Study of FOND Versus FOND+O for the Prevention of CINV in Hematology Patients Receiving Highly Emetogenic Chemotherapy Regimens (FOND-O)

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

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Neoplasms; Complications of Bone Marrow Transplant
• Intervention / Treatment: Drug: Placebo; Drug: Olanzapine

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Triplet Therapy Plus Placebo; All subjects will receive standard triplet antiemetic therapy which consists of ondansetron and dexamethasone on each day of chemotherapy plus fosaprepitant 150 mg IV once per national guidelines for CINV prophylaxis. In addition to those antiemetics, subjects will receive placebo on all chemotherapy days and for three additional days post chemotherapy.	Drug: Placebo; Placebo tablet taken by mouth once daily on chemotherapy days and for 3 days post chemotherapy
Active Comparator: Triplet Therapy Plus Olanzapine; All subjects will receive standard triplet antiemetic therapy which consists of ondansetron and dexamethasone on each day of chemotherapy plus fosaprepitant 150 mg IV once per national guidelines for CINV prophylaxis. In addition to those antiemetics, subjects will receive olanzapine 10mg orally on all chemotherapy days and for three additional days post chemotherapy.	Drug: Olanzapine; Olanzapine 10mg by mouth once daily on all chemotherapy days and for three days post-chemotherapy; Other Names: Zyprexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Percentage of Patients Who Had a Complete Response	Overall percentage of patients who had a complete response (CR) defined as no emesis and minimal nausea (< 25 mm on a 100 mm visual analog scale [VAS]) during the overall assessment period (starting day 1 of chemotherapy and continuing for 5 days after discontinuation of chemotherapy) for the first cycle of chemotherapy.	Until study completion; estimated 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients With no Significant Nausea in Overall Assessment Period	Reported for overall phases [chemotherapy days plus 5 days after] where all VAS < 25 mm	Until study completion; estimated 1.5 years
Percent of Patients Achieving Complete Protection in Overall Assessment Phase	(CP = no emesis, no breakthrough antiemetic use, no significant nausea). To be reported as overall phases [chemotherapy days plus 5 days after]	Until study completion; estimated 1.5 years
Percent of Participants With no Significant Nausea in Acute Phase	Reported as acute [chemotherapy days]. All assessment with all VAS < 25 mm on days of chemotherapy	Until study completion; estimated 1.5 years
Percent of Participants With no Significant Nausea in Delayed Phase	Reported for delayed [5 days after chemotherapy administration] All assessment with all VAS < 25 mm	Until study completion; estimated 1.5 years
Percent of Patients With no Nausea in Overall Assessment Period	No nausea (all VAS <5 mm) in overall assessment period (days of chemotherapy plus five days after)	Until study completion; estimated 1.5 years
Percent of Patients With Complete Response in Acute Phase	Complete response (no emesis and no more than minimal nausea, defined as < 25 mm on a 100 mm visual analog scale [VAS]) in acute phase (days of chemotherapy)	Until study completion; estimated 1.5 years
Percent of Patients With Complete Response in Delayed Phase	Complete response (no emesis and no more than minimal nausea, defined as < 25 mm on a 100 mm visual analog scale [VAS]) in delayed phase (5 days after chemotherapy)	Until study completion; estimated 1.5 years

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: University of Georgia
• Investigators: Principal Investigator: Amber B Clemmons, PharmD, Augusta University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimate): December 21, 2015

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: July 18, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: 818888

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO