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

Study Overview
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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.

Official Title
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Aprepitant- and Olanzapine- Containing Regimens for Prevention of Acute and Delayed Nausea and Vomiting Associated With High Dose Melphalan and BEAM in Autologous Stem Cell Transplant Patients

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: Aprepitant
* Drug: Olanzapine
* Drug: Aprepitant plus Olanzapine


Participation Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aprepitant<br>aprepitant plus standard anti-emetic regimen | Drug: Aprepitant<br>* Add aprepitant to anti-emetic regimen<br>* Other names: Emend;|
| Experimental: Olanzapine<br>olanzapine plus standard anti-emetic regimen | Drug: Olanzapine<br>* add olanzapine to anti-emetic regimen<br>* Other names: Zyprexa;|
| Experimental: Aprepitant plus olanzapine<br>aprepitant and olanzapine plus standard anti-emetic regimen | Drug: Aprepitant plus Olanzapine<br>* add aprepitant and olanzapine to anti-emetic regimen<br>* Other names: Zyprexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response (CR) | no emesis and no rescue anti-emetic therapy | within 120 hours following melphalan administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute complete response | no emesis or rescue therapy | 0 to 24 hours | 
| Delayed complete response | no emesis or rescue therapy | 25-120 hours | 
| Very delayed complete response | no emesis or rescue therapy | 121-168 hours | 
| Mucositis/Significant mucositis |  | up to 14 days | 
| Time to neutrophil engraftment |  | up to 14 days | 
| Time to platelet engraftment |  | up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous, myeloma, transplant