Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine & Mitoxantrone for Untreated AML & High-Grade Myeloid Neoplasm: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine & Mitoxantrone for Untreated AML & High-Grade Myeloid Neoplasm (NCT03531918), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1).

2. Clinical Question

3. Trial Design

This was a single-center phase 1/2 study of gemtuzumab ozogamicin combined with G-CSF, cladribine, cytarabine, and mitoxantrone for previously untreated adults with acute myeloid leukemia or high-grade myeloid neoplasm. The registry lists the study as completed and gives an enrollment of 66. The start date is 2018-09-14 and the primary completion date is 2021-07-01. These dates describe the study record; they do not establish when particular outcomes were assessed or reported.

The treatment description includes a single-dose GO schedule on day 1 and a fractionated schedule on days 1, 4, and 7. G-CSF was given subcutaneously on days 0-5, while cladribine and cytarabine were given intravenously over 2 hours on days 1-5. Mitoxantrone is listed as part of the regimen, but its administration description is truncated in the registry record. The protocol’s detailed dose-escalation process and the dose levels studied are not reported in the registry record.

The design is listed as single-group, with allocation marked NA and masking listed as none. Consequently, this record does not describe a randomized comparison with a separate control treatment. It lists GO1 Dose Level Phase 1 and GO3 Dose Level Includes Phase 1 and Phase 2 in the adverse-event summary. Those group labels should not be read as evidence of randomized, comparable arms.

The primary endpoint is the phase 1 MTD of GO when added to GCLAM. Secondary outcomes include 30-day all-cause mortality, relapse-free survival for the GO3 cohort, overall survival, and remission and measurable residual disease outcomes. The registry lists 10 outcome measures, but reports no analyses in its analysis count. Outcome values, analysis populations, and detailed methods for those secondary endpoints are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1), measured over At time of count recovery, second cycle of treatment, response assessment or removal from protocol (at approximately 1 month)..

The primary endpoint asks for the maximum tolerated dose of gemtuzumab ozogamicin when added to GCLAM in the phase 1 portion. The registry defines MTD as the highest dose studied at which the incidence of dose-limiting toxicity is ≤33% (≤4 of 12 patients experiencing DLT). A DLT includes specified severe or prolonged non-hematologic toxicities, subject to listed exceptions, and is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

This endpoint is used in early-phase dose-finding because a combination’s dose needs to be assessed alongside its toxicity profile. The MTD definition expresses a decision threshold for dose-limiting toxicity; it is not itself a measure of antileukemic benefit. The registry’s assessment timeframe runs to count recovery, a second treatment cycle, response assessment, or removal from protocol, at approximately 1 month.

The endpoint description explains what was intended to be measured, but the registry record does not report the selected MTD, the observed dose-limiting toxicity counts by dose, or the number of participants assessed for this endpoint. Therefore, the endpoint definition can be described, but its observed result cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a phase 1/2, single-group study with allocation marked NA and masking listed as none. This design is consistent with evaluating a dose and describing outcomes in participants receiving a treatment combination, rather than estimating a randomized contrast against a control. The record does not report a detailed statistical analysis plan, a sample-size justification, or a prespecified interim-analysis plan.

What does the MTD endpoint capture?

The primary endpoint is a dose-selection measure based on dose-limiting toxicity. Under the registry definition, MTD is the highest studied GO dose at which the DLT incidence is ≤33% (≤4 of 12 patients experiencing DLT). A DLT includes specified grade and duration criteria for non-hematologic toxicity, with exceptions for febrile neutropenia, infection, and certain related toxicities or recovery patterns. The criteria refer to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

In general, dose-finding endpoints summarize tolerability within the rules defined by a study. They do not, by themselves, show that a regimen is effective or that the selected dose is optimal for every later study. The threshold is part of the endpoint definition, not an observed result. Because the registry does not report dose-specific DLT counts or an MTD conclusion, the endpoint cannot be reconstructed from the recorded information.

How should the group counts be understood?

The adverse-event summary reports participants at risk and participants affected for serious and other events, alongside deaths, for two labeled dose-level groups. These are counts, not adjusted comparisons. The registry lists GO1 Dose Level Phase 1 and GO3 Dose Level Includes Phase 1 and Phase 2; it does not describe randomized allocation between them. The counts should therefore be read as descriptive group summaries and not as estimates of the effect of GO versus a control treatment.

In general, event counts depend on who was observed, how long they were followed, how events were defined, and how completely events were recorded. The registry record does not provide detailed follow-up durations or the analysis population for these summaries. The percentages listed beside selected serious-event terms are reported as such; they should not be combined into a total, because the record does not establish that the terms are mutually exclusive.

