Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma (NCT01685606), a na phase 2 study. The primary outcome is Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies..

2. Clinical Question

The study asks whether donor lymphocytes can stimulate an immune response against leukemia or lymphoma. Its stated primary outcome is overall response after infusion, with assessment scheduled at 8 weeks after infusion, then 6 months after, and every 4 months for approximately 2 years. The record provides response criteria for AML and ALL, including complete remission, complete remission with incomplete recovery, and partial remission. It does not specify a separate set of response criteria for each listed lymphoma condition in the primary outcome description.

Because this is a single-group study, the question is descriptive: what responses and safety events were recorded among participants who received the infusion? There is no randomized or concurrent control group with which to distinguish treatment-associated changes from the course of the underlying diseases, other care, or variation in assessment. The posted results do not include primary response analyses, so the response question cannot be answered from the registry results available in this record.

3. Trial Design

This is a phase 2, single-group study sponsored by Brown University. The registry lists enrollment of 6, allocation as NA, and masking as none. The study began in 2013-03, had primary completion in 2015-06, and is marked terminated. The reason for termination is not reported in the registry record.

The intervention is described as cellular immunotherapy. The arm description specifies an infusion of a minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor, irrespective of the number of CD34+ cells. The record does not describe a control intervention. With a single group, participants are not assigned between competing treatment arms, and the design does not support a direct randomized comparison.

The conditions listed span mantle cell lymphoma, diffuse large cell lymphoma, Burkitts lymphoma, T cell lymphomas, and acute myeloid leukemia/acute lymphoblastic leukemia. This breadth matters when interpreting a response endpoint: the diseases differ, and the primary outcome description supplies specific criteria for AML and ALL without detailing corresponding criteria for every listed lymphoma. The registry record does not report condition-specific results or the distribution of participants across diagnoses.

The primary outcome is overall response, recorded as the number of participants, with assessment described at 8 weeks after infusion, then 6 months after and every 4 months for approximately 2 years. A secondary outcome concerns the rate of dose-limiting toxicities of HLA haploidentical peripheral blood phereseed cellular infusions. The record reports two outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, interim analyses, or why the study was terminated.

A single-group design can describe outcomes among treated participants, but it cannot by itself establish how outcomes would have differed under another treatment or no infusion. The absence of masking also means the record does not describe blinded assessment. How response assessments were conducted or reviewed is 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

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 Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies., measured over 8 weeks after infusion then 6 months after and every 4 months for approximately 2 years.

The primary endpoint is the overall response to cellular immune therapy, expressed as the number of participants. The registry describes the assessment schedule as 8 weeks after infusion, then 6 months after and every 4 months for approximately 2 years. It gives detailed criteria for AML and ALL: complete remission requires specified findings in peripheral blood and bone marrow, no extramedullary leukemia, and hematopoietic recovery; complete remission with incomplete recovery allows an ANC or platelet count below the stated recovery threshold; partial remission allows the specified bone marrow blast range while otherwise meeting CR criteria.

Response endpoints are used to summarize whether participants meet prespecified clinical and laboratory criteria after treatment. Counting participants meeting a response category can be a clear descriptive outcome, but it does not indicate how durable responses are unless the analysis also accounts for timing and follow-up. The record does not report how response categories were combined into overall response, how missing assessments were handled, or how repeated assessments were used in the endpoint.

The primary outcome population field is blank, and the results contain no reported response count or rate. Thus, the registry record identifies the endpoint and its timing but does not provide an analyzed estimate of response. It also does not provide a confidence interval or other measure of precision for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study records outcomes among participants receiving the intervention. Its direct statistical output is descriptive: counts, proportions, or other summaries of what happened in the enrolled group. It does not estimate a randomized contrast because there is no concurrent comparison group. In this study, allocation is listed as NA and the model is single group. Accordingly, a response observation, if reported, would describe participants after cellular immunotherapy; it would not show what would have happened to the same participants under another treatment.

Randomization helps make groups comparable on average by assigning treatment independently of participant characteristics. In a single-group study, differences between observed outcomes and what might have occurred without the intervention can reflect disease severity, participant selection, other care, or natural variation. General statistical interpretation therefore distinguishes a treatment-associated observation from a causal treatment effect. The registry record does not include a comparator that would support the latter type of estimate.

What does a count endpoint mean?

The primary outcome is recorded as the number of participants meeting overall response criteria. A count is an absolute number of observed participants, while a response rate expresses that count relative to an analysis denominator. The registry identifies the outcome as a participant count but does not report an observed count, denominator, or response rate. Those quantities should not be inferred from enrollment or from safety fields.

The response criteria are operational definitions: they specify clinical and laboratory findings used to classify a participant's status. The description gives CR, CRi, and PR criteria for AML and ALL. Defining these categories can improve consistency, because assessments are judged against stated rules rather than an informal impression. The record does not state how the categories were combined for overall response, whether the same definitions applied to all listed malignancies, or how disagreements between assessors would be resolved. Those details are not reported in the registry record.

Why does the endpoint schedule matter?

Response can change over time, so assessment timing affects what an endpoint represents. The registry lists assessment at 8 weeks after infusion, then 6 months after and every 4 months for approximately 2 years. An outcome at an early assessment answers a different descriptive question from whether response is maintained across follow-up. A single summary can also depend on whether the analysis uses the first response, best response, response at a fixed visit, or another rule. The registry record does not describe that rule or report analyzed results at the scheduled assessments.

Incomplete follow-up can affect the interpretation of longitudinal assessments. If participants with missing visits differ from those with observed visits, a complete-case summary may not represent the enrolled group. General methods for missing data include reporting the amount and reasons for missingness, defining the analysis population, and conducting sensitivity analyses when appropriate. The record does not report missing-data methods, the completion of follow-up, or the handling of participants without an assessment.

How should precision and significance be understood?

An estimate describes the observed outcome; a confidence interval describes uncertainty around that estimate under specified assumptions. For a binary response endpoint, the interval would convey uncertainty about the response proportion, not just variation in the raw count. No primary estimate or confidence interval is reported in the registry record. A p-value tests a specified statistical hypothesis under a particular model and assumptions, but it does not measure the size or clinical importance of an effect. No primary analysis or p-value is reported.

With limited information about the number assessed and the observed response outcome, precision cannot be evaluated. A small enrolled group can make descriptive estimates sensitive to the outcome of individual participants, but the registry record does not report enough primary endpoint data to quantify that sensitivity. General statistical practice would present the count and denominator alongside an interval, explain the analysis population, and avoid treating a non-significant result as proof of no effect. This record offers no primary test result from which to make such an interpretation.

What do the planning assumptions mean?

Planning calculations are not observed trial outcomes. The stated illustration uses 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. Those are assumptions for hypothetical planning, not the design actually registered for this single-group study. Any sample-size figures associated with those assumptions should be read as participants per arm for a hypothetical comparison, not as a target or achieved property of this trial.

In general, a planning calculation asks how much information a future study might need to detect an effect under chosen assumptions. Its result depends on the assumed effect, variability, analysis method, and error rates. If an assumed effect comes from a small or unstable observed estimate, planning figures can also be uncertain. They do not establish the probability that this completed study detected an effect, and they are never observed power. The registry record does not report the trial's own sample-size justification or statistical plan.

Over-dispersion is a general issue when count outcomes vary more than a statistical model expects. It can make model-based standard errors too small if not accounted for. The primary endpoint is described as a participant count, but no count analysis or model is reported; over-dispersion should therefore not be presumed to have been assessed. For a binary response, the main issues would include the denominator, the response definition, and uncertainty around the proportion. The registry record does not report those analyzed quantities.

What can safety summaries establish?

