Check Point Inhibition After Autologous Stem Cell Transplantation in Patients at High Risk of Post Transplant Recurrence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Check Point Inhibition After Autologous Stem Cell Transplantation in Patients at High Risk of Post Transplant Recurrence (NCT02681302), a na phase 1, phase 2 study. The primary outcome is Safety of Combined Check Point Inhibition Therapy Via Assessment of Adverse Events and Lab Findings.

2. Clinical Question

3. Trial Design

NCT02681302 was a Phase Ib-IIA, single-group study sponsored by Hackensack Meridian Health. It addressed checkpoint inhibition after autologous hematopoietic stem cell transplantation for patients at high risk of post-transplant recurrence, including people with multiple myeloma or lymphoma. The registry lists an enrollment of 46 and six clinical cohorts. The reported safety summaries use Group A through Group F; the record does not map these labels to diagnoses or explain how participants were assigned among them.

There was no randomized allocation and no masking. The record does not identify a concurrent control treatment. As a result, the study design does not provide a like-for-like randomized comparison of combined checkpoint inhibition against another treatment or against no checkpoint inhibition. The six groups should not be read as randomized treatment arms.

The intervention was a combination of ipilimumab and nivolumab after transplantation. Ipilimumab was listed at 1 mg/kg for 6 doses at Weeks 1, 4, 7, 10, 16, and 22. Nivolumab was listed at 3 mg/kg for 12 doses at Weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26. The primary safety endpoint had a 26-week timeframe.

The study started on 2016-06-07, had a primary completion date of 2024-05-10, and is listed as terminated. The reason for termination, the timing of the decision, and whether termination followed the specified toxicity rule are not reported in the registry record. Nor does the record explain why the enrollment was 46 or provide a study-specific sample-size justification.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients at high risk for post-transplant recurrence including patients with persistent and recurrent high risk diffuse large B cell lymphoma, high risk and recurrent T cell lymphoma and high risk and recurrent multiple myeloma treated with nivolumab and ipilimumab after autologous hematopoietic stem cell transplantation

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety of Combined Check Point Inhibition Therapy Via Assessment of Adverse Events and Lab Findings, measured over 26 weeks.

The primary endpoint was the number of treatment-related limiting toxicities assessed over 26 weeks. It was intended to capture serious non-hematologic toxicity after combined checkpoint inhibitor treatment began. The definition required at least one treatment-related non-hematologic toxicity of grade 4 or higher under CTCAE. This endpoint focuses on severe toxicity attributed to treatment rather than on every adverse event reported during follow-up.

The protocol description also specifies a group-level stopping rule: a group would be terminated if 3 of 7 patients experienced a treatment-related limiting toxicity. Such a rule is a safety safeguard in a multi-cohort study; it sets a threshold for stopping a group if severe toxicity accumulates. It does not, by itself, establish how the endpoint was observed or adjudicated, and the registry record does not report whether the rule was triggered.

The record names the endpoint and definition but does not post the primary endpoint result, an event count, or an analysis. Adverse-event summaries are present, but they do not identify which events met the primary definition of treatment-related limiting toxicity. The listed serious adverse events therefore cannot be substituted for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help clarify what a study's observations can support. For this trial, the posted record identifies a primary safety endpoint and gives group-level adverse-event counts, but reports no analyses. The points below distinguish general statistical interpretation from information specific to the registry record.

What does a count endpoint describe?

As a general statistical concept, a count endpoint records how many qualifying events or affected participants meet a prespecified definition. The definition matters: a count of all adverse events is not interchangeable with a count of participants who experienced at least one severe, treatment-related event. In this study, the primary endpoint was treatment-related limiting toxicity: at least one treatment-related non-hematologic toxicity of grade 4 or higher after combined treatment began. Its timeframe was 26 weeks.

The posted adverse-event summaries do not identify whether each serious event met all elements of that definition. Seriousness, severity grade, whether an event was non-hematologic, and attribution to treatment are distinct characteristics. The record does not give the primary endpoint count or a participant-level account that would allow the count to be reconstructed from the group summaries.

Why does the single-group design matter?

As a general concept, a single-group study can describe outcomes observed among participants who received the intervention. Without a randomized comparison group, it cannot separate the treatment's contribution from other explanations, such as the underlying illness, transplantation, or other care. Randomization is one way to balance measured and unmeasured factors between groups; that protection is not available in a single-group design.

The registry identifies allocation as NA, masking as none, and the model as single group. The six safety groups are not presented as randomized comparisons. The registry record does not report a comparator or an analysis contrasting the groups, and no treatment effect estimate is posted.

How should uncertainty be considered?