What does a planning illustration tell the reader?

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event outcomes, the described planning quantity is the total number of events; for other outcomes, it is participants per arm for 80% or 90% power.

These are planning illustrations, not observed power and not evidence that the single-group trial had a randomized two-arm design. The assumptions are not a substitute for a trial-specific design justification. The record does not report the calculations’ inputs or a sample-size justification, and the design listed for this study is not randomized between two arms. Accordingly, any such illustration should be understood as a hypothetical planning exercise, not as an analysis of the trial’s actual design or outcomes.

What uncertainty can be assessed?

In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval, and a clear definition of the analysis population. A confidence interval communicates precision under the chosen statistical model and assumptions; it does not address every source of bias. The registry record does not report a primary endpoint estimate, confidence interval, or analysis population. It also lists no analyses in its analysis count. The available information supports description of endpoint definitions, design features, and adverse-event counts, but not an independent inferential analysis of treatment efficacy.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including 30-day all-cause mortality, relapse-free survival for the GO3 cohort, overall survival, and remission and measurable residual disease outcomes. The presence of multiple outcomes raises a general statistical consideration: when many hypotheses are tested, the chance of a seemingly notable result arising by chance can increase. Whether and how that issue was addressed depends on a prespecified analysis plan. Multiplicity procedures or a hierarchy of outcomes are not reported in the registry record, so no claim can be made about adjustment or prioritization.

Missing-data methods and rules for handling participants who did not complete assessments are also not reported in the registry record. The record does not specify the analysis populations for the primary or secondary outcomes, how incomplete follow-up was handled, or whether all participants were included in each analysis. These details matter because an outcome may be available for some participants but not others, and the consequences depend on why data are missing and on the analysis approach.

The registry lists 10 outcome measures but reports no analyses in its analysis count. It does not provide endpoint results, inferential tests, or confidence intervals for the outcomes listed. Therefore, the registered outcome names alone cannot establish whether multiplicity was controlled or whether missing data affected a result. Such information would be needed for a fuller assessment of the statistical interpretation.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: grade 3 left ventricular systolic dysfunction (16.7%), grade 3 intercranial hemorrhage (3.3%), grade 4 respiratory failure (3.3%), grade 4 bronchopulmonary hemorrhage (1.7%), grade 4 aspartate aminotransferase increase (1.7%).

The safety summary separates two dose-level groups and reports participants at risk, participants affected by serious adverse events, participants affected by other adverse events, and deaths. In GO1 Dose Level Phase 1, serious events are reported for 1 of 6 participants and other events for 6 of 6; the death count is 0. In GO3 Dose Level Includes Phase 1 and Phase 2, serious events are reported for 10 of 60 and other events for 59 of 60; the death count is 2.

The registry’s selected serious-event terms include Grade 3 Left Ventricular Systolic Dysfunction at 16.7%, Grade 3 Intercranial Hemorrhage at 3.3%, Grade 4 Respiratory Failure at 3.3%, Grade 4 Bronchopulmonary Hemorrhage at 1.7%, Grade 4 Aspartate Aminotransferase Increase at 1.7%, and Grade 3 Reversible Posterior Leukoencephalopathy Syndrome at 1.7%. These are event-term summaries, not estimates of comparative risk.

In general, adverse-event summaries describe events recorded during a study; they do not by themselves prove causation. The registry does not report event timing, duration, attribution, or the follow-up period for these group summaries. The death counts are reported without cause or timing in the safety summary, so they should not be interpreted as treatment-related deaths. The groups are not randomized control arms, and their counts should not be contrasted as if they came from a like-for-like comparison.

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

The registry record establishes the study question and design: a single-center phase 1/2 evaluation of GO with GCLAM for previously untreated adult acute myeloid leukemia or high-grade myeloid neoplasm, with the phase 1 primary endpoint focused on MTD. It also records selected adverse-event counts and lists several secondary outcomes. These details are useful for understanding what the study set out to evaluate and what safety summaries were recorded.

The record does not report the primary endpoint result, dose-specific DLT findings, or numerical results for remission, measurable residual disease, relapse-free survival, overall survival, or 30-day all-cause mortality. It therefore does not establish the observed MTD or provide an efficacy estimate. A trial’s completed status and a list of intended outcomes do not substitute for results.

The safety counts describe events in the recorded groups, but do not support a causal conclusion. There is no randomized control group, and the GO1 and GO3 labels represent different dose-level groups with different phase coverage. The record does not establish that their participant groups, follow-up, or event ascertainment are comparable. Nor does the event summary identify which events investigators judged related to treatment.

