Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath (NCT00580034), a non-randomized phase 2 study. The primary outcome is Toxicity.

2. Clinical Question

This question is narrower than asking about toxicity among everyone enrolled or everyone receiving a transplant. The primary outcome population is defined by DLI receipt, and follow-up for evaluability begins at the first DLI. DLI doses are described as ranging from 1×104 CD3+ cells/kg to 3.27 ×108 CD3+ cells/kg. The registry states that results are not exclusive, so outcome categories should not be assumed to be mutually exclusive.

The study’s stated purpose was long-term follow-up after allogeneic transplantation. Its brief description discusses engraftment and graft-versus-host disease as issues addressed in earlier work, but it does not report a comparative clinical effect for this study. The statistical question that can be addressed from the posted record is therefore descriptive: what toxicity data were collected, in whom, and over what period? A treatment effect relative to another approach cannot be estimated from the single-group design.

3. Trial Design

This is a Phase 2, completed, non-randomized, single-group study with no masking. The registry lists enrollment of 176. The study began in 2003-02, and primary completion is recorded as 2013-04. The listed conditions are lymphoma, myeloma, leukemia, myelodysplasia, and solid tumors. These enrollment and design details describe the study as a whole; they do not identify the number of participants included in the primary toxicity analysis.

The intervention is named Campath Purged Non-myeloablative ASCT. The arm description identifies a Campath-purged non-myeloablative allogeneic stem cell transplant for the listed malignancies and marrow failure. Donor Apheresis is also listed as an intervention. The donor description specifies a sibling, half sibling, parent, child, or first cousin familial relationship and a 3-5/6 human leukocyte antigen match. Further donor eligibility wording is incomplete in the registry record, so additional eligibility details are not reported in the registry record.

Because the study has a single group and is not randomized, it does not assign participants to competing treatment strategies. There is no like-for-like control comparison. The design can describe outcomes observed in the enrolled study population, but it cannot by itself separate treatment effects from changes over time, participant characteristics, or other influences. No masking also means that blinding is not part of the listed design.

The primary outcome is titled Toxicity and has a timeframe of 1 year. Its analysis population is not all enrolled participants: it is the cohort who received at least one DLI, with evaluability beginning on the first DLI date. The registry says acute graft-versus-host disease (GVHD) was graded according to consensus criteria and that Common Terminology Criteria (CTC) v3.0 was used for other toxicities. It also describes formal recording twice weekly for the first 100 days, at follow-up visits, and as needed between visits. The primary endpoint result and the number included in that endpoint analysis 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.

Before assignment: Prior to selecting a donor: donor and subjects had history and physical exam, labs and chest x-ray performed per program and FACT requirements. Female donors should have a negative pregnancy test. Subjects also had bone marrow. Prior to treatment, disease progression and insurance denial led to removal from the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Cohort of subjects on the study who received \>/=1 donor lymphocyte infusion (DLI). DLI doses thus ranged from 1×104 CD3+ cells/kg to 3.27 ×108 CD3+ cells/kg. Subjects were considered evaluable from the day of first donor lymphocyte (DLI) infusion. Results are not exclusive.

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: Cohort of patients who actually received at least 1 donor lymphocyte infusion (DLI). DLI dosages thus ranged from 1×104 CD3+ cells/kg to 3.27 ×108 CD3+ cells/kg.

6. Primary Endpoint

The registry lists the primary outcome as Toxicity, measured over 1 year.

The primary outcome is titled Toxicity, is measured in participants, and has a 1 year timeframe. Its description combines acute GVHD with other toxicities: acute GVHD was graded according to consensus criteria, while CTC v3.0 was used for all other toxicities. The registry treated skin, gut, and liver toxicity consistent with acute GVHD as acute GVHD if it occurred at any time during the year following infusion. This extended window reflects the registry’s stated recognition that acute GVHD pathology in the non-ablative and DLI setting may occur late.