Adverse event summaries describe events recorded during a study and the participants associated with them. Seriousness is a regulatory classification, not a judgment that the event was caused by treatment. A term appearing in a serious adverse event list should therefore be read as a reported event category, not evidence of causal attribution. A percentage alone does not communicate event timing, duration, severity, recurrence, or the participant-level overlap among terms. Those details are not reported in the registry record.

Comparative safety inference usually requires consistent observation and an appropriate comparison. This study has no concurrent comparator group, and the registry record does not report a comparative safety analysis. The listed entries can describe what the registry records for the Cellular Immunotherapy group, but they cannot isolate risk attributable to the infusion from the background risk of the diseases or other care.

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("Cellular Immunotherapy")
n      <- c(5)
events <- c(1)
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  Cellular Immunotherapy  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record reports two outcome measures: the primary overall response endpoint and a secondary outcome concerning the rate of dose-limiting toxicities of HLA haploidentical peripheral blood phereseed cellular infusions. It reports zero analyses. A multiplicity strategy for handling several endpoints or repeated assessments is not reported in the registry record. Without such a strategy or posted tests, the effect of multiple statistical questions on interpretation cannot be evaluated.

Missing-data handling is also not reported in the registry record. The primary outcome schedule includes assessments at 8 weeks after infusion, then 6 months after and every 4 months for approximately 2 years, but the record does not report how many assessments were completed, why any were missing, or how missing outcomes were treated. It does not state whether participants without an assessment were excluded, counted as nonresponders, or handled through another method. No such method should be assumed.

The primary outcome population field is blank. The registry does not specify the analysis population, such as whether all enrolled participants or only those with an evaluable response assessment were included. The enrollment is listed as 6, but enrollment is not a substitute for an endpoint denominator. The record does not report participant flow from enrollment through treatment, follow-up, and analysis, or whether any participants withdrew or were excluded.

These omissions matter because endpoint definitions, analysis populations, and missing-data rules can change an estimate. They also limit reproducibility: readers cannot reconstruct an analysis without a stated denominator and method. The posted record supports identifying the planned outcomes, but not judging whether multiplicity or missingness influenced a primary result.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dizziness (66.7%), hypotension (50.0%), anemia (33.3%), fever (33.3%), albumin (16.7%).

For the Cellular Immunotherapy group, the registry fields list 6 at risk and 6 affected for both serious and other adverse events. The serious adverse event terms listed are dizziness at 66.7%, hypotension at 50.0%, anemia and fever at 33.3%, and Albumin and ALT at 16.7%. These are registry-reported categories and percentages, not a comparison against another group.

The percentages should not be interpreted as evidence that cellular immunotherapy caused the events. A serious adverse event is classified by seriousness; causal relationship to treatment is a separate judgment. The registry record does not report the event-level attribution, timing, duration, severity grading, or whether the listed terms refer to overlapping participants. It also does not explain the denominator used for each listed percentage.

The record includes no concurrent control group, so it cannot show whether the listed events occurred more or less often than they would have under another treatment. The safety entries describe reported events in this study group, but they do not by themselves establish comparative risk or causation. The reason for termination and its relationship, if any, to safety are not reported in the registry record.

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

The record establishes that a phase 2, single-group study of cellular immunotherapy was registered for patients with relapsed or refractory hematological malignancies. It describes the donor cell infusion, the primary response endpoint, the response criteria for AML and ALL, a follow-up schedule, and several listed serious adverse event terms. These details clarify the intended clinical question and the types of outcomes the study planned to assess.

The record does not report primary response results. There is no response count, response rate, confidence interval, or analysis in the posted results. Therefore, the record does not show the observed magnitude of response or how precisely it was estimated. Enrollment alone cannot fill that gap, and the listed safety percentages are not substitutes for primary endpoint results.

