Efficacy and Safety of Aprepitant in Subjects With Multiple Myeloma During and After High-dose Chemotherapy

NCT ID: NCT00571168

Last Updated: 2010-01-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 362 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2010-12-31

Brief 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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A

Aprepitant plus standard therapy (Kevatril + Dexamethason) on day 1-4

Group Type: EXPERIMENTAL

Emend

Intervention Type: DRUG

125 mg/d on day 1; 80 mg/d on day 2-4

B

Placebo plus standard therapy (Kevatril + Dexamethason) on day 1-4

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules on day 1-4

Interventions

Emend

125 mg/d on day 1; 80 mg/d on day 2-4

Intervention Type: DRUG

Placebo

Placebo capsules on day 1-4

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Men and women >/= 18 years
• Patients with multiple myeloma receiving high-dose chemotherapy (Melphalan) and autologous peripheral stemcell transplantation
• Signed informed consent

Exclusion Criteria

• Patients suffering from nausea and vomiting during the last 12 hours prior to planned high-dose chemotherapy
• Patients receiving antiemetics 24 hours prior to planned high-dose chemotherapy
• Intake of steroids
• History of hypersensitivity to the investigational product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
• Simultaneous intake of pimozide, terfenadine, astemizole
• Pregnant or nursing woman
• Mental condition rendering the subject incapable to understand the nature, scope and possible consequences of the trial
• Expected non-compliance in completing the subject´s diary and FLIE-score

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

University of Heidelberg

Principal Investigators

Gerlinde Egerer, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Heidelberg; Im Neuenheimer Feld 410; 69120 Heidelberg/ Germany

Locations

University Hospital of Heidelberg, Department V

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Gerlinde Egerer, MD

Role: CONTACT

Gerlinde.Egerer@med.uni-heidelberg.de

++49(0)6221 56-8002

References

Schmitt T, Goldschmidt H, Neben K, Freiberger A, Husing J, Gronkowski M, Thalheimer M, Pelzl le H, Mikus G, Burhenne J, Ho AD, Egerer G. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol. 2014 Oct 20;32(30):3413-20. doi: 10.1200/JCO.2013.55.0095. Epub 2014 Sep 15.

Reference Type: DERIVED

PMID: 25225424 (View on PubMed)

Other Identifiers

EudraCT-No: 2004-004956-38

Identifier Type: -

Identifier Source: secondary_id

EmNa (2001-004956-38)

Identifier Type: -

Identifier Source: org_study_id