In general, a confidence interval expresses the range of effect estimates compatible with the data and a specified statistical procedure. It helps readers judge precision; an estimate based on limited observations can be uncertain even when it is presented as a single count. No confidence intervals are reported for the adverse-event counts, and the registry does not post a primary endpoint estimate with an interval. Thus, the group counts should be read as descriptive observations, not precise estimates of underlying risk.

Counts also depend on how many participants were observed and for how long. The group summaries report numbers at risk, but the registry does not supply detailed follow-up, censoring, or missing-outcome information for these safety figures. The primary endpoint timeframe is 26 weeks, but the record does not provide a primary endpoint analysis by that timeframe.

What can be inferred from the reported analyses?

The record lists 1 outcome measure and 0 analyses. It identifies the primary safety endpoint but does not post its result, a statistical model, a hypothesis test, a p-value, or an adjusted estimate. There is no basis in the record for describing a statistically significant difference or a treatment effect. The adverse-event figures are counts and percentages as reported, rather than results of a comparative analysis.

As a general principle, a p-value is one measure of how compatible observed data are with a specified null hypothesis and model; it does not measure clinical importance or prove that an effect is absent. No p-value is posted for the primary endpoint. Likewise, absence of a reported analysis is not evidence that there were no events or that groups were equivalent.

What is the role of the group-stopping rule?

The record says a group would be terminated if 3 of 7 patients in that group experienced a treatment-related limiting toxicity. In general, a stopping rule is a prospective safety boundary intended to guide decisions as data accumulate. To judge how it operated, readers would need information about which participants were evaluated, when decisions were made, how events were attributed, and whether the threshold was reached. That information, including whether any group was terminated under this rule, is not reported in the registry record.

The record also does not report interim-analysis methods, a statistical analysis plan, or details of outcome adjudication. These omissions limit evaluation of how the planned safety endpoint was translated into the posted summaries. No additional statistical method should be inferred from the event counts alone.

10. Multiplicity, Missing Data and Analysis Populations

The study description names safety assessment and also says investigators intended to assess complete response and progression-free survival. It further describes monitoring immune reconstitution, phenotype, T-cell receptor repertoire, and the gut microbiome. The registry record does not report analysis results for these additional outcomes or explain how multiple outcomes or cohorts were handled statistically.

Multiplicity is a general statistical concern when several outcomes, groups, or hypotheses are examined. Repeated testing can increase the chance of obtaining apparently notable findings by chance. Statistical plans may address this in different ways, but the registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or another strategy for interpreting multiple tests. Since no analyses are listed, there are no posted hypothesis tests to assess for multiplicity.

Missing-data methods and analysis populations are also not reported in the registry record. It does not specify how participants with incomplete follow-up, discontinuation, or missing endpoint assessments were handled, nor does it define an intention-to-treat, safety, or evaluable population. The at-risk counts in the adverse-event summaries do not, by themselves, explain how those populations were constructed or why the group counts differ.

The record does not state whether interim analyses occurred, whether any stopping decision followed a formal interim review, or what statistical plan governed the analyses. These details should not be inferred from the terminated status or from the group-stopping rule. Without them, interpretation must remain at the level of the posted descriptive safety figures.

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: fever (40.0%), pneumonitis (25.0%), adrenal crisis (20.0%), alanine aminotransferase increased (20.0%), alkaline phosphatase increased (20.0%).

The serious adverse-event summaries report affected participants alongside the number at risk in each group. Group A lists 3 of 7 affected, Group B 5 of 7, Group C 2 of 5, Group D 1 of 4, Group E 4 of 7, and Group F 3 of 5. These counts describe the registry's group-level reporting; they are not the primary endpoint result, which required a treatment-related non-hematologic toxicity of grade 4 or higher.

Other adverse events are listed for 7 of 7 participants in Groups A, B, and E, 5 of 5 in Groups C and F, and 4 of 4 in Group D. Deaths are listed as 0 in Group A, 4 in Group B, 1 in Group C, 3 in Group D, 5 in Group E, and 1 in Group F. The record does not provide attribution or causes for these deaths, so they should not be assumed to be treatment-related.

The listed serious-event terms include Fever at 40.0%, Pneumonitis at 25.0%, and Adrenal Crisis, Alanine Aminotransferase Increased, Alkaline Phosphatase Increased, and Aspartate Aminotransferase Increased at 20.0% each. The denominator and further context for these percentages are not reported in the registry record. Counts and percentages alone do not show event timing, duration, severity grade, or causality.

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

The registry record documents a study of combined ipilimumab and nivolumab after autologous hematopoietic stem cell transplantation in patients at high risk of post-transplant recurrence. Its primary safety question concerned treatment-related limiting toxicity over 26 weeks, with a stated stopping threshold for each group. The adverse-event summaries provide descriptive counts for Groups A through F, and the record lists deaths and selected serious-event terms.

