Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients With Cancer Undergoing BEAM Conditioning Regimen Before Stem Cell Transplant

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 cell transplant
(HSCT) with the BEAM conditioning regimen prior to HSCT

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- 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; also patients required to take antipsychotics, appetite
stimulants, or other medications with antiemetic effects will 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 breast feed 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 drinking > 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 which 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, which are standard in Oregon Health &
Science University (OHSU) protocols

- Subjects unable to discontinue benzodiazepines will not be allowed as hypnotics;
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 during medical history taking