A Phase I/II Study of the PD-1 Antibody Nivolumab in Combination with Lenalidomide in Relapsed/Refractory Non-Hodgkin Lymphoma and Hodgkin Disease
Hypothesis: The combination of nivolumab and lenalidomide will be safe, tolerable and effective in patients with B-cell non-Hodgkin lymphoma (NHL) or with Hodgkin disease (HD), regardless of their prognostic marker profile. Patient responses to the combination are expected to be better than responses to the agents when used alone.
Study Design: This phase I/II, open-label, single-institution study will determine the safety, tolerability and maximum tolerated dose or the recommended phase II dose of lenalidomide combined with nivolumab in patients with relapsed/refractory NHL, with an expansion cohort in HD and a phase II study in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and relapsed/refractory follicular lymphoma (FL). Along with assessing response, it will help determine whether a particular NHL histology results in greater benefit from the combined agents.
Rationale: This trial will help meet the need for therapies that are effective and have minimal toxicity in subsets of patients with NHL and HD.
NHL is often curable with frontline therapy, but 30-40 percent of DLBCL patients relapse. The only curative option is high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT). For patients who are not candidates for HDT/ASCT due to age or comorbidities, salvage regimens provide short responses and unacceptable toxicity.
FL is the most common indolent NHL. Some patients require no therapy for several years and achieve long remissions with treatment; others require immediate therapy, relapse quickly or are refractory to treatment and experience shortened survival. About 30 percent of FL patients transform to aggressive disease and require intensive therapy. FL is usually considered incurable, although outcomes have significantly improved with the use of rituximab and other monoclonal anti-CD20 antibodies.
HD shows five-year progression-free survival (PFS) rates of 61-89 percent after front-line therapy, but patients with poor prognostic factors relapse or have refractory disease. As in NHL, relapsed patients are treated with HDT/ASCT, and about 50 percent have prolonged PFS.
Lenalidomide is an immune modulator that shows clinical activity in both aggressive and indolent relapsed/refractory NHL and in relapsed/refractory HD. It is well tolerated with minimal toxicity, primarily myelosuppression and rash.
Nivolumab is a PD-1 inhibitor that is approved in relapsed/ refractory HD and has shown early signs of efficacy in other hematologic malignancies. The most frequent adverse events include fatigue, rash, diarrhea, decreased appetite, nausea and pruritis.
Preclinical evidence suggests that nivolumab in combination with lenalidomide might improve response rates, depth of remission, and duration of responses in patients with relapsed/refractory NHL and HD.
At a Glance
Trial no.: ClinicalTrial OSU-16167
gov identifier: NCT03015896
Phone: 614-293-3196
Email: Kami.Maddocks@osumc.edu
Eligibility: Histologically confirmed B-cell NHL (DLBCL, FL, MCL, MZL, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia); Burkitt lymphoma transformed to DLBCL; confirmed classical or lymphocyte predominant HD that is relapsed or refractory after at least one prior chemotherapy; has had at least one prior therapy, including prior ASCT; 18 years of age or older, and must be willing and able to provide written informed consent/assent.