestations | 0 of 9 | 0 of 6 | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DT2219ARL 60 µg/kg/Dose (Phase I) | DT2219 80 µg/kg/Dose (Phase I) | DT2219 (Phase II) |
|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 9 of 9 | 4 of 6 | 3 of 3 |
| Aspartate aminotransferase increased | Investigations | 8 of 9 | 5 of 6 | 3 of 3 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 7 of 9 | 4 of 6 | 3 of 3 |
| Anemia | Blood and lymphatic system disorders | 6 of 9 | 3 of 6 | 2 of 3 |
| Platelet count decreased | Investigations | 6 of 9 | 2 of 6 | 2 of 3 |
| Fatigue | General disorders | 5 of 9 | 2 of 6 | 2 of 3 |
| Hypocalcemia | Metabolism and nutrition disorders | 4 of 9 | 3 of 6 | 2 of 3 |
| Lymphocyte count decreased | Investigations | 5 of 9 | 1 of 6 | 1 of 3 |
| Hypokalemia | Metabolism and nutrition disorders | 3 of 9 | 2 of 6 | 0 of 3 |
| Neutrophil count decreased | Investigations | 2 of 9 | 1 of 6 | 2 of 3 |
Serious events with the highest arm-level rate: lung infection (33.3%), sepsis (22.2%), capillary leak syndrome (16.7%), febrile neutropenia (16.7%).
The safety record separates serious adverse events from other adverse events and lists participants at risk and affected within three groups. For DT2219ARL 60 µg/kg/Dose (Phase I), 9 participants were at risk for serious adverse events and 2 were affected; 9 were at risk for other adverse events and 9 were affected. For DT2219 80 µg/kg/Dose (Phase I), the corresponding counts are 6 at risk and 2 affected for serious adverse events, and 6 at risk and 6 affected for other adverse events. For DT2219 (Phase II), 3 were at risk and 1 was affected for serious adverse events, while 3 were at risk and 3 were affected for other adverse events.
The record also lists deaths of 3, 4, and 1 across those groups, respectively. These figures are presented as deaths in the adverse-event summary; the registry information does not establish that they were caused by DT2219. The listed serious-event terms include lung infection at 33.3%, sepsis at 22.2%, capillary leak syndrome at 16.7%, and febrile neutropenia at 16.7%. The denominator and method used for these percentages are not reported in the registry record.
These are descriptive summaries from small, nonrandomized groups, not comparative estimates. Serious adverse-event counts should not be conflated with the primary DLT endpoint, which has its own definition and timeframe and whose result is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase I/II study of DT2219 was conducted in people with relapsed or refractory B-lineage leukemia or lymphoma, and describes a primary safety question focused on dose-limiting toxicity during the first treatment cycle. It also states that a phase II extension was intended to confirm safety and make a preliminary determination of activity by disease. These are features of the study’s purpose and design, rather than findings about treatment effects.
The record does not report the primary DLT result. It therefore does not show how many participants met the endpoint definition, what proportion of an analysis population experienced a DLT, or how precisely any such estimate was measured. The listed serious and other adverse-event summaries provide descriptive safety counts, but they are not equivalent to the DLT outcome and do not establish causation.
Because this is a single-group study without a concurrent control, the registry information does not support a randomized comparison or a causal estimate of benefit or harm relative to another treatment. The phase and dose groups are not like-for-like control groups. Differences in their summaries cannot be attributed to dose or phase alone from the information reported.
The registry lists response duration, disease-free survival, overall survival, and time to relapse or progression among the secondary outcomes. Their results are not reported in the registry record. The described intent to assess activity does not substitute for outcome estimates, and the available record cannot establish whether activity was observed or how uncertain such an assessment would be.
In general, a trial’s design can explain what it was intended to investigate, while its results are needed to estimate what was observed. Here, the design and endpoint definitions are described, and some adverse-event summaries are recorded, but the main endpoint result and analysis details are absent. The appropriate interpretation is limited to those reported features; conclusions about efficacy or comparative safety would exceed the registry information.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between a clearly described endpoint and a reported endpoint result. The registry gives a detailed operational definition of dose-limiting toxicity, including event type, grade, attribution, and timing. Those details are essential because a safety endpoint is only interpretable when readers know which events count. However, the definition alone cannot answer how often the endpoint occurred. Without its observed result and an analysis population, the central safety estimate cannot be assessed.
The phase I/II structure also shows why design context matters. Dose and schedule finding and an extension for safety and preliminary activity have related but distinct aims. The record describes the broad intentions, while leaving the specific dose-selection and stage decision procedures unreported. Statistical interpretation must therefore avoid assigning unreported rules or treating phase groups as if they were randomized.
The adverse-event summaries demonstrate another general lesson: counts need context. Readers need to distinguish participants affected from event totals, identify the population at risk, understand the observation period, and know whether events were assessed consistently. A group-specific count is descriptive, but in a single-group study it does not provide a controlled estimate of comparative risk.
Finally, the listed secondary outcomes imply a broad set of safety and disease-course questions, but their results are not reported in the registry record. This makes it important to distinguish planned assessment from available evidence and to be cautious about multiplicity and missing analysis details. The record is useful for understanding the study’s clinical question and endpoint framework, while also showing the limits of statistical conclusions when outcome estimates and methods are not reported.
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 that the registry record does not report the primary endpoint result. Although it defines DLT and specifies its observation timeframe, the event count and corresponding analysis denominator are absent. The record therefore does not permit assessment of the observed DLT frequency or its precision.
The study is single group, with allocation NA and masking none. There is no concurrent randomized control group against which to interpret safety or activity. The phase and dose groups in the adverse-event summary are not like-for-like controls, and the information recorded does not establish that they are comparable in disease characteristics, follow-up, or other relevant features.
The registry provides limited information about analysis procedures. It does not report the statistical plan, analysis populations, missing-data handling, interim analyses, phase-specific decision rules, or multiplicity strategy. It also does not report the denominator and calculation basis for the percentages attached to the serious-event terms. These gaps restrict interpretation of both the endpoint and the safety summaries.
The enrollment of 18 and the listed group counts describe a small study, but the registry record does not provide enough detail to determine the number evaluable for each endpoint or the completeness of follow-up. The listed deaths do not include a reported attribution basis in the information. Nor are results reported for the listed response and survival outcomes. These limitations mean that the record supports description of study design and selected safety summaries, not a broad conclusion about efficacy or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: HM2014-26 DT2219 for Relapsed or Refractory B-Lineage Leukemia or Lymphoma — NCT02370160.
- Registry record last updated 2020-01-13; status last verified 2019-12.
- Results first posted 2020-01-13.
- 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
NCT02370160 is a completed phase I/II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. It enrolled 18 participants with relapsed or refractory B-lineage leukemia or lymphoma and evaluated DT2219, described as a recombinant bispecific antibody-targeted toxin. The record describes phase I dose and schedule finding followed by a two-stage phase II extension intended to confirm safety and make a preliminary determination of activity by disease.
The primary endpoint is the incidence of any DLT attributed to DT2219 during the first cycle, with a recorded timeframe of Day 1 - Day 29. The registry defines qualifying events but does not report the primary endpoint result. It provides descriptive serious and other adverse-event counts for three phase or dose groups, as well as selected serious-event terms and death counts. The study has no concurrent control group, and analysis methods, missing-data procedures, and results for the listed secondary outcomes are not reported in the registry record.