Odansetron and Dexamethasone Alone vs. Odansetron, Dexamethason and Apreptant to Prevent Nausea

Study Overview
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Brief Summary
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The purpose of this study is to compare two different treatment protocols for treating nausea and vomiting in patients who have undergone bone marrow transplant. Patients will be assigned to one of two treatment groups. The first group will recieve ondansetron (Zofran) tablets combined with a medicine called dexamethasone given IV. Both of these drugs are commercially available. Patients in the second treatment consists of the first two drugs, plus a newly approved drug known as aprepitant (MK-869, Emend). This combination will be the treatment being tested. The combination is approved by the FDA for chemotherapy regimens known to cause a lot of nausea and vomiting. It significantly decreases the delayed (more than 24 hours after therapy) nausea and vomiting seen with these regimens.

Detailed Description
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This will be a single center, comparative, randomized, double-blind, phase III trial designed to evaluate the efficacy of the NK-1 antagonist, aprepitant (MK-869), in combination with ondansetron and dexamethasone in the prevention of acute and delayed nausea and vomiting compared to ondansetron and dexamethasone in patients receiving highly emetogenic preparative regimens prior to autologous or allogeneic (related and unrelated) stem cell transplantation. Patients will be randomized to one of two treatments: dexamethasone 10 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day vs. 7.5 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day combined with aprepitant, 125 mg orally on the first day of their preparative regimen followed by 80 mg daily on each remaining day of the preparative regimen plus three additional days.

Official Title
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Prevention of Nausea and Vomitting Associated With Stem Cell Transplant: Results of a Prospective, Randomized Trial of Aprepitant Used With Highly Emetogenic Preparative Regimens

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: Standard PO (Zofran + Dexamethason)
* Drug: Aprepitant (MK-869) + Standard PO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer, admitted for myelosupppresive stem cell transplantation. Included preparative regimens include: TBI/VP16/CY, TBI/CY, BU/CY (PO & IV), and BCV Age 18 or older Alcohol intake <100 gm/d for the last year (< approximately 5 drinks per day) Renal function: estimated or measured CrCl 50 ml/min Liver function: T.Bili <1.5, AST < 2x ULN, unless due to disease Able to swallow tablets and capsules Exclusion Criteria: Age < 18 High alcohol intake [> 100 gm/d in the last year] Allergy or intolerance to: ondansetron or dexamethasone Renal dysfunction [measured or estimated CrCl < 50 ml/min] Liver dysfunction [T.Bili > 1.5, AST > 2x ULN, unless due to disease] Inability to swallow tablets or capsules Concurrent condition requiring systemic steroid use Nonmyeloablative SCT, patients receiving the conditioning regimens not included [see inclusion criteria] History of anticipatory nausea and vomiting

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard PO (Zofran + Dexamethasone)<br>Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron (Zofran) 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion. | Drug: Standard PO (Zofran + Dexamethason)<br>* Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion. A placebo capsule will be given daily on each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.<br>* Other names: Ondansetron (Zofran);|
| Active Comparator: Aprepitant (MK-869) + Standard PO<br>Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO [blinded] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO [blinded] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen. | Drug: Aprepitant (MK-869) + Standard PO<br>* Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO [blinded] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO [blinded] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.<br>* Other names: Ondansetron + Dexamethason (Standard PO);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rates Among Standard of Care and Combination Therapy Groups. | Comparison of complete response (CR) rates between patients receiving ondansetron and dexamethasone and those receiving ondansetron and dexamethasone plus NK-1 antagonist, aprepitant. CR is defined as no emesis and with normal oral intake. Disease response not applicable. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Marrow Transplant, Nausea, Vomiting, NK-1 antagonist