Clinical Trial: Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomized Phase 2 Study of Varlilumab (CDX-1127) in Combination With Nivolumab in Patients With Relapsed or Refractory Aggressive B-Cell Lymphomas

Brief Summary: This randomized phase II trial studies how well nivolumab with or without varlilumab works in treating patients with aggressive B-cell lymphomas that have come back or do not respond to treatment. Monoclonal antibodies, such as varlilumab and nivolumab, may work by stimulating the immune system to attack cancer tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the anti-malignant cell activity of combination therapy with varlilumab and nivolumab as compared to nivolumab alone in patients with advanced aggressive B-cell non-Hodgkin lymphomas (NHL) based on the revised Lugano classification response criteria.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability profile of treatment with a combination of varlilumab and nivolumab in patients with advanced aggressive B-cell NHL.

II. To evaluate the duration of response, progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To determine the effect of combination therapy with varlilumab and nivolumab on the immune system as assessed by immunohistochemistry (IHC), mass cytometry (CyTOF) and changes in serum cytokine profile.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive nivolumab intravenously (IV) over 60 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.

GROUP II: Patients receive varlilumab IV over 90 minutes every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 60 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.

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.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of response [ Time Frame: Up to 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.
  • Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 100 days after last dose of study drug ]
    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).
  • Progression free survival (PFS) [ Time Frame: From registration to the earliest date of documentation of disease progression (PMD or PD) or death due to any cause, assessed for up to 2 years ]
    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.
  • Survival time [ Time Frame: From registration to death due to any cause, assessed for up to 2 years ]
    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.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 31, 2017
Date Started: December 8, 2017
Date Completion: November 30, 2019
Last Updated: April 23, 2017
Last Verified: April 2017