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

Augusta University

Status and phase: Completed; Phase 3

Conditions: Hematologic Neoplasms; Complications of Bone Marrow Transplant

Treatments: Drug: Olanzapine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02635984

818888

Details and patient eligibility

About

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.

Full 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.

Enrollment: 108 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

108 participants in 2 patient groups, including a placebo group

Triplet Therapy Plus Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Triplet Therapy Plus Olanzapine

Active Comparator group

Description:

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.

Treatment:

Drug: Olanzapine