Chemotherapy-induced Nausea and VomitingPhase 3NCT04535141
Olanzapine for Nausea/Vomiting Prophylaxis in Recipients of Hematopoietic Stem Cell Transplants
A Phase 3 study testing Olanzapine 5 MG in people with Chemotherapy-induced Nausea and Vomiting, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemotherapy-induced Nausea and Vomiting
- What is being tested?
- Olanzapine 5 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Aug 2020to 11 Apr 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Addition of Olanzapine to Standard CINV Prophylaxis in Hematopoietic Stem Cell Transplant
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.
Read the detailed description
Chemotherapy induced nausea and vomiting (CINV) occurs in up to 80% of patients on active therapy and remains a significant barrier to quality of life. CINV can alter electrolytes and enteral nutrition which can have a detrimental effect on patient adherence and health outcomes. Hematopoietic Stem Cell Transplant (HCT) patients are at increased risk for CINV because many of the conditioning regimens require multiple days of high-dose chemotherapy that are, in many cases, associated with highly-emetogenic potential.
Thus, most conditioning regimens require a 3-drug regimen for optimal CINV prophylaxis.
Current Standard of Care Current guidelines support the use of olanzapine in addition to a 3 drug CINV regimen for highly emetogenic chemotherapy, however some controversy remains as to olanzapine's place in therapy with moderately emetogenic chemotherapy. In HCT, current practice at University of North Carolina utilizes an neurokinin-1 receptor antagonist (NK1 RA), serotonin receptor antagonists (5-HT3 RA) and corticosteroid for CINV prophylaxis in conditioning regimens including moderate and highly emetogenic chemotherapy in accordance with American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommendations.
Olanzapine, an atypical antipsychotic, antagonizes dopamine, serotonin, catecholamines, acetylcholine, and histamine receptors which helps prevent acute, breakthrough and delayed nausea. Olanzapine has shown benefit when used as prophylaxis in solid tumor patients receiving single-day highly emetogenic chemotherapy. The addition of olanzapine to 5HT-3 antagonist, NK-1 antagonist, and dexamethasone resulted in significantly more complete responses (CR) and more patients without CINV when compared to placebo in the acute, delayed and overall time periods. Data with olanzapine as CINV prophylaxis is not clear in HCT patients, but one retrospective study by Trifilio et. al. illustrates possible benefit in HCT. They compared an aprepitant-based regimen (aprepitant, ondansetron, and steroid) to an olanzapine-based regimen (olanzapine, ondansetron, and steroid) and found that patients in the olanzapine group had significantly less acute and delayed nausea. In addition, the olanzapine-based regimen required significantly less PRN rescue medication compared to the aprepitant based regimen. These results ultimately provided the foundation for the FOND-O study, a prospective trial that added olanzapine as part of CINV prophylaxis in both hematologic malignancies and HCT patients. The FOND-O study compared fosaprepitant, ondansetron, and dexamethasone (FOND) to fosaprepitant, ondansetron, dexamethasone and olanzapine (FOND-O). The inclusion of olanzapine resulted in significantly less delayed and overall nausea but did not affect the acute phase. While the FOND-O study was the first to look at utilizing olanzapine as part of 4 drug CINV prophylaxis in HCT, there were only 68 HCT patients included in the study. Only 24 allogeneic transplants and 44 autologous transplants were enrolled, and only 34 of these patients actually received olanzapine.
In addition, the FOND-O study utilized an olanzapine dose of 10 mg on each day of chemotherapy continued through chemotherapy day 3. Rationale for Clinical Study The purpose of our proposed study is to build upon the FOND-O results by doing a prospective, randomized, placebo-controlled study, focused entirely on HCT recipients, and powered to detect olanzapine's potential role in CINV prophylaxis in recipients of HCT. Based upon the available literature in both solid and hematologic malignancies the benefit outweighs the risk of adding olanzapine to standard CINV prophylaxis. The primary endpoint is complete response- defined as no emesis and no more than minimal nausea starting with the first dose of highly or moderately emetogenic conditioning chemotherapy and continuing 5 days beyond the last dose of highly or moderately emetogenic conditioning chemotherapy. Secondary endpoints are defined explicitly
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Being tested
- Olanzapine 5 MG, Placebo
- Keywords
- Chemotherapy-induced Nausea and Vomiting, Chemotherapy, Nausea and Vomiting, Olanzapine
- Medical subject headings
- Vomiting, Nausea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olanzapine 5 MGDrug
Also called Zyprexa
It will be a de-identified pill created by investigational drug services at University of North Carolina
PlaceboDrug
It will be a de-identified pill created by investigational drug services at University of North Carolina
| Study group | Role | What they receive |
|---|---|---|
| Olanzapine Arm | Experimental | Olanzapine 5mg tablet with chemotherapy, and 3 days after Receives: Drug: Olanzapine 5 MG |
| Placebo Arm | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: 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
The total number of rescue medications needed acute was calculated, starting from the first dose of highly or moderately emetogenic conditioning chemotherapy and continuing for one day after the last dose of highly or moderately emetogenic conditioning chemotherapy.
