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

Phase 3

Completed

• Conditions: Complications of Bone Marrow Transplant; Hematologic Neoplasms
• Interventions: Drug: Placebo; Drug: Olanzapine

• Registration Number: NCT02635984
• Lead Sponsor: Augusta University

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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2015-12-15
• Study First Submitted QC: 2015-12-16
• Study First Posted: 2015-12-21
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Results First Submitted: 2018-06-22
• Status Verified: 2018-07
• Results First Submitted QC: 2018-07-18
• Last Update Submitted: 2018-07-18
• Results First Posted: 2018-08-20
• Last Update Posted: 2018-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 108

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Triplet Therapy Plus Placebo	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.
Triplet Therapy Plus Olanzapine	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.

Primary Outcome Measures

Name	Time	Method
Overall Percentage of Patients Who Had a Complete Response	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

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

Trial Locations

Locations (1)

Augusta University Medical Center; 🇺🇸 Augusta, Georgia, United States