First Interim Safety Analysis of a Phase III Randomized Trial in Newly Diagnosed Systemic Peripheral T-Cell Lymphoma Treated with CHOP Chemotherapy with or without Alemtuzumab and Consolidated by Autologous Hematopoietic Stem Cell Transplant

• Published in: Blood 2011-11, Vol.118 (21), p.4110-4110
• Main Authors: d'Amore, Francesco, da Silva, Maria Gomes, Leppa, Sirpa, Relander, Thomas, Pezzutto, Antonio, Lauritzsen, Grete F., Weidmann, Eckhart, Van Gelder, Michel, Merup, Mats, Hagberg, Hans, Fagerli, Unn-Merete, Brown, Peter de Nully, Hansen, Per Boye, Mariz, Jose Mario, Jankovska, Milada, Walewski, Jan, Doorduijn, Jeanette, Van Hoof, Achiel, Christiansen, Ilse, Jyrkkiö, Sirkku, Kluin-Nelemans, J.C., van Marwijk Kooy, Marinus, Fijnheer, Rob, Stevens, Wendy, Zijlstra, Josee, Böhmer, L., Lugtenburg, P.J., Grube, Matthias, Prochazka, Vit, Salek, David, Greil, Richard, Trümper, Lorenz, Wulf, Gerald, Altmann, Bettina, Ziepert, Marita, Loeffler, Markus, Jantunen, Esa, Hopfinger, Georg, Neste, Eric Van den, Toldbod, Helle
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.4110.4110

Abstract 4110 The ACT trial (ACT-1 and −2) tests the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP (A-CHOP-14) followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT/ASCT) in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). To date, the trial has accrued a total of 131 patients (ACT-1 n=72; ACT-2 n=59). Here, we present the first planned interim safety analysis of the ACT-1 trial based on the first 51 randomized patients. The aim of the present analysis is to report on the feasibility of a dose-dense chemo-immunotherapy schedule combining ALZ and bi-weekly CHOP followed by HDT/ASCT in ‘de novo’ PTCL patients. Results contain two data subsets corresponding to ALZ dose levels prior and subsequent to a dose-reduction amendment tapering ALZ dose from 360 mg (30 mg on days 1 and 2 of each CHOP course) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively. Of the 51 randomized patients, 43 had a complete set of evaluable data and represent the background for the present set of results. Of these, 5 received the higher ALZ dose, 17 the lower and 21 belonged to the antibody-void control arm. Treatment arms were well balanced with regard to histological subtypes, IPI sub-groups, and single prognostic factors. Neither of the two treatment cohorts, and for the experimental one irrespective of ALZ dose level, showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 3–4 leucopenia and anemia were more frequent in ALZ-treated patients (71% vs 29% and 47% vs 14%, respectively), whereas no difference was seen in terms of thrombocytopenia (17% vs 18%). Non-hematological toxicity unrelated to infectious complications was similar in the two groups. At the higher ALZ dose level, two cases of systemic fungal infection were reported, of which one (verified as being aspergillosis) with fatal outcome in a patient with pre-existing type II diabetes and steroid-requiring chronic obstructive pulmonary disease. These two events prompted the ALZ dose-reduction amendment, which led to a significant drop in the number of serious adverse events (SAEs) for ALZ-treated patients (SAE/patient pre-amendment: 2.6, post-amendment: 0.76) to a level comparable with th