Trial · NCT03038672
Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
NCT03038672, Phase 2, Active not recruiting, National Cancer Institute (NCI); results first posted 2024-10-16
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas. Trials, record NCT03038672. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03038672
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
- NCT number
- NCT03038672
- Status
- Active not recruiting
- Phases
- Phase 2
- Enrollment
- 54 participants, actual
- Lead sponsor
- National Cancer Institute (NCI)
- Conditions
ALK-Positive Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma Activated B-Cell Type, Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation, Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, EBV-Positive Mucocutaneous Ulcer, HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Intravascular Large B-Cell Lymphoma, Large B-Cell Lymphoma With 11q Aberration, Large B-Cell Lymphoma With IRF4 Rearrangement, Plasmablastic Lymphoma, Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System, Primary Effusion Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Burkitt Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Gray-Zone Lymphoma, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent Lymphomatoid Granulomatosis, Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Recurrent Primary Mediastinal Large B-Cell Lymphoma, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Burkitt Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Gray-Zone Lymphoma, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Refractory Primary Mediastinal Large B-Cell Lymphoma, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
- Interventions
- Nivolumab, Varlilumab
- First posted
- 2017-02-01
- Last updated
- 2026-10-26
- Results first posted
- 2024-10-16
Source ClinicalTrials.gov
Registered outcomes11
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Overall Response Rate | 2 years | Will be assessed by computed tomography (CT)-based criteria or positron emission tomography (PET)-CT based criteria. A response will be defined as an objective status of partial remission (PR) or complete remission (CR) for patients evaluated by CT-based criteria and complete metabolic response (CMR) or partial metabolic response (PMR) for patients evaluated by PET-CT based criteria. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm. Comparison of overall response rates between the two treatment groups will be performed using a one-sided Fisher's exact test at significance level 0.15. |
| Secondary | Duration of Response | 2 years | Defined as the date at which the patient's objective status is first noted to be a PR or CR for patients evaluated by CT-based criteria or CMR or PMR for patients evaluated by PET-CT based criteria to the earliest date progression (documentation of disease progression \[PMD\] or progressive disease \[PD\]) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. The comparison of duration of response between two treatment arms will be based on the log-rank test. |
| Secondary | Overall Survival | 37 months | The distribution of survival time will be estimated using the method of Kaplan-Meier. The comparison of overall survival between two treatment arms will be based on the log-rank test. |
| Secondary | Progression Free Survival (PFS) | 37 months | The distribution of PFS will be estimated using the method of Kaplan-Meier. The comparison of progression-free survival between two treatment arms will be based on the log-rank test. |
| Secondary | Proportion of Patients With Grade 3 or Higher Adverse Events | 25 months | Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The overall adverse event rates for grade 3 or higher hematologic and non-hematologic adverse events at least possibly related to treatment will be compared between the two treatment groups using the Chi-square test (or Fisher's exact test if the data in the contingency table is sparse). |
| Other | Change in CD27 Expression in Tissue | Baseline up to 100 days after last dose of study drug | Will be assessed by immunohistochemistry. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, overall survival \[OS\]) will be evaluated using Cox's proportional hazards models and log-rank tests. Logistic regression will be used to model the response rate as a function of treatment and CD27 (as a continuous variable). The distribution of CD27 will be estimated empirically in the entire trial population and used to calculate CD27 values corresponding to each fixed percentile. |
| Other | Change in Peripheral Blood Immune Cells | Baseline up to 12 weeks | Will be assessed by cytometry by time of flight (CyTOF). The relationship between presence/absence of a particular subtype of cell and association with outcomes will be evaluated. Evaluation of particular combinations of immune cells (immune signature) and whether they are predictive of outcome will also be evaluated. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests. |
| Other | Change in the Identification/Characterization of Intratumoral Immune Cells in Tissue | Baseline up to time of disease progression | Will be assessed by immunohistochemistry and CyTOF. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests. |
| Other | Change in Genetic Alterations of Chromosome 9p24.1 in Tissue | Baseline up to time of disease progression | Will be assessed by fluorescence in situ hybridization. The proportion of patients in each of these groups who achieve a response will be evaluated. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests. |
| Other | Change in Serum Cytokine Profile | Baseline up to 12 weeks | Will be assessed by enzyme-linked immunosorbent assay. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests. |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 registered outcomesOutcomes11
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Overall Response Rate | 2 years | All eligible patients that had a disease evaluation after being treated. | proportion of participants | NUMBER |
