Reinduction therapy with everolimus in combination with dexamethasone, high-dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD-R3i).
|
| Abstract |
Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18-60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0-13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.
|
|---|---|
| Authors | Sarah Gillessen, Andreas Hüttmann, Vladan Vucinic, Horst Müller, Annette Plütschow, Andreas Viardot, Max S Topp, Carsten Kobe, Boris Böll, Dennis A Eichenauer, Stephanie Sasse, Heinz Haverkamp, Christine Schmitz, Sven Borchmann, Paul J Bröckelmann, Jan-Michel Heger, Michael Fuchs, Andreas Engert, Peter Borchmann, Bastian von Tresckow |
| Journal | British journal of haematology (Br J Haematol) Vol. 196 Issue 3 Pg. 606-616 (02 2022) ISSN: 1365-2141 [Electronic] England |
| PMID | 34775591 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't) |
| Copyright | © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!