Even with a posted response estimate, a single-group design would describe outcomes among treated participants rather than provide a randomized comparison with another approach. Such a description may be informative, but interpretation must account for the lack of a control group, the range of malignancies, the endpoint's stated criteria, and the completeness of follow-up. Condition-specific estimates, a detailed analysis population, and missing-data methods are not reported in the registry record.

The safety listings also have a limited interpretation. They identify terms and percentages recorded for the group, but do not establish attribution, comparative risk, or the clinical context of each event. The registry record does not report detailed safety analyses or a reason for study termination. Overall, the available information supports a description of study design and registry-listed safety categories, but not a conclusion about response magnitude, treatment effect, or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates why a registered clinical question and an analyzed result are not the same thing. The record describes a response endpoint and assessment schedule, but reports zero analyses and no primary response count or rate. Without the observed outcome and its denominator, readers cannot estimate response or assess its precision. A registry entry can therefore be useful for understanding what was intended while still leaving the central statistical question unanswered.

The design also matters. A single-group study can document what occurred among participants receiving an intervention, but has no concurrent control to distinguish intervention-associated outcomes from other explanations. This is especially important when the eligible conditions span several hematological malignancies. Overall summaries may combine clinically different groups, and condition-specific outcomes are not reported in the registry record.

Safety summaries make a related point: listed event terms can be described, but percentages do not establish causation or comparative risk. Interpretation depends on definitions, denominators, event-level context, and consistent follow-up. The record does not provide all of those details.

Finally, the study is marked terminated without a reported reason. That status is relevant context, but does not explain whether follow-up was complete or whether termination affected analysis. These limitations are not unique to this study; they show why transparent reporting of participant flow, outcome counts, analysis populations, missing data, and uncertainty is essential for evaluating clinical evidence.

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 primary limitation is that the registry record does not report an analysis of the primary response endpoint. No response count, denominator, response rate, or uncertainty interval is available. Although enrollment is listed as 6, the record does not show how many participants received the infusion, had an evaluable assessment, or contributed to an endpoint analysis.

The study includes a range of hematological malignancies, but the primary outcome population field is blank and condition-specific results are not reported. The response description gives detailed AML and ALL criteria, but does not explain how response was defined for each listed lymphoma or how categories were combined into overall response. The assessment schedule is stated, while the rule for using repeated assessments is not.

The single-group design has no concurrent comparator, so the record cannot support a randomized treatment-effect estimate. Masking is listed as none, and details of outcome assessment or independent review are not reported. The registry does not describe missing-data methods, analysis populations, multiplicity handling, or the statistical plan. These gaps make it difficult to evaluate bias, precision, and reproducibility.

The safety information is limited to group fields and listed serious adverse event terms with percentages. Event-level attribution, timing, severity, overlap, and the denominator for each percentage are not reported in the registry record. The study is marked terminated, but the reason is not reported. The record also does not explain whether termination affected planned assessments or follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma — NCT01685606.
• Registry record last updated 2022-03-04; status last verified 2022-02.
• Results first posted 2015-06-26.
• 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

NCT01685606 is a phase 2, single-group study sponsored by Brown University and marked terminated. It enrolled 6 participants and evaluated cellular immunotherapy using donor lymphocytes from a haploidentical donor. The listed conditions include mantle cell lymphoma, diffuse large cell lymphoma, Burkitts lymphoma, T cell lymphomas, and acute myeloid leukemia/acute lymphoblastic leukemia.

The primary outcome was overall response, recorded as a participant count, with assessment at 8 weeks after infusion, then 6 months after and every 4 months for approximately 2 years. A secondary outcome concerned dose-limiting toxicities. The registry reports two outcome measures and zero analyses; the primary response result and reason for termination are not reported in the registry record.

The registry lists serious adverse event terms and percentages for the Cellular Immunotherapy group, but no comparative safety analysis. The available record describes the study question and planned outcomes, while leaving response magnitude, precision, analysis population, and missing-data handling unreported.