Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies (NCT02120157), a na phase 2 study. The primary outcome is Cumulative Incidence of Non-relapse Mortality.

2. Clinical Question

The clinical question is therefore an estimation question within one treated group, rather than a direct comparison of two treatment strategies. The primary endpoint focuses on death not attributed to relapse during the period ending at Day 180. This is distinct from overall survival, which counts deaths regardless of cause, and from relapse itself.

The registry identifies the study as phase II and reports enrollment of 35. Its stated objective is to estimate the Day 180 incidence of non-relapse mortality after myeloablative HLA-mismatched bone marrow transplantation. The record does not report the observed primary endpoint result, its uncertainty, or an analysis comparing the observed incidence with the stated hypothesis. Consequently, the clinical question is clear, but its answer cannot be determined from the posted results in this record.

3. Trial Design

NCT02120157 is listed as a phase II, multi-institutional study of myeloablative haploidentical bone marrow transplantation with PTCy for pediatric patients with hematologic malignancies. The registry describes a single-group model, with allocation listed as not applicable and masking listed as none. Enrollment is reported as 35, and the study status is completed. The recorded start date is 2015-07-02 and primary completion date is 2018-06-15.

The intervention group is titled “Haploidentical BMT with PTCy for acute leukemias and MDS.” The listed interventions include cyclophosphamide, TBI, busulfan, unmanipulated bone marrow, tacrolimus, and mycophenolate mofetil. The summary says that conditioning was TBI-based for lymphoid leukemia and busulfan-based for myeloid leukemia. The arm description gives some regimen details for patients with AML and MDS and begins a description for ALL and lymphoblastic lymphoma, but the full regimen details are not reported in the registry record.

With no concurrent control group, the design can describe outcomes in the study group but does not provide a randomized comparison with matched related or unrelated transplantation. The summary states a goal of establishing an exportable, inexpensive platform with a safety profile equivalent to those transplant approaches; that stated goal is not itself evidence of equivalence. The registry record does not report a comparator, a prespecified equivalence margin, or an equivalence analysis.

The registry lists several secondary outcomes, including donor cell engraftment, acute and chronic GVHD, graft failure, immunosuppressant use and duration, and survival. It lists 12 outcome measures overall. The registry record does not report analysis entries for these outcomes. The design description therefore establishes what the study intended to investigate, but the posted record does not supply a set of outcome estimates with which to assess those aims.

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.

Before assignment: Three patients screen failed due to: One patient could not report on whether the marrow is cellular or at least 20 percent cellularity, one patient had poor liver function, and the one patient's Alanine aminotransferase (ALT) was over the study limit.

Overall Study

Reasons for not completing this period:

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 Cumulative Incidence of Non-relapse Mortality, measured over Day 180.

The primary endpoint is the cumulative incidence of non-relapse mortality at Day 180, expressed as a percentage. The registry description specifies that it concerns non-relapse mortality within 180 days following myeloablative, HLA-mismatched bone marrow transplantation in patients with high-risk hematologic malignancies. The study summary also refers to the endpoint as 6-month non-relapse mortality and states a hypothesis that it would be < 18%.

Non-relapse mortality distinguishes deaths not attributed to relapse from deaths following a disease relapse. General statistical explanation: when relapse can occur before a non-relapse death, it may prevent the endpoint from occurring in the same way and is treated as a competing event in a cumulative-incidence framework. Cumulative incidence is intended to describe the probability of the event of interest over time while accounting for such competing events. The statistical method used to estimate this endpoint is not reported in the registry record.

This endpoint is useful for describing early mortality not attributed to relapse after transplantation, a period-specific question relevant to the study’s stated safety objective. It is not interchangeable with overall survival or with a count of all deaths. The registry record does not report the observed cumulative-incidence estimate, a confidence interval, or the event count for this endpoint. It therefore does not show whether the stated hypothesis was supported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a clinical endpoint needs a clear event definition, a time horizon, and a population under study. Here, the registry identifies non-relapse mortality as the event of interest and Day 180 as the time horizon. The record does not give the observed endpoint estimate or the details of the analysis population. Those omissions limit interpretation even though the research question is stated.

What does cumulative incidence describe?

General statistical explanation: cumulative incidence describes the probability of an event occurring by a specified time while allowing for competing events. For non-relapse mortality, relapse matters because it can occur before a non-relapse death and change the opportunity to observe that endpoint. This differs from simply calculating the proportion of all enrolled participants who had the event, especially when follow-up lengths vary or competing events occur. The registry names the cumulative-incidence endpoint but does not report which estimator or competing-risk method was used.

A complete report would ordinarily make clear how the endpoint and competing events were defined, how censoring was handled, and which participants contributed to the estimate. Those analysis details are not reported in the registry record. No estimate, confidence interval, or event count for the primary endpoint is posted, so the precision and stability of the estimate cannot be assessed.

How should the hypothesis be read?