The outcome population is specifically the study cohort that received at least one DLI. Participants were considered evaluable from the date of their first DLI, rather than from enrollment or transplant, and the listed DLI doses span a broad range. The registry says the results are not exclusive; accordingly, a participant could potentially contribute to more than one toxicity category, and category counts should not be treated as disjoint without further information.

Recording toxicity over time is useful for describing the types and occurrence of safety events during follow-up. The registry says toxicities were formally recorded twice weekly for the first 100 days, at each follow-up visit, and as needed between visits. However, the record does not report the primary endpoint’s observed count, category-specific results, or analysis denominator. It therefore does not support a numerical estimate of primary toxicity frequency or precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several design and analysis concepts help clarify what the registry can and cannot establish. They are general statistical explanations, not claims that a particular unreported method was used.

What does a single-group design tell us?

A single-group study records outcomes in participants receiving the study approach without a separate control group. It can describe which events were observed and how often they were recorded when those results are reported. It does not provide a direct estimate of the contrast between the study approach and another treatment. In a randomized comparison, random assignment is intended to make groups comparable on average with respect to factors known and unknown at the start. This study is listed as non-randomized and single-group, so that randomized comparison is absent. No comparator-group outcome is reported in the registry record.

The absence of a control group matters even when an event is clearly defined and follow-up is carefully conducted. Events can arise from the underlying disease, other care, or the treatment setting, and a single-group record cannot by itself distinguish among those explanations. The result should therefore be described as an outcome observed in the study cohort, not as an effect attributable to the intervention.

Why define the analysis population?

The primary outcome is not described for every enrolled participant. It applies to the cohort that received at least one DLI, with evaluability starting on the date of the first DLI. This choice defines both who contributes to the endpoint and the point from which its timeframe is measured. It differs from starting follow-up at enrollment or transplantation. The number of participants meeting this endpoint definition is not reported in the registry record, so the overall enrollment cannot be substituted as the endpoint denominator.

The stated primary timeframe is 1 year following infusion. The registry’s approach to acute GVHD includes qualifying skin, gut, and liver toxicity occurring at any time in that year, in recognition that onset may be late in this setting. A timeframe is important because event counts depend on how long participants are observed and which events qualify. The record describes follow-up and recording practices, but does not provide individual follow-up completeness or the endpoint analysis denominator.

How should event counts and categories be read?

A participant count is a count of people meeting an event definition; it is not necessarily a count of separate event episodes. A person may experience more than one event or meet more than one toxicity category. The registry explicitly states that results are not exclusive. Therefore, category counts should not be summed or treated as mutually exclusive. A clear report would ordinarily distinguish participants with at least one event from the number of event occurrences, define each category, and state its denominator. The primary outcome result is not reported, and the adverse-event listing does not provide all of these details.

The registry uses consensus criteria for acute GVHD and CTC v3.0 for other toxicities. Standardized criteria can support consistent classification, but interpretation still depends on how categories were applied, whether assessments were complete, and how borderline or overlapping events were handled. The registry describes formal assessments twice weekly for the first 100 days, at each follow-up visit, and as needed intercurrently. It does not report assessor agreement, adjudication procedures, or completeness of those assessments.

What does uncertainty mean?

In general, a confidence interval expresses the uncertainty around an estimate: narrower intervals indicate greater precision, while wider intervals indicate less precision. An interval does not remove limitations in design, and it does not establish causation. The registry record does not report confidence intervals for the primary outcome or the adverse-event summaries. Since the primary outcome count is also absent, its magnitude and precision cannot be assessed from this record.

In general, event proportions are sensitive to both the number of events and the denominator. A denominator should match the outcome’s population and observation window. For example, the 88 participants at risk in the adverse-event listing cannot be presumed to be the same as the DLI-defined population for the primary toxicity outcome. That relationship is not reported in the registry record.

What can planning illustrations establish?

The study record describes sample-size assumptions for planning illustrations: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Those are planning assumptions, not evidence that the study randomized participants or used a two-arm design. The actual trial is listed as single-group and non-randomized. The record does not report the observed primary effect or a numerical planning result, so no such illustration can be interpreted as a trial finding. Any sample size derived from an assumed effect is a planning illustration, not observed power.