| SECONDARY | Duration of Response | 2 years | All eligible and treated patients that achieve a response. | years | MEDIAN |
| SECONDARY | Overall Survival | 37 months | All eligible and treated patients. | Months | MEDIAN |
| SECONDARY | Progression Free Survival (PFS) | 37 months | All eligible and treated patients that had a disease evaluation. | Months | MEAN |
| SECONDARY | Proportion of Patients With Grade 3 or Higher Adverse Events | 25 months | All eligible and treated patients. | proportion of patients | NUMBER |
| OTHER_PRE_SPECIFIED | Change in CD27 Expression in Tissue | Baseline up to 100 days after last dose of study drug | |||
| OTHER_PRE_SPECIFIED | Change in Peripheral Blood Immune Cells | Baseline up to 12 weeks | |||
| OTHER_PRE_SPECIFIED | Change in the Identification/Characterization of Intratumoral Immune Cells in Tissue | Baseline up to time of disease progression | |||
| OTHER_PRE_SPECIFIED | Change in Genetic Alterations of Chromosome 9p24.1 in Tissue | Baseline up to time of disease progression | |||
| OTHER_PRE_SPECIFIED | Change in Serum Cytokine Profile | Baseline up to 12 weeks |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 outcomesResults by group10
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Overall Response Rate | Group I (Nivolumab) | 0.16 | 95% Confidence Interval 0.045 to 0.361 | proportion of participants | |
| Overall Response Rate | Group II (Varlilumab, Nivolumab) | 0.08 | 95% Confidence Interval 0.010 to 0.251 | proportion of participants | |
| Duration of Response | Group I (Nivolumab) | NA | 95% Confidence Interval NA to NA | years | |
| Duration of Response | Group II (Varlilumab, Nivolumab) | 0.2 | 95% Confidence Interval 0.2 to NA | years | |
| Overall Survival | Group I (Nivolumab) | 8.6 | 95% Confidence Interval 4.7 to NA | Months | |
| Overall Survival | Group II (Varlilumab, Nivolumab) | 10.2 | 95% Confidence Interval 3.1 to NA | Months | |
| Progression Free Survival (PFS) | Group I (Nivolumab) | 2.6 | 95% Confidence Interval 1.5 to 3.2 | Months | |
| Progression Free Survival (PFS) | Group II (Varlilumab, Nivolumab) | 1.5 | 95% Confidence Interval 1.1 to 3.2 | Months | |
| Proportion of Patients With Grade 3 or Higher Adverse Events | Group I (Nivolumab) | 0.76 | proportion of patients | ||
| Proportion of Patients With Grade 3 or Higher Adverse Events | Group II (Varlilumab, Nivolumab) | 0.84 | proportion of patients |
Source ClinicalTrials.gov
Participant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Initial Treatment | STARTED | Group I (Nivolumab) | 27 | |
| Initial Treatment | STARTED | Group II (Varlilumab, Nivolumab) | 27 | |
| Initial Treatment | COMPLETED | Group I (Nivolumab) | 25 | |
| Initial Treatment | COMPLETED | Group II (Varlilumab, Nivolumab) | 26 | |
| Initial Treatment | NOT COMPLETED | Group I (Nivolumab) | 2 | |
| Initial Treatment | NOT COMPLETED | Group II (Varlilumab, Nivolumab) | 1 | |
| Cross Over From Group I to Group II | STARTED | Group I (Nivolumab) | 7 | |
| Cross Over From Group I to Group II | STARTED | Group II (Varlilumab, Nivolumab) | 26 | |
| Cross Over From Group I to Group II | COMPLETED | Group I (Nivolumab) | 7 | |
| Cross Over From Group I to Group II | COMPLETED | Group II (Varlilumab, Nivolumab) | 26 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events555
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anemia | Blood and lymphatic system disorders | Group I (Nivolumab) | 8 | 27 | 8 |
| other | Anemia | Blood and lymphatic system disorders | Group II (Varlilumab, Nivolumab) | 13 | 27 | 18 |
| other | Anemia | Blood and lymphatic system disorders | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 1 | 7 | 1 |
| other | Blood and lymph sys disorders - Oth Spec | Blood and lymphatic system disorders | Group I (Nivolumab) | 3 | 27 | 3 |
| other | Blood and lymph sys disorders - Oth Spec | Blood and lymphatic system disorders | Group II (Varlilumab, Nivolumab) | 5 | 27 | 5 |
| other | Blood and lymph sys disorders - Oth Spec | Blood and lymphatic system disorders | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 1 | 7 | 1 |
| other | Leukocytosis | Blood and lymphatic system disorders | Group I (Nivolumab) | 0 | 27 | 0 |
| other | Leukocytosis | Blood and lymphatic system disorders | Group II (Varlilumab, Nivolumab) | 2 | 27 | 2 |
| other | Leukocytosis | Blood and lymphatic system disorders | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 0 | 7 | 0 |
| other | Atrioventricular block complete | Cardiac disorders | Group I (Nivolumab) | 1 | 27 | 1 |
1 to 10 of 555Source ClinicalTrials.gov
See all 555 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Group I (Nivolumab) | 3 | 27 |
| Total, all-cause mortality | Group II (Varlilumab, Nivolumab) | 5 | 27 |
| Total, all-cause mortality | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 0 | 7 |
| Total, other adverse events | Group I (Nivolumab) | 24 | 27 |
| Total, other adverse events | Group II (Varlilumab, Nivolumab) | 24 | 27 |
| Total, other adverse events | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 7 | 7 |
| Total, serious adverse events | Group I (Nivolumab) | 10 | 27 |
| Total, serious adverse events | Group II (Varlilumab, Nivolumab) | 12 | 27 |
| Total, serious adverse events | Cross Over to Group II Treatment (Varlilumab, Nivolumab) | 3 | 7 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants2
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years | Source |
|---|---|---|---|---|---|---|
| UM1CA186709 | Dana-Farber/Harvard Cancer Center Experimental Therapeutics Clinical Trials Network Site (DF/HCC ETCTN Site) | SHAPIRO, GEOFFREY I.; FLAHERTY, KEITH T; KUFE, DONALD W. | DANA-FARBER CANCER INST | NATIONAL CANCER INSTITUTE | 2014 to 2025 | NIH RePORTER |
| UM1CA186686 | NCI Experimental Therapeutics-Clinical Trials Network with Phase 1 Emphasis | ADJEI, ALEX A. | MAYO CLINIC ROCHESTER | NATIONAL CANCER INSTITUTE | 2014 to 2019 | NIH RePORTER |
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03038672
GET https://conductscience.org/api/trials/v1/NCT03038672/events?page=2