The rescue medication is defined as documented administration of an anti-emetic agent other than those that are scheduled for chemotherapy-induced nausea and vomiting (CINV) prophylaxis.
Measured: End of day 1 following last chemotherapy administration. (Up to day 2)
Number of Subjects Achieving Minimal Nausea
To determine the number of subjects achieving minimal nausea was defined as the frequency of participants responded to the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) nausea question "In the last 24 hours, how often did you have nausea?" as "rarely or less" Starting with the first dose of chemotherapy and continuing for one day after the last dose of highly or moderately emetogenic conditioning chemotherapy.
PRO-CTCAE of nausea scale includes categories: Never, Rarely, Occasionally, Frequently, Almost constantly To meet this endpoint the score reported for the Pro-CTCAE question for nausea frequency cannot exceed "rarely" and the score reported for the Pro-CTCAE question for nausea severity cannot exceed "mild"
Measured: Day 2-12
Frequency of Nausea in the Acute Phase
Starting with the first dose of highly or moderately emetogenic conditioning chemotherapy and continuing for one day after the last dose of highly or moderately emetogenic conditioning chemotherapy.
Nausea was assessed using subjects' responses to the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) nausea questions. Scale: Never, Rarely, Occasionally, Frequently, Almost constantly.
To meet this endpoint the score reported for the Pro-CTCAE question for nausea frequency cannot exceed "rarely" in the first 24 hours following receipt of chemotherapy.
Measured: End of day 1 following last chemotherapy administration (Up to day 2)
Number of Subjects Achieved Emesis Endpoint in Acute Phase.
: The number of subjects who did not experience emesis, starting from the first dose of highly or moderately emetogenic conditioning chemotherapy and continuing for one day after the last dose of highly or moderately emetogenic conditioning chemotherapy. Met endpoint = 0 emesis.
Measured: End of day 1 following last chemotherapy administration. (Up to day 2)
Frequency of Somnolence
The frequency of somnolence was determined as the number of patients who experienced somnolence based on Common Terminology Criteria for Adverse Events version 5 (CTCAE v5). The number of subjects has somnolence during the study period was counted.
Measured: Day 2-12
Safety Endpoint: Qtc Prolongation
Prolongation of corrected QTc interval graded as defined in Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Corrected QTc was calculated using Fredericia's Formula. Corrected QT interval (QTc) = QT interval / (60/Heart rate)^0.33.
Measured: Day 1 to 5 days after end of the chemotherapy (Days 2- 12).
Number of Subjects Achieved Nausea Endpoint in the Delayed Phase.
Nausea was assessed using subjects' responses to the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) nausea questions, starting the second day after the completion of highly or moderately emetogenic conditioning chemotherapy and continuing through the fifth day after the completion of highly or moderately emetogenic chemotherapy.
Scale: Never, Rarely, Occasionally, Frequently, Almost constantly.
The number of subjects who experienced "never" or "rarely" nausea were considered as met the endpoint while those who experienced "occasionally", "frequently" or "almost constantly" were considered as not met the endpoint.
Measured: Day 1 to 5 days after end of the chemotherapy (Days 2-12).
Severity of Nausea in Delayed Phase
The severity of nausea in the delayed phase was defined as the response of the subject to the PRO- CTCAE nausea question.
Starting the second day after the completion of highly or moderately emetogenic conditioning chemotherapy and continuing through the fifth day after the completion of highly or moderately emetogenic chemotherapy (PRO-CTCAE) Scale: Never, Rarely, Occasionally, Frequently, Almost constantly
- meet the endpoint, the subject could not have answered a score as higher than "mild" in the period of time starting 24 hours after the last dose of chemotherapy and continuing until the 5th day following receipt of chemotherapy .
Measured: Day 2-12
Number of Emesis Episodes in Delayed Phase
The number of emesis episodes in acute phase was defined as the number of subjects with no emesis, 1 emesis, and 2 or more emesis.
Measured: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Total Number of Rescue Medications Needed -Delayed
The total number of rescue medications needed for breakthrough chemotherapy-induced nausea and vomiting were calculated, starting from the second day after the completion of highly or moderately emetogenic conditioning chemotherapy and continuing through the fifth day after the completion of highly or moderately emetogenic chemotherapy.
