1. 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).
- Author
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Gillessen S, Hüttmann A, Vucinic V, Müller H, Plütschow A, Viardot A, Topp MS, Kobe C, Böll B, Eichenauer DA, Sasse S, Haverkamp H, Schmitz C, Borchmann S, Bröckelmann PJ, Heger JM, Fuchs M, Engert A, Borchmann P, and von Tresckow B
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Cytarabine administration & dosage, Dexamethasone administration & dosage, Drug Resistance, Neoplasm, Everolimus administration & dosage, Female, Germany, Hodgkin Disease diagnosis, Hodgkin Disease etiology, Hodgkin Disease mortality, Humans, Induction Chemotherapy, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Positron-Emission Tomography, Prognosis, Recurrence, Remission Induction, Retreatment, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- 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., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
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