Aprepitant- and Olanzapine- Containing Anti-emetic Regimens With High Dose Melphalan

NCT02939287 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 14102001
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to help answer the following research question:

• Whether administration of an aprepitant containing regimen, an olanzapine containing regimen or regimen containing both will prevent nausea and vomiting better for patients undergoing an autologous stem cell transplant with melphalan chemotherapy. Both of these medications are approved by the United States Food and Drug Administration (FDA) for nausea and vomiting.
• Participants will be randomly assigned to one of the 3 treatment groups:
• Arm A: aprepitant containing anti-emetic therapy
• Arm B: olanzapine containing anti-emetic therapy
• Arm C: Aprepitant plus olanzapine containing anti-emetic therapy

Conditions

Nausea; Vomiting

Keywords

autologous; myeloma; transplant

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  no emesis and no rescue anti-emetic therapy

  within 120 hours following melphalan administration; no emesis and no rescue therapy within 120 hours of melphalan administration (within 120 hours following last day of melphalan administration at baseline)

Secondary Outcomes (2)

• Acute Complete Response

  0 (transplant time) to 24 hours post-transplant

• Delayed Complete Response

  25-120 hours post-transplant

Study Arms (3)

Aprepitant

ACTIVE COMPARATOR

aprepitant plus standard anti-emetic regimen

Drug: o Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1

Olanzapine

EXPERIMENTAL

olanzapine plus standard anti-emetic regimen

Drug: Olanzapine10 mg orally daily on Days -1,0,+1 and +2

Aprepitant plus olanzapine

EXPERIMENTAL

aprepitant and olanzapine plus standard anti-emetic regimen

Drug: Aprepitant plus Olanzapine

Interventions

o Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1 DRUG

Add aprepitant to anti-emetic regimen

Also known as: Emend

Aprepitant

Olanzapine10 mg orally daily on Days -1,0,+1 and +2 DRUG

add olanzapine to anti-emetic regimen

Also known as: Zyprexa

Olanzapine

Aprepitant plus Olanzapine DRUG

add aprepitant and olanzapine to anti-emetic regimen

Also known as: Emend, Zyprexa

Aprepitant plus olanzapine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Autologous transplant containing high dose melphalan as part of the conditioning regimen (single or 2 day melphalan; BEAM \[carmustine, etoposide, cytarabine, melphalan\])
• able to tolerate oral medications

You may not qualify if:

• Nausea/vomiting within 12 hours before planned high dose conditioning chemotherapy
• Any anti-emetic treatment within 24 hours before planned high dose conditioning chemotherapy
• Pregnancy
• Baseline corrected QT interval (QTc) \> 500 ms
• History of seizures
• History of central nervous system (CNS) disease
• Human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (14)

• Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, Chesney M, Clark-Snow RA, Flaherty AM, Freundlich B, Morrow G, Rao KV, Schwartz RN, Lyman GH; American Society of Clinical Oncology. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011 Nov 1;29(31):4189-98. doi: 10.1200/JCO.2010.34.4614. Epub 2011 Sep 26.

  PMID: 21947834 BACKGROUND

• Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011 Sep-Oct;9(5):188-95. doi: 10.1016/j.suponc.2011.05.002. Epub 2011 Sep 24.

  PMID: 22024310 BACKGROUND

• Giralt SA, Mangan KF, Maziarz RT, Bubalo JS, Beveridge R, Hurd DD, Mendoza FL, Rubenstein EB, DeGroot TJ, Schuster MW. Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation. Ann Oncol. 2011 Apr;22(4):939-946. doi: 10.1093/annonc/mdq457. Epub 2010 Oct 8.

  PMID: 20935058 BACKGROUND

• Slaby J, Trneny M, Prochazka B, Klener P. Antiemetic efficacy of three serotonin antagonists during high-dose chemotherapy and autologous stem cell transplantation in malignant lymphoma. Neoplasma. 2000;47(5):319-22.