The record lists zero analyses. It does not report a statistical analysis plan, adjustment method, model for the primary endpoint, handling of repeated events, interim analyses, or a sample-size justification. Those methods should not be inferred from the endpoint definitions or from the planning assumptions. The registry’s described monitoring schedule and toxicity grading standards are useful methodological details, but they do not substitute for a reported analysis method or outcome estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies Response as a secondary outcome. It also lists zero analyses. Results for the secondary outcome and detailed results for the other outcome measures are not reported in the registry record. A statistical plan specifying which outcomes were primary for inference, how multiple outcomes would be handled, or whether any adjustment for multiple comparisons was intended is not reported in the registry record.

In general, examining multiple outcomes can increase the chance of finding an apparently notable result by chance, especially when many tests are conducted. Methods for addressing multiplicity can include defining a single primary outcome, adjusting significance thresholds, or presenting analyses as exploratory. Those are general approaches; the record does not state which, if any, was planned or used. Since no analyses are listed, there is no reported multiplicity adjustment to interpret.

Missing-data procedures are also not reported in the registry record. The description gives a schedule for recording toxicities—twice weekly during the first 100 days, at follow-up visits, and as needed—but does not state how missed visits, incomplete records, withdrawal, or loss to follow-up were handled. It does not report the amount or pattern of missing outcome data. In general, missingness can affect both the denominator and the interpretation of an event proportion, particularly if participants with incomplete follow-up differ from those fully observed.

The primary analysis population is defined as study participants receiving at least one DLI, evaluable from their first DLI. Whether all eligible participants contributed complete follow-up, whether analyses followed another population definition, and how participants with partial observation were treated are not reported in the registry record. The overall enrollment of 176 should not be treated as the denominator for this endpoint without a reported connection between enrollment and the DLI-based analysis population.

11. Safety Results

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

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: death (80.7%), hemorrhage (13.6%).

The registry lists one adverse-event group, Campath Purged Non-myeloablative ASCT. For serious adverse events, it reports 75 affected among 88 at risk; for other adverse events, it reports 71 affected among 88 at risk. These are the posted group summaries. They should not be assumed to be results for the primary toxicity endpoint, whose population is defined by receipt of at least one DLI and whose result is not reported in the registry record.

The listed top serious adverse event terms are Death at 80.7% and Hemorrhage at 13.6%. The record does not specify the denominator or counting basis for these percentages. They therefore cannot be interpreted as percentages of all enrolled participants, as risks over a defined follow-up period, or as a direct measure of treatment-attributable harm. A serious-event term is not itself evidence that the event was caused by the intervention.

The registry does not provide event-level definitions, timing, participant overlap, or a comparison group for these figures. Since results are not exclusive, the affected counts across different categories should not be added to estimate a total number of participants. Read the listing as a descriptive safety summary with important details about its denominator and interpretation unreported.

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

The record identifies a completed Phase 2 study of a Campath-purged non-myeloablative allogeneic transplant approach and describes a toxicity assessment in participants who received at least one DLI. It also gives the assessment timeframe and the stated grading and recording procedures. These details define the intended safety question, but the primary toxicity result is not reported in the registry record.

The adverse-event figures describe a listed group, with serious and other event summaries and two prominent serious-event terms. They do not establish a treatment effect. The registry does not provide a comparator, and it does not report the denominator basis for the percentages attached to Death and Hemorrhage. The adverse-event summaries also cannot be assumed to refer to the primary endpoint’s DLI-defined population. These distinctions matter: a number can be accurately quoted while still lacking the information needed to interpret it as a risk or compare it across settings.

In general, observing events in a treated group can be useful for describing what was recorded under the study’s monitoring procedures. It does not show what would have happened to the same participants under another treatment. That counterfactual comparison is not available from a single-group, non-randomized design. Nor does a lack of a reported primary result mean that no toxicity occurred; it means the registry record does not give the endpoint result needed to quantify it.