The summary states a hypothesis that 6-month non-relapse mortality is < 18%. This identifies a target for the study’s primary objective, but a hypothesis is not an observed result. Evaluating it would require the endpoint estimate and information about its uncertainty and the planned decision rule. The registry record does not report a statistical test, confidence interval, decision threshold beyond the stated hypothesis, or analysis plan. It is therefore not possible to say whether the hypothesis was met.

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrow interval would indicate greater precision than a wide interval, but neither its width nor its position relative to a target can be inferred from enrollment alone. No confidence interval for the primary endpoint is reported.

What does the single-group design allow?

The registry lists a single-group model and no random allocation. A single-group study can estimate outcome frequency in its enrolled participants, subject to follow-up and analysis methods. It cannot, by itself, establish how outcomes would have differed under another transplant approach. Comparisons with external populations would be vulnerable to differences in eligibility, disease characteristics, clinical practice, follow-up, and outcome definitions. The registry record does not identify a concurrent control group or an adjusted comparative analysis.

General statistical explanation: randomization helps balance measured and unmeasured prognostic factors between assigned groups on average. Since this study is not randomized between treatments, its design is not suited to the same causal comparison as a randomized controlled trial. This does not prevent useful description of outcomes; it defines the kinds of conclusions that the design can support.

What can be learned from the safety counts?

Counts of participants affected by adverse events are descriptive. They do not necessarily equal event counts, because one participant may experience multiple events. They also do not establish event timing, duration, severity beyond the category recorded, or causal attribution. The record lists 32 participants at risk and 14 affected for serious adverse events, and 32 at risk and 13 affected for other adverse events. It does not provide the adverse-event analysis methods or enough detail to reconstruct exposure time or account for multiple events per participant.

The listed percentages for serious-event terms are reported values, not comparative estimates. Without a control group and consistent information on ascertainment and follow-up, they should not be interpreted as evidence that one treatment has a higher or lower risk than another. The record’s listed deaths also cannot be equated with the primary endpoint because cause and timing relative to relapse and Day 180 are not reported for these deaths.

What is known about the analysis plan?

The registry record lists 12 outcome measures but no analysis entries. It does not report a statistical analysis plan, sample-size justification, interim analyses, missing-data procedures, or analysis populations. The assumptions described for a planning illustration are not the same as the trial’s own design or observed evidence; planning sample sizes are not observed power. No planning sample-size results are reported in the registry record. Because analysis details are absent, the posted information supports a careful description of study structure and recorded safety figures, but not a reconstruction of the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, with several secondary topics: donor cell engraftment; acute GVHD grades 2-4 and grades 3-4; chronic GVHD; primary and secondary graft failure; steroid and non-steroid immunosuppressants and their duration; and survival. Survival appears twice in the listed secondary outcomes. The record does not report which outcomes were designated for formal hypothesis testing, how any testing across outcomes was handled, or whether an adjustment for multiple comparisons was planned. The primary endpoint’s place in the stated study objective is clear, but the registry record does not provide a complete testing hierarchy.

Multiplicity is a general statistical concern when many hypotheses are tested: the chance of at least one apparently noteworthy finding can increase if results are interpreted without accounting for the number of tests. This concern is distinct from estimating a prespecified endpoint descriptively. Since no analysis entries are listed, it is not possible to assess whether multiplicity affected any reported conclusions.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not say how participants without complete follow-up were handled, how withdrawals or unavailable endpoint information were addressed, or whether analyses used all enrolled participants or a defined subset. Enrollment of 35 does not establish the denominator for each outcome. In particular, the primary endpoint’s number at risk and analyzed population are not stated.

These reporting gaps matter because estimates depend on who is included and how incomplete follow-up is treated. The registry record does not provide enough information to assess potential bias from missing observations, verify the denominators for outcome estimates, or determine whether outcome-specific analyses followed a prespecified plan. No estimate of the primary endpoint is posted, so these issues cannot be resolved by examining its result.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: veno-occlusive disease/ hepatic sinusoidal obstruction syndrome (12.5%), fever (9.4%), graft failure (9.4%), acute gvhd (3.1%), broviac cather infection (3.1%).

The registry reports one intervention group for safety. For serious adverse events, 32 participants are listed as at risk and 14 as affected. For other adverse events, 32 are listed at risk and 13 affected. The record separately lists 8 deaths. These are distinct registry entries, and the record does not establish that the deaths are included in a particular endpoint category or that they occurred by Day 180.

Among the listed serious adverse-event terms, veno-occlusive disease/hepatic sinusoidal obstruction syndrome is reported at 12.5%, fever at 9.4%, graft failure at 9.4%, acute GVHD at 3.1%, Broviac Cather Infection at 3.1%, and intracranial hemorrhage at 3.1%. These figures should be read as the registry’s descriptive entries. The record does not report event definitions, timing, follow-up duration, causal attribution, or whether a participant could contribute to more than one term. The denominator underlying each listed percentage is not specified in the posted safety information.

