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

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.

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)