Olanzapine for Nausea/Vomiting Prophylaxis in Recipients of Hematopoietic Stem Cell Transplants

NCT04535141 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: LCCC203720-0833
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to see if olanzapine helps to prevent nausea and/or vomiting (throwing up) when it is added to other medicines in subjects having stem cell transplants. Subjects will either be given olanzapine or an inactive pill (called a placebo) before getting any chemotherapy that is known to cause nausea and vomiting. During the study, the study coordinators will ask the subjects to complete surveys to understand if the patient is having nausea and vomiting, and if so, how bad it is making the patient feel. This trial will split subjects into two groups: one group will be given an inactive pill (placebo), and the other group will be given the active pill (olanzapine). Study coordinators will collect surveys every morning before chemotherapy and 5 days after the last dose of chemotherapy. These surveys may be given by members of the study team or possibly on a mobile device. Subjects may benefit from being in this research study because olanzapine may reduce the frequency or severity of chemotherapy-induced nausea and vomiting (CINV). The most common risks of using olanzapine include possibly becoming more tired, mild dizziness, mild low blood pressure, and mild muscle "quivering." Other possible adverse effects include low blood pressure, muscle weakness, increased appetite, weight gain, constipation, and liver function test changes however these risks are less common in subjects with cancer. In addition, there may be a change detected in heart rhythm however subjects will be screened for this ahead of time.

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

Chemotherapy-induced Nausea and Vomiting; Chemotherapy; Nausea and Vomiting; Olanzapine

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Response

  The number of subjects who completed the study and the overall rate of complete response were assessed. Complete response achievement requires all three of the following criteria for the entire duration of the study assessment period: 1. No emesis, 2. Response to PRO-CTCAE question "In the last 24 hours, how often did you have nausea?" is no higher than rarely and 3. Response to PRO-CTCAE question "In the last 24 hours, what was the severity of your nausea at its worst? a score no higher than "mild".

  End of study assessment period, until 5 days after last chemotherapy administration (2- 12 days)

Secondary Outcomes (10)

• Total Number of Rescue Medications Needed Acute

  End of day 1 following last chemotherapy administration. (Up to day 2)

• Number of Subjects Achieving Minimal Nausea

  Day 2-12

• Frequency of Nausea in the Acute Phase

  End of day 1 following last chemotherapy administration (Up to day 2)

• Number of Subjects Achieved Emesis Endpoint in Acute Phase.

  End of day 1 following last chemotherapy administration. (Up to day 2)

• Frequency of Somnolence

  Day 2-12

Study Arms (2)

Olanzapine Arm

EXPERIMENTAL

Olanzapine 5mg tablet with chemotherapy, and 3 days after

Drug: Olanzapine 5 MG

Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Olanzapine 5 MG DRUG

It will be a de-identified pill created by investigational drug services at University of North Carolina

Also known as: Zyprexa

Olanzapine Arm

Placebo DRUG

It will be a de-identified pill created by investigational drug services at University of North Carolina

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information.
• Recipients receiving autologous or allogeneic HCT for any disease
• Any conditioning chemotherapy regimen considered a standard bone marrow transplantation conditioning regimen
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• The subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.

You may not qualify if:

• Patients must not have started conditioning chemotherapy prior to consent. Note: test dose Busulfan is not part of conditioning chemotherapy
• Known allergy to olanzapine
• Baseline corrected QT interval ( QTc )\>500 msec as calculated by the Fridericia formula
• Patients receiving post-transplant cyclophosphamide as planned graft-versus-host disease (GVHD) prophylaxis
• Pregnant or breastfeeding (NOTE: patients pregnant or breast-feeding are not eligible to proceed to transplant).
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Treatment with any investigational drug within 7 days prior to registration.
• Subject is receiving prohibited medications (ciprofloxacin or fluvoxamine) that cannot be discontinued/replaced by an alternative therapy.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• University of North Carolina, Chapel Hill: collaborator

Study Sites (1)

UNC Hospital

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (7)

• Monson T, Greer D, Kreikemeier E, Liewer S. Olanzapine as a rescue antiemetic in hematopoietic stem cell transplant. J Oncol Pharm Pract. 2020 Jun;26(4):918-922. doi: 10.1177/1078155219879215. Epub 2019 Oct 21.

  PMID: 31635549 BACKGROUND

• Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. doi: 10.1056/NEJMoa1515725.

  PMID: 27410922 BACKGROUND

• Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Somerfield MR, Lyman GH. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017 Oct 1;35(28):3240-3261. doi: 10.1200/JCO.2017.74.4789. Epub 2017 Jul 31.

  PMID: 28759346 BACKGROUND

• Trifilio S, Welles C, Seeger K, Mehta S, Fishman M, McGowan K, Strejcek K, Eiten E, Pirotte C, Lucier E, DeFrates S, Mehta J. Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study. Clin Lymphoma Myeloma Leuk. 2017 Sep;17(9):584-589. doi: 10.1016/j.clml.2017.06.012. Epub 2017 Jun 20.

  PMID: 28694084 BACKGROUND

• Navari RM, Aapro M. Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Apr 7;374(14):1356-67. doi: 10.1056/NEJMra1515442. No abstract available.

  PMID: 27050207 BACKGROUND

• 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.

  PMID: 29906570 BACKGROUND

• Basch E, Dueck AC, Rogak LJ, Mitchell SA, Minasian LM, Denicoff AM, Wind JK, Shaw MC, Heon N, Shi Q, Ginos B, Nelson GD, Meyers JP, Chang GJ, Mamon HJ, Weiser MR, Kolevska T, Reeve BB, Bruner DW, Schrag D. Feasibility of Implementing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048. J Clin Oncol. 2018 Sep 11;36(31):JCO2018788620. doi: 10.1200/JCO.2018.78.8620. Online ahead of print.

  PMID: 30204536 BACKGROUND

MeSH Terms

Conditions

Vomiting; Nausea

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jonathan Ptachcinski PharmD, BCPS, BCOP
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

Jonathan.Ptachcinski@unchealth.unc.edu

+1 919-966-9786

Study Officials

• Jonathan Ptachcinski, PharmD

  jonathan.Ptachcinski@unchealth.unc.edu

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: September 1, 2020
• Study Start: August 18, 2020
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: May 9, 2023
• Results First Posted: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)