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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Heidelberg University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Heidelberg University
ClinicalTrials.gov Identifier:
NCT00571168
First received: December 10, 2007
Last updated: January 11, 2010
Last verified: January 2010
  Purpose
  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 Intervention Phase
Multiple Myeloma
Drug: Emend
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Overall complete response (no emesis and no rescue therapy) [ Time Frame: During and post chemotherapy (0-120 h) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response acute/delayed phase [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • Vomiting event rate [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • No emesis (FLIE-Score) [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • No (significant) nausea (VAS < 5 mm;(< 25 mm)) [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • No rescue therapy [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • Total control (no emesis, no nausea, no rescue therapy) [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • No impact on daily life [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]
  • AEs [ Time Frame: During and post chemotherapy (0-120h) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 362
Study Start Date: July 2005
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571168

Contacts
Contact: Gerlinde Egerer, MD ++49(0)6221 56-8002 Gerlinde.Egerer@med.uni-heidelberg.de

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

No publications provided

Responsible Party: Gerlinde Egerer / MD, University of Heidelberg
ClinicalTrials.gov Identifier: NCT00571168     History of Changes
Other Study ID Numbers: EmNa (2001-004956-38), EudraCT-No: 2004-004956-38
Study First Received: December 10, 2007
Last Updated: January 11, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Aprepitant
Fosaprepitant
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014