Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia (NCT01743807), a non-randomized phase 1 study. The primary outcome is Number of Patients With Dose Limiting Toxicity (DLT) in the First Two Courses of Therapy.

2. Clinical Question

3. Trial Design

This was a phase I, non-randomized, single-group study of GNKG168 in pediatric patients with ALL or AML. The registry lists relapsed ALL and relapsed acute myelogenous leukemia as conditions. Its brief summary describes relapsed and refractory disease in patients who were in morphologic remission but remained positive for MRD. Four participants were enrolled. The study status is terminated; the reason for termination is not reported in the registry record.

The registry describes two participant categories based on prior HSCT: participants with a history of HSCT and participants who had never undergone HSCT. Both descriptions specify GNKG168 as a 60-minute intravenous infusion daily for five consecutive days. Treatment could be repeated every 14 days, with at least two courses and up to six courses described. For the group without prior HSCT, the dose was to be assigned at study entry. The corresponding dose statement for the post-HSCT group is cut off, so its details are not reported in the registry record.

Because treatment allocation was non-randomized and the study was single-group, the HSCT categories should not be interpreted as randomized treatment arms or as a control-versus-treatment comparison. Prior transplant history defines the categories, and no untreated or standard-treatment comparator is listed. The registry dates the study start to 2014-03-26 and primary completion to 2014-07-28. Those dates and the terminated status describe the record, but do not establish why the study ended or whether every planned assessment was completed.

The primary outcome is a participant count for DLTs during the first two courses. Secondary outcomes listed include MRD decrease, GVHD and graft failure in participants with prior HSCT, changes in leukemia-cell markers related to immunogenicity and apoptosis, and duration of remission. The record does not report results for these secondary outcomes. The primary endpoint result is also not reported in the registry record, limiting assessment of the study’s principal safety question.

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 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Immunomodulatory molecules were examined at two time points. Analyses were limited to the pretreatment and first post treatment samples. Additional samples were excluded from the analysis. A paired t-test was performed to examine the effect of first treatment on the expression of each gene in the CodeSet. Significance was declared at a nominal p-value threshold of 0.05. We note that this liberal p-value threshold was chosen due to the limited sample size.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The total number of enrolled subjects were 3. One HSCT patient enrolled on dose level #1, and two non-HSCT patients enrolled onto dose level #1.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Dose Limiting Toxicity (DLT) in the First Two Courses of Therapy, measured over Beginning with the first dose of GNKG168 until the end of course 2; courses are 14 days so there will be approximately 28 days of monitoring for DLT.

The primary endpoint is the number of participants with a dose-limiting toxicity during the first two courses of GNKG168. The stated monitoring begins with the first dose and continues until the end of course two, approximately 28 days. In a phase I study, a DLT endpoint is used to describe treatment-limiting toxicity within a specified early-treatment window. It is a safety measure, not a direct measure of antileukemic benefit.

The registry’s definition covers specified non-hematologic toxicities at CTCAE grade 3 or higher when at least possibly related to GNKG168, with listed exceptions. These exceptions include fatigue, fever, and anorexia at grade 3; rash that improves to grade 2 or lower within seven days; and certain liver or enzyme elevations that return to grade 2 or lower within 14 days. The definition also includes grade 3 or 4 hematologic toxicity that is at least possibly related and does not return to baseline within seven days. For participants with prior HSCT, specified GVHD events, bronchiolitis obliterans, and graft failure also qualify.

These criteria make the endpoint dependent on severity, timing, recovery, relatedness assessment, and transplant history. A participant count would indicate how many met the definition, but would not by itself describe each event’s course or establish causation. The registry record does not report the count of participants with DLT, event-level details for this endpoint, or an uncertainty interval. It therefore does not permit an estimate of the observed DLT frequency from the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported design is non-randomized and single-group, with the participant categories organized by history of HSCT. This matters because statistical comparisons between groups are most informative when the groups are comparable in the ways relevant to the question. Random allocation can help balance measured and unmeasured characteristics, whereas grouping participants by transplant history does not do so. General statistical interpretation: a contrast between such groups can reflect differences in participant history or other factors as well as any differences in treatment exposure. The registry record does not report an adjusted comparative analysis.

What does a count endpoint describe?

The primary endpoint is a count of participants who meet the DLT definition during the first two courses. A count is a direct summary of observed participants, not a model-based estimate of how often toxicity would occur in a broader population. When the number of participants is small, each participant’s outcome has substantial influence on the summary. General statistical explanation: an uncertainty interval around a rate can communicate how much the observed data leave open about the underlying rate. No such interval for the primary endpoint is reported in the registry record, and the endpoint count itself is not reported.

DLT classification is not simply a count of every medical event. The definition uses toxicity grade, possible relationship to GNKG168, duration or recovery, and—in participants with prior HSCT—specified transplant-related events. This makes the endpoint clinically structured, but also means interpretation depends on how events were assessed and classified. The registry record gives the criteria but does not report participant-level adjudication or details about how uncertain relatedness assessments were handled.

How should the safety categories be read?

