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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Complications of Bone Marrow Transplant, Hematologic Neoplasms

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Triplet Therapy Plus Placebo<br>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<br>* Placebo tablet taken by mouth once daily on chemotherapy days and for 3 days post chemotherapy<br>|
| Active Comparator: Triplet Therapy Plus Olanzapine<br>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<br>* Olanzapine 10mg by mouth once daily on all chemotherapy days and for three days post-chemotherapy<br>* Other names: Zyprexa;|

What is the study measuring?
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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 |