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

NCT ID: NCT02939287

Last Updated: 2024-10-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-23

Study Completion Date

2022-12-01

Brief Summary

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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

Detailed Description

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This is a multi-center, randomized, non-inferiority phase 3 study conducted to determine an appropriate anti-emetic regimen for patients receiving melphalan for an autologous stem cell transplant (SCT). Candidates for this trial will include patients aged 18-80 years with hematologic malignancies receiving high dose melphalan as part of a conditioning regimen for an autologous stem cell transplant. Patients will be enrolled in 3 arms. Patients in Arm A will receive an aprepitant containing anti-emetic regimen. Patients in Arm B will receive an olanzapine containing anti-emetic regimen. Patients in Arm C will receive an aprepitant plus olanzapine containing anti-emetic regimen. Patients must be able to tolerate oral medications.

Patients will be carefully monitored for rates of emesis, nausea, and mucositis. Any adverse events will be recorded. Impact on quality of life will also be assessed. A total of 184 patients will be accrued to each arm. It is anticipated that the accrual period will last approximately 2-3 years. The primary endpoint of this study is a complete response, defined as no emesis and no rescue therapy within 120 hours of melphalan administration.

Conditions

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Nausea Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Aprepitant

aprepitant plus standard anti-emetic regimen

Group Type ACTIVE_COMPARATOR

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

Intervention Type DRUG

Add aprepitant to anti-emetic regimen

Olanzapine

olanzapine plus standard anti-emetic regimen

Group Type EXPERIMENTAL

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

Intervention Type DRUG

add olanzapine to anti-emetic regimen

Aprepitant plus olanzapine

aprepitant and olanzapine plus standard anti-emetic regimen

Group Type EXPERIMENTAL

Aprepitant plus Olanzapine

Intervention Type DRUG

add aprepitant and olanzapine to anti-emetic regimen

Interventions

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

Add aprepitant to anti-emetic regimen

Intervention Type DRUG

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

add olanzapine to anti-emetic regimen

Intervention Type DRUG

Aprepitant plus Olanzapine

add aprepitant and olanzapine to anti-emetic regimen

Intervention Type DRUG

Other Intervention Names

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Emend Zyprexa Emend Zyprexa

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rush University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathryn Schultz, PharmD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Locations

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Rush University Medical Center

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21947834 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22024310 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20935058 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11130251 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11781617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20505956 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20838387 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21996238 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22863840 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11997204 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11711053 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16983116 (View on PubMed)

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 BACKGROUND
PMID: 25225424 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12827483 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

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https://mascc.org

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

Other Identifiers

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14102001

Identifier Type: -

Identifier Source: org_study_id

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