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

• ClinicalTrials.gov Identifier: NCT02635984
• Recruitment Status: Completed
• First Posted: December 21, 2015
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Sponsor: Augusta University
• Collaborator: University of Georgia
• Information provided by (Responsible Party): Amber Clemmons, Augusta University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Complications of Bone Marrow Transplant; Hematologic Neoplasms	Drug: Olanzapine; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• 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
• Actual Study Start Date: November 2015
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: December 2017

Arms and Interventions

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 Name: Zyprexa

Outcome Measures

Primary Outcome Measures :

1. Overall Percentage of Patients Who Had a Complete Response [ Time Frame: Until study completion; estimated 1.5 years ]
   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.

Secondary Outcome Measures :

1. Percent of Patients With no Significant Nausea in Overall Assessment Period [ Time Frame: Until study completion; estimated 1.5 years ]
   Reported for overall phases [chemotherapy days plus 5 days after] where all VAS < 25 mm
2. Percent of Patients Achieving Complete Protection in Overall Assessment Phase [ Time Frame: Until study completion; estimated 1.5 years ]
   (CP = no emesis, no breakthrough antiemetic use, no significant nausea). To be reported as overall phases [chemotherapy days plus 5 days after]
3. Percent of Participants With no Significant Nausea in Acute Phase [ Time Frame: Until study completion; estimated 1.5 years ]
   Reported as acute [chemotherapy days]. All assessment with all VAS < 25 mm on days of chemotherapy
4. Percent of Participants With no Significant Nausea in Delayed Phase [ Time Frame: Until study completion; estimated 1.5 years ]
   Reported for delayed [5 days after chemotherapy administration] All assessment with all VAS < 25 mm
5. Percent of Patients With no Nausea in Overall Assessment Period [ Time Frame: Until study completion; estimated 1.5 years ]
   No nausea (all VAS <5 mm) in overall assessment period (days of chemotherapy plus five days after)
6. Percent of Patients With Complete Response in Acute Phase [ Time Frame: Until study completion; estimated 1.5 years ]
   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)
7. Percent of Patients With Complete Response in Delayed Phase [ Time Frame: Until study completion; estimated 1.5 years ]
   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)

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Georgia

Augusta University Medical Center

Augusta, Georgia, United States, 30912

Sponsors and Collaborators

Augusta University

University of Georgia

Investigators

• Principal Investigator: Amber B Clemmons, PharmD; Augusta University Medical Center

  Study Documents (Full-Text)

Documents provided by Amber Clemmons, Augusta University:

Study Protocol and Statistical Analysis Plan  [PDF] July 11, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Amber Clemmons, Pharmacist, Augusta University
• ClinicalTrials.gov Identifier: NCT02635984
• Other Study ID Numbers: 818888
• First Posted: December 21, 2015
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Hematologic Diseases; Olanzapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents