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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02635984

Acronym

FOND-O

Enrollment

108

Registered

2015-12-21

Start date

2015-11-30

Completion date

2017-12-31

Last updated

2018-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Complications of Bone Marrow Transplant, Hematologic Neoplasms

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.

Interventions

DRUGOlanzapine

Olanzapine 10mg by mouth once daily on all chemotherapy days and for three days post-chemotherapy

DRUGPlacebo

Placebo tablet taken by mouth once daily on chemotherapy days and for 3 days post chemotherapy

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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)
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Placebo: Placebo tablet taken by mouth once daily on chemotherapy days and for 3 days post chemotherapy	50
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. Olanzapine: Olanzapine 10mg by mouth once daily on all chemotherapy days and for three days post-chemotherapy	51
Total	101

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	2	4
Overall Study	Study Arm Closed	1	0

Baseline characteristics

Characteristic	Triplet Therapy Plus Placebo	Triplet Therapy Plus Olanzapine	Total
Age, Continuous	56 years	54 years	55 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	19 Participants	21 Participants	40 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	3 Participants	5 Participants
Race (NIH/OMB) White	29 Participants	27 Participants	56 Participants
Sex: Female, Male Female	31 Participants	29 Participants	60 Participants
Sex: Female, Male Male	19 Participants	22 Participants	41 Participants
Treatment Regimen Chemotherapy Alone	16 Participants	17 Participants	33 Participants
Treatment Regimen HCT Conditioning	34 Participants	34 Participants	68 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0
other Total, other adverse events	3 / 50	0 / 51
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

Primary

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.