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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00571168
Recruitment Status : Unknown
Verified January 2010 by Heidelberg University.
Recruitment status was:  Recruiting
First Posted : December 11, 2007
Last Update Posted : January 12, 2010
Merck Sharp & Dohme Corp.
Information provided by:
Heidelberg University

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Emend Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 362 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : July 2005
Estimated Primary Completion Date : December 2010
Estimated Study Completion Date : December 2010

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

Primary Outcome Measures :
  1. Overall complete response (no emesis and no rescue therapy) [ Time Frame: During and post chemotherapy (0-120 h) ]

Secondary Outcome Measures :
  1. Complete response acute/delayed phase [ Time Frame: During and post chemotherapy (0-120h) ]
  2. Vomiting event rate [ Time Frame: During and post chemotherapy (0-120h) ]
  3. No emesis (FLIE-Score) [ Time Frame: During and post chemotherapy (0-120h) ]
  4. No (significant) nausea (VAS < 5 mm;(< 25 mm)) [ Time Frame: During and post chemotherapy (0-120h) ]
  5. No rescue therapy [ Time Frame: During and post chemotherapy (0-120h) ]
  6. Total control (no emesis, no nausea, no rescue therapy) [ Time Frame: During and post chemotherapy (0-120h) ]
  7. No impact on daily life [ Time Frame: During and post chemotherapy (0-120h) ]
  8. AEs [ Time Frame: During and post chemotherapy (0-120h) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00571168

Contact: Gerlinde Egerer, MD ++49(0)6221 56-8002

University Hospital of Heidelberg, Department V Recruiting
Heidelberg, Germany, 69120
Principal Investigator: Gerlinde Egerer, MD         
Sponsors and Collaborators
Heidelberg University
Merck Sharp & Dohme Corp.
Principal Investigator: Gerlinde Egerer, MD University Hospital of Heidelberg; Im Neuenheimer Feld 410; 69120 Heidelberg/ Germany

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Gerlinde Egerer / MD, University of Heidelberg Identifier: NCT00571168     History of Changes
Other Study ID Numbers: EmNa (2001-004956-38)
EudraCT-No: 2004-004956-38
First Posted: December 11, 2007    Key Record Dates
Last Update Posted: January 12, 2010
Last Verified: January 2010

Keywords provided by Heidelberg University:
chemotherapy induced nausea and vomiting
autologous peripheral blood stemcell transplantation
high dose chemotherapy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action