The adverse-event fields report participants at risk and affected, separately for serious and other adverse events, within listed HSCT and dose-level groups. Read each count within its stated group and event category. The figures do not give a randomized comparison. Nor should serious adverse events, other adverse events, and DLTs be assumed to be identical sets of events: the DLT definition has its own criteria and time window. The record does not report a direct reconciliation of the safety categories with the DLT endpoint.

General statistical explanation: event counts can be informative for describing what was observed, but a percentage or count does not show precision on its own. Precision depends on the amount of information, including the number of participants observed and the way events were collected. In this study the enrollment was four, and the record does not report confidence intervals for the posted safety figures. The serious adverse-event summary includes febrile neutropenia at 50.0%, but further denominator details are not reported in the registry record.

What does the biomarker analysis description indicate?

The registry text also describes examining immunomodulatory molecules at pretreatment and first post-treatment time points. It says the analysis was limited to those samples, that additional samples were excluded, and that a paired t-test was performed to examine the effect of first treatment on expression of each gene. The description is truncated, so the complete population or analysis details are not reported in the registry record. No gene-level results, estimates, p-values, or uncertainty intervals are included in the registry record for this analysis.

General statistical explanation: a paired t-test assesses the average within-participant difference between paired measurements, using the fact that the two measurements come from the same participant. It relies on assumptions about the distribution of those differences and can be sensitive to very small sample sizes. A paired analysis is distinct from the binary participant-count endpoint for DLT; its existence does not provide the missing primary endpoint result. The registry record does not report diagnostic checks or additional details of this analysis.

What can be said about planning?

The stated sample-size assumptions describe a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it uses participants per arm. These are planning assumptions, not observed study results or an account of the trial’s own design justification. In particular, the actual study is described as single-group and non-randomized. The sample-size justification, protocol-based power calculation, and intended interim analyses are not reported in the registry record.

General statistical explanation: power is a design property under specified assumptions about an effect, variability, sample size, and analysis. A planning illustration cannot establish the probability that this completed study detected an effect, and it should not be described as observed power. The registry record does not report enough primary-outcome information to evaluate the sensitivity of this trial to a particular DLT rate or treatment effect.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Post HSCT- Dose Level 1", "No HSCT- Dose Level 1")
n      <- c(1, 2)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Post HSCT- Dose Level 1  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  No HSCT- Dose Level 1  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary DLT endpoint and several secondary outcomes: decrease in MRD, GVHD and graft failure among participants with prior HSCT, changes in leukemia-cell markers associated with immunogenicity and apoptosis, and duration of remission. These outcomes concern different measures and, in some cases, different participant subsets. The registry record does not report a statistical plan for controlling multiplicity across these outcomes, nor does it state whether any outcome was designated exploratory beyond its listing as secondary.

General statistical explanation: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiple testing. The appropriate approach depends on the purpose and structure of the analyses. Without a reported multiplicity strategy, any individual secondary finding would need cautious interpretation. The registry entries do not include secondary-outcome results, so there is no basis to assess their statistical significance or consistency.

Missing-data handling and analysis populations are also not reported in the registry record. The biomarker description states that additional samples beyond pretreatment and the first post-treatment sample were excluded from analysis, but it does not explain why those samples were excluded, how missing paired measurements were handled, or how many participants contributed to each gene analysis. The record does not specify whether the primary endpoint analysis used all enrolled participants, participants who received treatment, or another defined population. The number of participants with evaluable DLT data is not reported.

These omissions matter because incomplete outcome availability can affect both the size and composition of the analyzed group. General statistical explanation: an analysis restricted to participants with complete measurements may differ from an analysis of all enrolled participants if missingness is related to health status, treatment exposure, or outcome. No assumption about the reason for missingness can be made from the registry information. The primary endpoint result, missing-data rules, and analysis-population definitions are not reported in the registry record.

12. 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: febrile neutropenia (50.0%).

The serious adverse-event entries are organized by HSCT history and dose level, with counts for participants at risk and affected. For HSCT-Dose Level 1, one participant was at risk and zero were affected for serious adverse events. For No HSCT-Dose Level 1, two were at risk and one was affected. The other listed dose-level groups contain zero counts in these fields. The record lists zero deaths in every group.

For other adverse events, the HSCT-Dose Level 1 entry lists one participant at risk and zero affected; the No HSCT-Dose Level 1 entry lists two at risk and two affected. The remaining listed groups have zero counts in those fields. These are descriptive counts within the registry’s categories. The study enrolled four participants overall, but the registry does not provide a participant-level account explaining how each safety entry relates to the primary DLT endpoint.

Febrile neutropenia is the serious adverse-event term reported with 50.0%. The denominator and the relationship of this summary to individual dose-level groups are not reported in the registry record. The percentage should therefore be read as the registry’s displayed summary, not as a value to recalculate or assign to a subgroup. General statistical interpretation: safety counts from a small study describe events observed during the study; they do not establish the absence of unobserved risks or provide a precise estimate of event frequency.