These counts and terms do not provide a comparison with another treatment group. They also do not answer the primary question about non-relapse mortality at Day 180. A reader should distinguish participants affected by adverse events from the number of events, and distinguish listed deaths from deaths meeting the primary endpoint definition.

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

The registry record establishes that NCT02120157 was a completed phase II, single-group study with enrollment of 35, focused on myeloablative haploidentical bone marrow transplantation with PTCy in pediatric patients with hematologic malignancies. It states a primary objective of estimating cumulative non-relapse mortality at Day 180 and a hypothesis that the incidence would be < 18%. It also lists several transplant-related secondary outcomes and safety information.

What the record does not establish is the observed value of the primary endpoint. No Day 180 estimate, endpoint event count, confidence interval, or test result is posted. The listed deaths cannot be assumed to represent non-relapse mortality by Day 180, because their timing and cause are not reported in relation to the endpoint definition. Accordingly, the record does not show whether the stated hypothesis was supported.

Even a complete estimate from this single-group study would primarily describe outcomes among the participants studied. Without a concurrent comparison group, it would not by itself show that the approach caused a particular outcome or was equivalent to matched related or unrelated transplantation. Equivalence requires an explicit comparative design and an appropriate margin and analysis; those are not reported in the registry record.

The adverse-event entries offer descriptive information, but they do not quantify comparative risk or fully characterize event timing and attribution. The counts affected, the listed percentages for event terms, and the separate death count should not be combined into a conclusion about overall benefit or harm without further definitions and analysis information. In statistical terms, the record supports statements about the study’s aims, design, enrollment, and selected reported safety entries. It does not support a conclusion about the magnitude or precision of the primary endpoint, or a comparative treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is framed as estimation of a time-specific safety outcome in a single group. The endpoint is cumulative non-relapse mortality at Day 180, rather than an unrestricted count of deaths or a comparison of treatment groups. That distinction makes the definition of relapse as a competing event, the follow-up window, and the analysis population important to interpretation.

The study also illustrates a gap between a clearly stated objective and the information needed to evaluate it. The registry gives the objective and the hypothesis of < 18%, but does not report the endpoint estimate or its uncertainty. Without those results, neither the event frequency nor the precision of the estimate can be assessed. Enrollment alone does not provide that information.

The single-group design shapes the scope of inference. It can describe outcomes among participants who received the study approach, but cannot provide a randomized estimate of how those outcomes compare with another transplant strategy. The summary’s stated ambition to establish a platform with a safety profile equivalent to other approaches is therefore a goal, not a demonstrated statistical result in the registry record.

Finally, multiple secondary outcomes and safety categories make transparent outcome definitions and analysis methods valuable. The record lists 12 outcome measures but no analyses, and does not report how missing data or multiplicity were handled. These limitations do not erase the study’s descriptive purpose; they clarify which statistical questions the posted information can answer and which remain unresolved.

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 for statistical interpretation is that the registry record does not report the primary endpoint result. There is no Day 180 non-relapse mortality estimate, confidence interval, event count, or test result. The stated hypothesis therefore cannot be assessed from the posted information.

The record also does not report the primary analysis population, the number at risk at Day 180, endpoint-specific follow-up, or methods for censoring and competing events. Although the endpoint is described as cumulative incidence, the estimator and handling of relapse are not specified. The number enrolled cannot replace these details or establish the denominator used for the primary analysis.

The single-group design has no concurrent comparator, and the record lists allocation as not applicable. It therefore cannot support a randomized comparison or establish equivalence to other transplant approaches. The registry does not report an equivalence margin or comparative analysis. The safety entries are also limited: definitions, event timing, attribution, and the denominators for listed percentages are not reported. The record does not clarify how the 8 deaths relate to non-relapse mortality or to the Day 180 window.

Further limitations include the absence of analysis entries despite 12 listed outcome measures. Statistical methods, missing-data handling, multiplicity procedures, interim analyses, and the trial’s sample-size justification are not reported in the registry record. The description of the arm regimen is incomplete for some patients, and the full protocol details are not reported. These gaps restrict assessment of outcome ascertainment, analytic choices, and the extent to which posted safety results address the study’s stated objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies — NCT02120157.
• Registry record last updated 2021-11-26; status last verified 2021-11.
• Results first posted 2019-04-18.
• 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

NCT02120157 is listed as a completed phase II, multi-institutional, single-group study of myeloablative haploidentical bone marrow transplantation with PTCy for pediatric patients with hematologic malignancies. The registry reports enrollment of 35, a start date of 2015-07-02, and a primary completion date of 2018-06-15.

The primary endpoint is cumulative incidence of non-relapse mortality at Day 180. The study summary states a hypothesis that 6-month non-relapse mortality would be < 18%. The registry lists 12 outcome measures and no analysis entries. It does not report the primary endpoint estimate or its uncertainty.

Safety entries include 32 participants at risk and 14 affected for serious adverse events, 32 at risk and 13 affected for other adverse events, and 8 deaths. These entries are descriptive and do not establish the Day 180 primary endpoint result or a comparative treatment effect.