Efficacy and Safety of Aprepitant in Subjects With Multiple Myeloma During and After High-dose Chemotherapy
Status:
Unknown status
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
1. Scientific background In patients with multiple myeloma high-dose chemotherapy followed
by autologous stemcell transplantation is preferred to conventional therapy, since the
superiority in respect to complete remission, complete remission duration, event-free
survival and overall survival has been proven within well controlled clinical trials
(Fassas et al., 2002; Goldschmidt et al., 2003).
Nausea and vomiting are well known and the most distressing side-effects of a high dose
chemotherapy regimen. The administration of selective 5-HT3-receptor antagonists (5-HT3
RAs) in combination with a corticosteroid (= antiemetic standard therapy) is effective
for the prevention of those adverse effects in 70 to 80 % of patients. However, 25 to 40
% of the patients still suffer from vomiting and nausea in the delayed phase of the
chemotherapy. Superior protection could be achieved with the addition of Aprepitant
(EMEND®) to the antiemetic standard therapy in acute and delayed phases of highly
emetogenic chemotherapies. The enhanced antiemetic protection can be maintained over
multiple chemotherapy-cycles to an extent superior to that of standard therapy alone (de
Wit et al., 2003).
Furthermore addition of Aprepitant (EMEND®) to standard therapy was generally well
tolerated and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily
life was significantly reduced (Hesketh et al., 2003; Dando & Perry, 2004).
2. Trial Rationale Aprepitant (EMEND®) is a selective high-affinity receptor antagonist of
human substance P/neurokinin-1 (NK1) and has been shown to inhibit emesis induced by
cytotoxic chemotherapeutic agents and augments the antiemetic activity of 5-HT3 RAs
(e.g. Granisetron, Ondansetron) and corticosteroids (e.g. Dexamethasone). Thus
Aprepitant (EMEND®) in addition to antiemetic standard therapy has been shown to possess
powerful superior protection and has been reported in several clinical trials to
significantly improve both acute and delayed CINV.
The aim of this study is to evaluate, during and up to 7 days after high-dose chemotherapy
with Melphalan (moderate emetogenic drug) followed by autologous peripheral blood stemcell
transplantation, an antiemetic treatment regimen in respect to efficacy and safety in
patients with multiple myeloma. To the best of our knowledge effects of Aprepitant on
Melphalan induced CINV have never been investigated.