In general, statistical evidence depends on both the observed estimate and its uncertainty, along with the design and analysis assumptions. The registry record does not provide a primary endpoint estimate with a confidence interval or details sufficient to evaluate the secondary outcome analyses. This means that no conclusion about comparative treatment benefit, the precision of an efficacy effect, or the generalizability of outcomes follows from these registry entries alone.

The appropriate reading is narrow: the record describes a dose-finding and treatment-combination study, its endpoint definition, and selected safety counts. It does not answer whether the combination improves outcomes relative to another treatment, and it does not report enough primary endpoint information to determine which GO dose met the stated MTD rule.

13. Why This Trial Matters Statistically

This study is statistically notable for combining an early-phase dose-finding question with a phase 2 evaluation in a single-center, single-group design. Its primary endpoint is not a conventional randomized treatment contrast; it is a dose-selection rule based on dose-limiting toxicity. Distinguishing those questions matters because a threshold-based MTD endpoint and a comparative efficacy estimate answer different questions.

The record also illustrates why endpoint definitions and endpoint results must be distinguished. It gives a detailed DLT definition and threshold, including toxicity grades, duration requirements, exceptions, and a timeframe of approximately 1 month. But without observed DLT counts by dose and a reported MTD conclusion, the definition cannot be converted into a result. Clear endpoint detail is valuable, while missing result detail limits statistical interpretation.

The study’s design also affects what can be concluded from its safety counts. A single-group study can describe events within treated participants, but without a separate randomized control group it cannot isolate the treatment’s contribution to those events. GO1 and GO3 are labeled as dose-level groups, and one includes both phase 1 and phase 2; they are not described as randomized comparators. Recognizing that distinction prevents descriptive counts from being treated as causal contrasts.

Finally, the registry lists a broad set of secondary outcomes but no analyses in its analysis count. For researchers, that gap highlights the importance of complete outcome reporting, analysis-population definitions, uncertainty estimates, and a transparent approach to multiplicity and missing data. These elements allow readers to assess not only what was measured, but how firmly the data support the interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation of the registry record for statistical interpretation is that it does not report the primary endpoint result. The MTD definition is detailed, but dose-specific DLT counts, the selected dose, and uncertainty around that decision are not reported in the registry record. The record also does not report numerical results for the listed remission, measurable residual disease, survival, and mortality outcomes.

The single-group design has no randomized control arm, so the posted safety counts cannot provide a like-for-like treatment comparison. The GO1 and GO3 groups have different labels and phase coverage, and the registry does not report enough information to determine whether their participants or observation periods are comparable. The record does not give detailed follow-up durations, event attribution, or missing-data methods for the adverse-event summaries.

Further limitations include the absence of a reported statistical analysis plan, sample-size justification, analysis populations, and methods for multiplicity. The registry lists 10 outcome measures but reports no analyses in its analysis count. It does not report confidence intervals for the primary endpoint or the listed secondary outcomes, limiting assessment of precision.

The treatment description is also incomplete for mitoxantrone administration. More generally, the registry record alone does not provide full eligibility criteria, dose-escalation procedures, or enough operational detail to evaluate all aspects of conduct and analysis. These limitations constrain interpretation of the recorded design and safety counts; they do not establish that unreported analyses or procedures were not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine & Mitoxantrone for Untreated AML & High-Grade Myeloid Neoplasm — NCT03531918.
• Registry record last updated 2023-08-30; status last verified 2023-08.
• Results first posted 2022-11-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03531918 is a completed, single-center phase 1/2 study of gemtuzumab ozogamicin with G-CSF, cladribine, cytarabine, and mitoxantrone for previously untreated adult acute myeloid leukemia or high-grade myeloid neoplasm. The registry records an enrollment of 66, a start date of 2018-09-14, and a primary completion date of 2021-07-01.

The primary endpoint is the phase 1 maximum tolerated dose of GO added to GCLAM, defined using a dose-limiting toxicity threshold of ≤33% (≤4 of 12 patients experiencing DLT). The registry record does not report the MTD result. It includes adverse-event counts for GO1 and GO3 dose-level groups and lists secondary survival, remission, and measurable residual disease outcomes, but does not report their analysis results.

The single-group design does not provide a randomized control comparison. The recorded safety counts are descriptive and do not establish causation or comparative effects. Statistical analysis details, including missing-data methods, analysis populations, and multiplicity procedures, are not reported in the registry record.