The posted information therefore supports statements about study design, outcome definitions, and the presence of adverse-event summaries. It does not support a numerical estimate for the primary endpoint, a conclusion about the comparative safety or efficacy of the regimen, or a claim that observed events were caused by the intervention. The registry also does not report uncertainty intervals for the event summaries, so their statistical precision cannot be assessed from the record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why the study population and time origin must be read alongside an outcome label. The primary outcome is not framed for everyone enrolled: it concerns participants who received at least one DLI and begins follow-up at the first DLI. The overall enrollment of 176 therefore does not supply the primary endpoint denominator. Without that endpoint population size and result, even a clearly named outcome cannot be quantified.

The record also distinguishes safety monitoring from statistical evidence of a treatment effect. It describes consensus criteria for acute GVHD, CTC v3.0 for other toxicities, and a schedule of formal toxicity recording. These features clarify how the investigators intended to capture events. They do not replace reported outcome counts, uncertainty estimates, or a comparator. Measurement detail and inferential strength are different parts of a study’s evidence.

The single-group, non-randomized design illustrates a central limitation of descriptive results. Event frequencies may characterize the observed cohort, but a treatment comparison requires a suitable reference group and a defined analysis. Without randomization or a comparator in this registry record, differences from another population could reflect differences in who was studied or how follow-up was conducted.

Finally, the statement that results are not exclusive is important for interpreting toxicity categories. Overlapping categories cannot be treated as independent pieces that can simply be combined into a total. The record’s safety counts and listed terms are best understood as summaries whose denominator and relation to the primary outcome require caution. These design and reporting distinctions are broadly relevant when evaluating safety information from clinical trials.

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 central limitation for interpreting the primary outcome is that its numerical result is not reported in the registry record. The analysis denominator and the number of participants who received at least one DLI are also not reported. Although overall enrollment is listed as 176, it cannot be used as a substitute for the endpoint-specific population.

The study is single-group and non-randomized, with no like-for-like control comparison. This prevents estimation of a randomized treatment contrast and limits causal interpretation of observed outcomes. Masking is listed as none. The record does not report whether outcome assessors were independent or whether event classification was adjudicated.

The primary outcome spans a defined period following first DLI, but completeness of follow-up and handling of participants with partial observation are not reported in the registry record. Nor are missing-data methods, an analysis plan, adjustment procedures, interim analyses, or a sample-size justification reported. The record describes toxicity collection and grading, but does not state how overlapping events were handled beyond noting that results are not exclusive.

The adverse-event listing has its own interpretive limits. The registry reports serious and other affected counts with 88 at risk, but does not establish that this population matches the primary outcome cohort. It also does not explain the denominator for the percentages attached to Death and Hemorrhage. The categories’ time windows and participant overlap are not specified in the listed summary, and no uncertainty estimates are reported.

Finally, the record lists Response as a secondary outcome, but its results and details for the other outcome measures are not reported in the registry record. These omissions mean that conclusions should remain limited to the design and monitoring information and the descriptive adverse-event figures that are explicitly recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath — NCT00580034.
• Registry record last updated 2014-06-03; status last verified 2014-05.
• Results first posted 2014-06-03.
• 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

This completed Phase 2 study is listed as non-randomized, unmasked, and single-group, with enrollment of 176. It studied Campath-purged non-myeloablative allogeneic stem cell transplantation for lymphoma, myeloma, leukemia, myelodysplasia, and solid tumors. The primary outcome is Toxicity over 1 year in participants who received at least one DLI, with evaluability beginning at the first DLI.

The registry describes consensus criteria for acute GVHD, CTC v3.0 for other toxicities, and scheduled toxicity recording. It lists serious adverse events as 75 affected among 88 at risk and other adverse events as 71 affected among 88 at risk. Death at 80.7% and Hemorrhage at 13.6% are listed as top serious adverse event terms, without a reported denominator basis for those percentages.

The primary outcome result, its analysis denominator, and statistical uncertainty estimates are not reported in the registry record. The single-group design supplies no randomized control comparison, so the posted information does not establish a comparative treatment effect.