Clinical trial NCT02635984: Study of FOND Versus FOND+O for the Prevention of CINV in Hematology Patients Receiving Highly Emetogenic Chemotherapy Regimens
Official title: Randomized, Placebo Controlled Study of FOND (Fosaprepitant, Ondansetron, Dexamethasone) Versus FOND+O (FOND Plus Olanzapine) for the Prevention of Chemotherapy Induced Nausea and Vomiting in Hematology Patients Receiving Highly Emetogenic Chemotherapy Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complications of Bone Marrow Transplant
Hematologic Neoplasms
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: University of Georgia
First posted: 2015-12-21
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The objective of this study is to compare the effectiveness of olanzapine added to standard triplet therapy (fosaprepitant, ondansetron, and dexamethasone) versus triplet therapy alone in preventing chemotherapy-induced nausea and vomiting (CINV) in hematology patients receiving highly or moderately emetogenic chemotherapy regimens.

Detailed description: Nausea and vomiting remains a common and difficult to manage consequence of chemotherapy despite prophylaxis. These symptoms can often lead to a decreased quality of life, dehydration, and malnutrition. Olanzapine is an atypical antipsychotic that blocks multiple neuronal receptors involved in nausea/vomiting pathways. Olanzapine has been studied for breakthrough chemo-induced nausea and vomiting (CINV) as well as in prophylaxis of highly and moderately emetogenic regimens (HEC and MEC, respectively). However, these studies have focused on patients with solid tumor malignancies and chemotherapy regimens of short duration. To date, no publications have reported outcomes from adding olanzapine to standard triplet therapy, for hematology patients, including those undergoing hematopoietic stem cell transplants and those who receive multi-day HEC and MEC regimens.

This is a blinded, placebo controlled trial randomizing patients to receive olanzapine 10 mg orally on all chemotherapy days plus three additional days post chemotherapy or placebo in addition to standard triplet therapy (ondansetron and dexamethasone on each day of chemotherapy and fosaprepitant 150 mg IV on day one of chemotherapy). Inclusion criteria: age 18 or older, receiving inpatient or outpatient HEC or MEC chemotherapy including those regimens given before stem cell transplantation (ABVD, ICE ± R, 7+3 or 5+2, BEAM, Bu/Cy ± ATG, Bu/Flu ± ATG, FluCy ± ATG, BuMel, FluBuCy, Melphalan). Exclusion criteria: allergy to olanzapine, documented nausea/vomiting ≤24 hours before enrollment, treatment with other antipsychotic agents, or declined informed consent. Patients will be randomized to placebo or olanzapine in a block design stratified by chemotherapy type (transplant conditioning vs. chemotherapy only) and number of days of chemotherapy (single vs. multi-day) by the Investigational Drug Pharmacy services at Augusta University Medical Center.

Eligibility criteria: Inclusion Criteria:

* Inpatient or outpatient hematology patient receiving one of the following regimens:
* Chemotherapy for hematologic malignancy:
* ABVD
* ICE ± R
* 7+3
* Conditioning therapy for stem cell transplantation:
* BEAM
* Bu/Cy ± ATG
* Bu/Flu ± ATG
* FluCy ± ATG
* FluCy + TBI
* BuMel
* FluBuCy
* Melphalan
* Etoposide + TBI
* Cyclophosphamide + TBI

Exclusion Criteria:

* Allergy to olanzapine
* Documented nausea or vomiting ≤24 hours prior to enrollment
* Treatment with other antipsychotic agents such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone ≤30 days prior to enrollment or planned during protocol therapy
* Chronic alcoholism
* Pregnant
* Declined or unable to provide an informed consent

Primary outcomes:
measure: Overall Percentage of Patients Who Had a Complete Response
timeFrame: Until study completion; estimated 1.5 years
Secondary outcomes:
measure: Percent of Patients With no Significant Nausea in Overall Assessment Period
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Patients Achieving Complete Protection in Overall Assessment Phase
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Participants With no Significant Nausea in Acute Phase
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Participants With no Significant Nausea in Delayed Phase
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Patients With no Nausea in Overall Assessment Period
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Patients With Complete Response in Acute Phase
timeFrame: Until study completion; estimated 1.5 years
measure: Percent of Patients With Complete Response in Delayed Phase
timeFrame: Until study completion; estimated 1.5 years
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
Study officials:
affiliation: Augusta University Medical Center
name: Amber B Clemmons, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clemmons AB, Orr J, Andrick B, Gandhi A, Sportes C, DeRemer D. Randomized, Placebo-Controlled, Phase III Trial of Fosaprepitant, Ondansetron, Dexamethasone (FOND) Versus FOND Plus Olanzapine (FOND-O) for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Highly Emetogenic Chemotherapy and Hematopoietic Cell Transplantation Regimens: The FOND-O Trial. Biol Blood Marrow Transplant. 2018 Oct;24(10):2065-2071. doi: 10.1016/j.bbmt.2018.06.005. Epub 2018 Jun 13.