This phase II trial studies how well netupitant and palonosetron hydrochloride work in preventing chemotherapy induced nausea and vomiting in patients with cancer undergoing BEAM conditioning regimen before stem cell transplant. Chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), makes people feel sick to their stomach and causes vomiting. Netupitant and palonosetron hydrochloride may reduce the nausea and vomiting caused by the BEAM treatment.

PRIMARY OBJECTIVES:

I. To assess the efficacy of netupitant and palonosetron hydrochloride (NEPA) to prevent nausea and vomiting both during and after a highly emetogenic (BEAM) conditioning regimen for hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVES:

I. To differentiate response to NEPA over different phases of chemotherapy-induced nausea.

OUTLINE:

Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride orally (PO) on days 1, 3, and 6.

After completion of study treatment, patients are followed up at 14 days.

Inclusion Criteria:

• Subjects must be undergoing autologous or allogeneic hematopoietic stem cell transplant (HSCT) with the BEAM conditioning regimen prior to HSCT
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky Performance Score >= 60%
• Able to swallow oral medications
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Subjects with known hypersensitivity or other allergic reactions attributed to compounds of similar biologic composition to netupitant, palonosetron, dexamethasone, or other agents used in the study
• Subjects who are receiving any other investigational agents or have received another investigational drug in the last 30 days
• Subjects who have had emesis or required antiemetics in the 48 hours prior to starting the BEAM conditioning regimen; patients required to take antipsychotics, appetite stimulants, or other medications with antiemetic effects will also be excluded if those medications cannot be replaced by therapeutic equivalents
• Female subjects who are pregnant, have a positive serum human chorionic gonadotrophin (hCG), or are lactating and intend to breastfeed a child; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with NEPA
• Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
• Subjects who have taken a neurokinin antagonist within 14 days prior to beginning the BEAM regimen
• Subjects who have a serum creatinine > 2 x upper limit of normal (ULN)
• Subjects with severe renal failure or end stage renal disease (estimated GFR [glomerular filtration rate] of < 30 mL/min) as estimated by the Cockcroft-Gault formula
• Subjects with severe hepatic insufficiency (Child Pugh score > 9)
• Subjects who have been reported > 5 alcoholic drinks daily for the last year
• Subjects who have concurrent illness requiring systemic corticosteroid use other than the planned dexamethasone during conditioning therapy
• Subjects with gastrointestinal conditions that might result in malabsorption of the study drug
• Subjects with a history of anxiety-induced ("anticipatory") nausea and vomiting
• Subjects on strong CYP 3A4 inducers or inhibitors who are unable to have those agents replaced with clinical alternatives prior to beginning the study; length of washout period will be 7 days; notably, in the case of allogeneic transplant recipients requiring cyclosporine or tacrolimus, no empiric dose adjustments will be required due to close level monitoring and adjustments, that are standard in Oregon Health & Science University (OHSU) protocols
• Subjects unable to discontinue benzodiazepines as antiemetics will not be allowed; additional antiemetics will be allowed for rescue but not for prophylaxis
• Subjects with personal or family history of QT prolongation, uncorrected electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and those taking antiarrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities; relevant information will be collected as part of subject medical history