  PMID: 11130251 BACKGROUND

• Ballen KK, Hesketh AM, Heyes C, Becker PS, Emmons RV, Fogarty K, LaPointe J, Liu Q, Hsieh CC, Hesketh PJ. Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support. Bone Marrow Transplant. 2001 Dec;28(11):1061-6. doi: 10.1038/sj.bmt.1703280.

  PMID: 11781617 BACKGROUND

• Einhorn LH, Grunberg SM, Rapoport B, Rittenberg C, Feyer P. Antiemetic therapy for multiple-day chemotherapy and additional topics consisting of rescue antiemetics and high-dose chemotherapy with stem cell transplant: review and consensus statement. Support Care Cancer. 2011 Mar;19 Suppl 1:S1-4. doi: 10.1007/s00520-010-0920-z. Epub 2010 May 26.

  PMID: 20505956 BACKGROUND

• Jordan K, Jahn F, Jahn P, Behlendorf T, Stein A, Ruessel J, Kegel T, Schmoll HJ. The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant. 2011 Jun;46(6):784-9. doi: 10.1038/bmt.2010.205. Epub 2010 Sep 13.

  PMID: 20838387 BACKGROUND

• Pielichowski W, Barzal J, Gawronski K, Mlot B, Oborska S, Wasko-Grabowska A, Rzepecki P. A triple-drug combination to prevent nausea and vomiting following BEAM chemotherapy before autologous hematopoietic stem cell transplantation. Transplant Proc. 2011 Oct;43(8):3107-10. doi: 10.1016/j.transproceed.2011.08.010.

  PMID: 21996238 BACKGROUND

• Stiff PJ, Fox-Geiman MP, Kiley K, Rychlik K, Parthasarathy M, Fletcher-Gonzalez D, Porter N, Go A, Smith SE, Rodriguez TE. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013 Jan;19(1):49-55.e1. doi: 10.1016/j.bbmt.2012.07.019. Epub 2012 Aug 1.

  PMID: 22863840 BACKGROUND

• Khojainova N, Santiago-Palma J, Kornick C, Breitbart W, Gonzales GR. Olanzapine in the management of cancer pain. J Pain Symptom Manage. 2002 Apr;23(4):346-50. doi: 10.1016/s0885-3924(02)00378-0.

  PMID: 11997204 BACKGROUND

• Bymaster FP, Falcone JF, Bauzon D, Kennedy JS, Schenck K, DeLapp NW, Cohen ML. Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol. 2001 Nov 2;430(2-3):341-9. doi: 10.1016/s0014-2999(01)01399-1.

  PMID: 11711053 BACKGROUND

• Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients' quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006 Sep 20;24(27):4472-8. doi: 10.1200/JCO.2006.05.6382.

  PMID: 16983116 BACKGROUND

• 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.

  PMID: 25225424 BACKGROUND

• Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C. Assessing the impact of chemotherapy-induced nausea and vomiting on patients' daily lives: a modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall. Support Care Cancer. 2003 Aug;11(8):522-7. doi: 10.1007/s00520-003-0482-4. Epub 2003 Jun 25.

  PMID: 12827483 BACKGROUND

Related Links

• Multinational Association Of Supportive Care In Cancer (MASCC)/European Society of Medical Oncology (ESMO) Antiemetic Guidelines 2013

MeSH Terms

Conditions

Nausea; Vomiting; Neoplasms, Plasma Cell

Interventions

Aprepitant; Olanzapine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Danielle Murphy, PharmD, BCOP, BCPS
• Organization: Rush University Medical Center

danielle_murphy@rush.edu

3129472401

Study Officials

• Kathryn Schultz, PharmD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 20, 2016
• Study Start: September 23, 2017
• Primary Completion: December 30, 2021
• Study Completion: December 1, 2022
• Last Updated: October 22, 2024
• Results First Posted: January 22, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)