These data do not supply the primary endpoint result. The serious adverse-event counts cannot be treated as the primary endpoint because the registry does not show which events were treatment-related, non-hematologic, and grade 4 or higher. The group-stopping rule is described, but whether it was triggered is not reported. The adverse-event summaries therefore do not establish how many participants met the endpoint definition.

The study was single-group and unmasked, without a randomized comparator. As a general interpretation principle, observations in a single group describe what occurred among enrolled participants, but cannot determine what would have occurred under a different treatment strategy. The counts cannot support a causal comparison or a claim that one treatment is safer than another.

The record also does not report results for complete response or progression-free survival, despite describing these as study interests. It gives no analysis of treatment effect, no uncertainty interval, and no explanation for the terminated status. The registry record therefore supports a limited description of posted safety data, not a conclusion about efficacy, comparative safety, or the reason the study ended.

These limits do not erase the value of the reported observations. They define what can responsibly be concluded from the information available: the listed group counts and terms are descriptive, while the planned primary endpoint and the clinical outcomes remain unevaluated in the posted record.

13. Why This Trial Matters Statistically

This trial raises statistical questions that often arise in early-phase studies of complex treatment settings. The intervention followed autologous hematopoietic stem cell transplantation and combined two checkpoint inhibitors. The intended population included several high-risk or recurrent disease groups, organized into six clinical cohorts. Heterogeneity across diseases and cohorts can matter because a pooled summary may conceal variation in participant characteristics and observed events. The registry record does not report the cohort mapping or an analysis that addresses such variation.

The safety endpoint was defined around a severe, treatment-related toxicity and paired with a stopping rule. This makes clear endpoint definitions and event attribution especially important. A broad serious adverse-event count is not automatically equivalent to the narrower primary endpoint. Distinguishing these measures is essential when interpreting safety reporting.

The single-group design also illustrates the difference between describing outcomes and estimating comparative effects. Counts can document what was reported among participants, but without a randomized comparator they cannot answer how outcomes would differ under another treatment approach. That distinction applies even when the study includes several groups, unless those groups were designed and analyzed as valid comparisons; the registry record does not establish that they were.

Finally, the record lists the trial as terminated but does not give the reason or the primary endpoint result. Statistical transparency depends not only on defining an endpoint in advance, but also on making its observed result, analysis approach, missing-data handling, and decision history available. The missing details constrain interpretation and illustrate why registry descriptions and posted outcome results need to be considered separately.

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 registry record does not report the primary endpoint event count or analysis, despite defining treatment-related limiting toxicity and specifying a 26-week timeframe. It also does not state whether the group-stopping rule was triggered. The serious adverse-event summaries cannot fill this gap because they do not identify event grade, treatment attribution, or whether the events meet the primary endpoint definition.

The record lists a single-group, unmasked design with no randomized comparator. It does not provide a like-for-like control comparison, so the reported safety counts cannot isolate the effect of the intervention from other factors. The mapping of Groups A through F to the six clinical cohorts is not reported, nor is the basis for the differing at-risk counts.

Further limitations are the absence of posted analyses, uncertainty intervals, and details about analysis populations, missing data, or follow-up. The registry record does not report the reason for termination, the timing of that decision, or whether it was related to the safety rule. It also does not provide the denominator or additional context for the percentages attached to selected serious-event terms. Results for complete response and progression-free survival are not reported. These limitations prevent a complete assessment of the planned safety endpoint and the broader clinical outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Check Point Inhibition After Autologous Stem Cell Transplantation in Patients at High Risk of Post Transplant Recurrence — NCT02681302.
• Registry record last updated 2026-04-03; status last verified 2026-03.
• Results first posted 2025-07-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02681302 was a Phase Ib-IIA, single-group study sponsored by Hackensack Meridian Health. It evaluated ipilimumab and nivolumab after autologous hematopoietic stem cell transplantation in patients at high risk of post-transplant recurrence, across six clinical cohorts. The registry lists enrollment of 46, a start date of 2016-06-07, primary completion on 2024-05-10, and status as terminated.

The primary endpoint was treatment-related limiting toxicity over 26 weeks, defined as at least one treatment-related non-hematologic toxicity of grade 4 or higher. The record specifies a group-stopping rule but does not report whether it was met or post the primary endpoint result. It lists serious and other adverse-event counts by Group A through Group F, along with deaths and selected serious-event terms. No analyses are listed, and results for complete response and progression-free survival are not reported. The reason for termination is not reported in the registry record.