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

Phase 3

Completed

• Conditions: Vomiting; Nausea
• Interventions: Drug: o Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1; Drug: Olanzapine10 mg orally daily on Days -1,0,+1 and +2; Drug: Aprepitant plus Olanzapine

• Registration Number: NCT02939287
• Lead Sponsor: Rush University Medical Center

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2016-10-18
• Study First Submitted QC: 2016-10-18
• Study First Posted: 2016-10-20
• Study Start: 2017-09-23
• Primary Completion: 2021-12-30
• Study Completion: 2022-12-01
• Results First Submitted: 2023-01-30
• Results First Submitted QC: 2024-01-18
• Results First Posted: 2024-01-22
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aprepitant	o Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1	aprepitant plus standard anti-emetic regimen
Olanzapine	Olanzapine10 mg orally daily on Days -1,0,+1 and +2	olanzapine plus standard anti-emetic regimen
Aprepitant plus olanzapine	Aprepitant plus Olanzapine	aprepitant and olanzapine plus standard anti-emetic regimen

Primary Outcome Measures

Name	Time	Method
Complete Response (CR)	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)	no emesis and no rescue anti-emetic therapy

Secondary Outcome Measures

Name	Time	Method
Delayed Complete Response	25-120 hours post-transplant	no emesis or rescue therapy administered; Delayed complete response defined as no emesis or rescue therapy required from time point of 25 hours to 120 hours following melphalan therapy administration
Acute Complete Response	0 (transplant time) to 24 hours post-transplant	no emesis or rescue therapy; Acute complete response defined as no emesis or rescue therapy required from time point of 0 to 24 hours following melphalan therapy administration

Trial Locations

Locations (1)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States