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

Randomised, Placebo Controlled, Single-center, Double-blind Clinical Trial to Investigate Efficacy and Safety of Aprepitant Combined With Kevatril and Dexamethasone Versus Placebo Combined With Kevatril and Dexamethasone in Prevention of Acute and Delayed High-dose Chemotherapy-induced Nausea and Vomiting in Subjects With Multiple Myeloma Receiving an Autologous Peripheral Blood Stemcell Transplantation.

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Emend; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 362
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gerlinde Egerer, MD; Phone Number: ++49(0)6221 56-8002; Email: Gerlinde.Egerer@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University Hospital of Heidelberg, Department V
    • Principal Investigator: Gerlinde Egerer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Aprepitant plus standard therapy (Kevatril + Dexamethason) on day 1-4	Drug: Emend; 125 mg/d on day 1; 80 mg/d on day 2-4
Placebo Comparator: B; Placebo plus standard therapy (Kevatril + Dexamethason) on day 1-4	Drug: Placebo; Placebo capsules on day 1-4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall complete response (no emesis and no rescue therapy)	During and post chemotherapy (0-120 h)

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete response acute/delayed phase	During and post chemotherapy (0-120h)
Vomiting event rate	During and post chemotherapy (0-120h)
No emesis (FLIE-Score)	During and post chemotherapy (0-120h)
No (significant) nausea (VAS < 5 mm;(< 25 mm))	During and post chemotherapy (0-120h)
No rescue therapy	During and post chemotherapy (0-120h)
Total control (no emesis, no nausea, no rescue therapy)	During and post chemotherapy (0-120h)
No impact on daily life	During and post chemotherapy (0-120h)
AEs	During and post chemotherapy (0-120h)

Collaborators and Investigators

• Sponsor: Heidelberg University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Gerlinde Egerer, MD, University Hospital of Heidelberg; Im Neuenheimer Feld 410; 69120 Heidelberg/ Germany

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: December 10, 2007
• First Submitted That Met QC Criteria: December 10, 2007
• First Posted (Estimate): December 11, 2007

Study Record Updates

• Last Update Posted (Estimate): January 12, 2010
• Last Update Submitted That Met QC Criteria: January 11, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: chemotherapy induced nausea and vomiting; high dose chemotherapy; autologous peripheral blood stemcell transplantation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: EmNa (2001-004956-38); EudraCT-No: 2004-004956-38