Olanzapine 2.5 vs 5 mg in Quadruplet Nausea/Vomiting Prophylaxis Before High-Dose Melphalan (FONDO-LOW)

Randomized, Double-Blind Study of FOND (Fosaprepitant, ONdansetron, Dexamethasone) Plus Either Olanzapine 2.5 mg Versus 5 mg for the Prevention of Chemotherapy Induced Nausea and Vomiting in Patients Receiving High-dose Melphalan Conditioning: The FONDO-LOW Study

Patients who receive a chemotherapy called melphalan are at high risk of having nausea and vomiting. A medication called olanzapine has been shown to decrease nausea and vomiting after chemotherapy. A previous research study found the 10 mg dose of olanzapine (combined with 3 standard medications used routinely to prevent nausea/vomiting) to be effective for patients who received melphalan chemotherapy, but several other studies have shown many patients have a side effect of sleepiness (e.g., sedation) with that dose of the medication. Our study will compare two lower doses of olanzapine (5 mg and 2.5 mg) in combination with the 3 standard medications used to prevent nausea/vomiting in the patients who receive melphalan chemotherapy to determine which dose is effective in preventing nausea and vomiting with the lowest amount of sleepiness side effect.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Autologous Stem Cell Transplantation
• Intervention / Treatment: Drug: Olanzapine

Detailed Description

This study is a randomized, double-blinded trial comparing olanzapine 2.5 mg vs 5 mg in combination with standard triplet antiemetic prophylaxis in patients with multiple myeloma who are receiving high-dose melphalan conditioning chemotherapy before autologous stem cell transplantation to determine chemotherapy-induced nausea and vomiting (CINV) and sedation outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amber Clemmons, PharmD, BCOP, FHOPA; Phone Number: 706-721-6493; Email: aclemmons@augusta.edu

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Wellstar MCG
      • Contact: Amber Clemmons, PharmD; Phone Number: 706-721-6493; Email: aclemmons@augusta.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Receipt of high-dose melphalan 140-200 mg/m2
• Autologous stem cell transplantation recipient

Exclusion Criteria:

• Allergy to olanzapine
• Documented nausea or vomiting within 24 hours prior to enrollment
• Treatment with other antipsychotic agents such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone within 30 days prior to enrollment or planned during protocol therapy
• Chronic alcoholism
• Pregnant
• Decline or unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olanzapine 2.5 mg; Olanzapine 2.5 mg dose to be given on the day of high-dose melphalan and three days after	Drug: Olanzapine; Subjects will be randomized to either olanzapine 2.5 mg or 5 mg; Other Names: Zyprexa
Active Comparator: Olanzapine 5 mg; Olanzapine 5 mg dose to be given on the day of high-dose melphalan and three days after	Drug: Olanzapine; Subjects will be randomized to either olanzapine 2.5 mg or 5 mg; Other Names: Zyprexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response	The primary objective is to compare the percentage of patients achieving chemotherapy-induced nausea and vomiting (CINV) complete response (CR), where CR is defined as no emesis and no more than mild nausea (</=1 score on a 4-point categorical scale [0 = none, 1 = mild, 2 = moderate, and 3 = severe]) during the overall assessment period (defined as the day of chemotherapy through 5 days after chemotherapy).	From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Protection	Complete protection (CP) defined as no emesis, no more than mild nausea, and no use of breakthrough antiemetic agents	From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)
Incidence of patients with no more than minimal sedation		From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)
Incidence of patients with no more than minimal nausea		From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)
Number of emetic episodes		From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)
Number of breakthrough antiemetic doses		From day of chemotherapy (acute phase) through 5 days after chemotherapy (delayed phase)

Collaborators and Investigators

• Sponsor: Augusta University

Publications and helpful links

General Publications

• 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.
• Bajpai J, Kapu V, Rath S, Kumar S, Sekar A, Patil P, Siddiqui A, Anne S, Pawar A, Srinivas S, Bhargava P, Gulia S, Noronha V, Joshi A, Prabhash K, Banavali S, Sarin R, Badwe R, Gupta S. Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial. Lancet Oncol. 2024 Feb;25(2):246-254. doi: 10.1016/S1470-2045(23)00628-9. Epub 2024 Jan 12.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Nausea; Melphalan; Olanzapine; autologous transplant; CINV
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Signs and Symptoms, Digestive; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Nausea; Vomiting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antipsychotic Agents; Olanzapine
• Other Study ID Numbers: 2216424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No