A Pilot Trial of Campath-1H and Dose-Adjusted EPOCH in CD52-Expressing Aggressive T-Cell Malignancies.
Authors: Janik John E. , Dunleavy Kieron , Pittaluga Stefania , Jaffe Elaine S. , Grant Nicole , Shovlin Margaret , Stetler-Stevenson Maryalice , Wilson Wyndham H. 
Published: April 2020

Abstract
Patients with aggressive T-cell non-Hodgkin’s lymphoma (NHL) treated with chemotherapy have a prognosis that is significantly inferior to that of B-cell NHL. Chemotherapy combined with CD20 monoclonal antibody therapy further improves the outcome for patients with B-cell NHL. The paradigm of combining monoclonal antibodies and chemotherapy has improved outcome for a variety of malignancies. Monoclonal antibodies directed against T cell antigens are available and it is important to evaluate their efficacy in combination with chemotherapy for the treatment of T-cell malignancies. We are conducting a single-center phase I dose escalation trial of Campath-1H with dose-adjusted EPOCH (DA-EPOCH) infusional chemotherapy to assess the maximum tolerated dose (MTD) and safety in patients (pts) with CD52-positive aggressive NHL. A single infusion of Campath-1H (30, 60, or 90 mg) is given over 12 hours before each cycle of chemotherapy; pts are premedicated with Prednisone 12 hrs before the Campath infusion is initiated. DA-EPOCH was initiated immediately following completion of the Campath infusion. Toxicity during the first cycle of treatment was used to determine Campath dose escalation. Pts were required to be chemotherapy naive and to express CD52 on the malignant T-cells. 17 pts were evaluated for eligibility and 14 pts treated; 3 were ineligible due to absence of expression of CD52 as assessed by flow cytometry on the malignant T-cells (2 with NK-T cell nasal lymphoma and 1 with CD30 positive peripheral T-cell lymphoma). 14 pts were entered (6 Peripheral T-cell lymphoma (NOS), 4 Adult T-cell leukemia/lymphoma, 2 Angioimmunoblastic T-cell lymphoma, 2 hepatosplenic T-cell lymphoma); 8 pts were treated at dose level 1 (30 mg), 3 at dose level 2 (60 mg), and 3 at dose level 3 (90 mg). The median age of treated pts was 35 years (range 17–77), median IPI 3 (range 0–5). A total of 56 cycles of treatment were administered. 2 of the 14 pts treated experienced grade 3 hypersensitivity reactions; most pts experienced grade 1–2 allergic and infusional reactions manifested as fever, chills, and urticaria. Although not originally incorporated into the definition of dose-limiting toxicity, bone marrow suppression with reversible bone marrow aplasia prevented the administration of further treatment in 2 pts at the 60 mg dose level (cycle 3 and 5) and 2 pts at the 90 mg dose level (cycle 4 and 5) of Campath. 3 of these 4 pts were CMV antigen positive and were treated with oral or intravenous gangciclovir. Grade 4 neutropenia was observed in all pts (12 during cycle 1) and grade 4 thrombocytopenia in 4 pts (3 in cycle 1). All but one pt developed grade 4 lymphopenia. Documented infections were observed in 11 pts and included bacterial, fungal and viral pathogens. 5 pts were CMV antigen positive during treatment; 2 pts developed hemorrhagic cystitis associated with BK virus infection that resolved despite continued treatment. Half of the pts entered have died due to progressive lymphoma, 5 are in complete remission (17, 10, 9, 7, 3 months) and two are too early to evaluate. Accrual at the 30 mg dose level of Campath is ongoing. Bone marrow suppression that prevented completion of therapy has not been observed in any patient treated at the 30 mg dose of Campath and appears safe for combination with DA-EPOCH for phase II evaluation.