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

The record establishes that GNKG168 was studied in a phase I, non-randomized, single-group trial involving four enrolled participants with relapsed ALL or AML. The brief summary further describes patients in morphologic remission who were MRD-positive. It specifies an early-treatment safety endpoint based on DLTs during the first two courses, with a monitoring period of approximately 28 days. The primary endpoint result, however, is not reported in the registry record.

The posted safety entries show limited participant counts in the listed dose-level categories, and the record reports zero deaths in each category. They also identify febrile neutropenia as the prominent serious adverse-event term, with 50.0% shown. Those figures are descriptive. They do not show whether an event met the separate DLT criteria, how the primary endpoint was resolved, or how precisely an event frequency can be estimated. The incomplete denominator context for the serious-event percentage further limits interpretation.

The study does not include a randomized control group. Its HSCT categories represent different transplant histories, so contrasts between them cannot isolate a GNKG168 effect. The registry record also does not report comparative efficacy results, a control-group outcome, or enough information to determine the relationship between the posted safety counts and all four enrolled participants.

General statistical interpretation: early-phase safety observations can inform the description of what occurred among participants treated under a study’s conditions, but small samples leave substantial uncertainty about less common events and broader populations. The absence of a posted primary endpoint result is especially important: no conclusion about the observed number of DLTs can be drawn from the information reported. The registry entries do not establish a treatment benefit or lack of benefit, and they do not support a causal comparison with another treatment.

14. Why This Trial Matters Statistically

This trial highlights a basic distinction in early-phase clinical research: a carefully defined endpoint is not the same as a reported endpoint result. The registry gives a detailed DLT definition, including severity thresholds, recovery periods, relatedness, and transplant-specific events. Those details help explain what the study intended to count. Yet the number of participants who met the definition is not reported in the registry record, so the principal safety question cannot be answered from the posted outcome information.

The study also illustrates how design shapes interpretation. A non-randomized, single-group study can describe treatment exposure and observed events, but it does not create a randomized control comparison. Here, the two categories are distinguished by HSCT history. That difference is relevant to the listed transplant-related outcomes, but it also means the categories should not be treated as interchangeable groups for estimating a treatment contrast.

With four participants enrolled, the record contains a very small amount of participant-level experience. General statistical explanation: small studies are often limited in their ability to characterize the frequency and range of events, and their estimates can be highly uncertain. This is not repaired by an assumed power calculation or by a planning illustration based on an observed effect. The planning assumptions listed in the record describe a separate illustration, not the study’s reported rationale or an estimate of what it could reliably detect.

Finally, the record lists secondary outcomes spanning MRD, transplant complications, leukemia-cell markers, and remission duration, but their results and key analysis details are not reported. This makes the trial a useful example of why design, endpoint definitions, data availability, and reporting completeness must be considered together. An endpoint definition can be informative even when a result is unavailable, but it cannot substitute for that result.

15. 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 primary DLT count is not reported in the registry record. Although the endpoint definition and monitoring window are specified, the central observed safety outcome cannot be evaluated. No uncertainty interval or inferential result for that endpoint is reported either.

Enrollment was four, limiting the amount of observed participant-level information. The registry does not report how many participants had each leukemia type, how many had prior HSCT, or how many contributed evaluable data to each outcome. Adverse-event figures are divided into HSCT and dose-level categories, but the registry entries do not explain how those entries map to the enrolled participants overall. The record reports zero deaths in each listed category, but this does not resolve the missing DLT result or establish the absence of other risks.

The design was non-randomized and single-group, with no control intervention listed. Differences between participants with and without prior HSCT cannot be interpreted as randomized treatment effects. The record does not report an adjusted analysis that could address differences between these groups. In addition, the post-HSCT arm description ends before its dose information is complete, so the dosing details for that group are not reported in the registry record.

Further limitations concern analysis and reporting. The reason for termination is not reported. Sample-size justification, interim analyses, missing-data rules, and analysis-population definitions are not reported. The biomarker analysis description is truncated and reports exclusions of additional samples without explaining the reasons or the number of evaluable paired observations. Results for the listed secondary outcomes are not reported in the registry record. These gaps prevent a fuller assessment of endpoint completeness, analysis choices, and the precision of the findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia — NCT01743807.
• Registry record last updated 2025-01-27; status last verified 2024-12.
• Results first posted 2025-01-27.
• 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.

19. Record Summary

NCT01743807 is a phase I study of GNKG168 in pediatric patients with ALL or AML. The registry describes relapsed and refractory disease, with patients in morphologic remission but positive for MRD. The study was non-randomized and single-group, enrolled four participants, and is listed as terminated. Its start date is 2014-03-26, and its primary completion date is 2014-07-28.

The primary endpoint was the number of participants with DLT during the first two courses, monitored from the first dose through approximately 28 days. The DLT result is not reported in the registry record. Posted adverse-event counts are organized by HSCT history and dose level; febrile neutropenia is listed as the serious adverse-event term with 50.0%, and deaths are recorded as zero in each listed group. Secondary outcomes include MRD, transplant-related events, cell markers, and remission duration, but their results are not reported in the registry record. The registry does not report the reason for termination, a control-group comparison, or key details of missing-data and analysis-population handling.