The rescue medication is defined as documented administration of an anti-emetic agent other than those that are scheduled for CINV prophylaxis.
Measured: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start18 Aug 2020
- Primary completion11 Apr 2022
- Study completion11 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy-induced Nausea and VomitingStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of North Carolina, Chapel Hill
- Responsible party
- Sponsor
- Investigators
- Jonathan Ptachcinski, PharmD, Principal investigator, jonathan.Ptachcinski@unchealth.unc.edu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04535141
- Sponsor's protocol ID
- LCCC2037
- Other IDs
- 20-0833
- Status last verified
- May 2023
- First submitted
- 18 Aug 2020
- Last updated
- 9 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31635549Navari 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.
PubMed 27410922Hesketh 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.
PubMed 28759346Trifilio 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.
PubMed 28694084Navari 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.
PubMed 27050207Clemmons 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.
PubMed 29906570Basch 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.
PubMed 30204536
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Olanzapine to Standard CINV Prophylaxis in Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT04535141
- Acronym / sponsor ID
- LCCC2037
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Keywords
- Chemotherapy-induced Nausea and Vomiting, Chemotherapy, Nausea and Vomiting, Olanzapine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- University of North Carolina, Chapel Hill
- Study start
- 18 Aug 2020 (actual)
- Primary completion
- 11 Apr 2022 (actual)
- Study completion
- 11 Apr 2022 (actual)
- First posted
- 1 Sep 2020 (actual)
- Results
- Posted 9 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Chemotherapy induced nausea and vomiting (CINV) occurs in up to 80% of patients on active therapy and remains a significant barrier to quality of life. CINV can alter electrolytes and enteral nutrition which can have a detrimental effect on patient adherence and health outcomes. Hematopoietic Stem Cell Transplant (HCT) patients are at increased risk for CINV because many of the conditioning regimens require multiple days of high-dose chemotherapy that are, in many cases, associated with highly-emetogenic potential.
Thus, most conditioning regimens require a 3-drug regimen for optimal CINV prophylaxis.
Current Standard of Care Current guidelines support the use of olanzapine in addition to a 3 drug CINV regimen for highly emetogenic chemotherapy, however some controversy remains as to olanzapine's place in therapy with moderately emetogenic chemotherapy. In HCT, current practice at University of North Carolina utilizes an neurokinin-1 receptor antagonist (NK1 RA), serotonin receptor antagonists (5-HT3 RA) and corticosteroid for CINV prophylaxis in conditioning regimens including moderate and highly emetogenic chemotherapy in accordance with American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommendations.
Olanzapine, an atypical antipsychotic, antagonizes dopamine, serotonin, catecholamines, acetylcholine, and histamine receptors which helps prevent acute, breakthrough and delayed nausea. Olanzapine has shown benefit when used as prophylaxis in solid tumor patients receiving single-day highly emetogenic chemotherapy. The addition of olanzapine to 5HT-3 antagonist, NK-1 antagonist, and dexamethasone resulted in significantly more complete responses (CR) and more patients without CINV when compared to placebo in the acute, delayed and overall time periods. Data with olanzapine as CINV prophylaxis is not clear in HCT patients, but one retrospective study by Trifilio et. al. illustrates possible benefit in HCT. They compared an aprepitant-based regimen (aprepitant, ondansetron, and steroid) to an olanzapine-based regimen (olanzapine, ondansetron, and steroid) and found that patients in the olanzapine group had significantly less acute and delayed nausea. In addition, the olanzapine-based regimen required significantly less PRN rescue medication compared to the aprepitant based regimen. These results ultimately provided the foundation for the FOND-O study, a prospective trial that added olanzapine as part of CINV prophylaxis in both hematologic malignancies and HCT patients. The FOND-O study compared fosaprepitant, ondansetron, and dexamethasone (FOND) to fosaprepitant, ondansetron, dexamethasone and olanzapine (FOND-O). The inclusion of olanzapine resulted in significantly less delayed and overall nausea but did not affect the acute phase. While the FOND-O study was the first to look at utilizing olanzapine as part of 4 drug CINV prophylaxis in HCT, there were only 68 HCT patients included in the study. Only 24 allogeneic transplants and 44 autologous transplants were enrolled, and only 34 of these patients actually received olanzapine.
In addition, the FOND-O study utilized an olanzapine dose of 10 mg on each day of chemotherapy continued through chemotherapy day 3. Rationale for Clinical Study The purpose of our proposed study is to build upon the FOND-O results by doing a prospective, randomized, placebo-controlled study, focused entirely on HCT recipients, and powered to detect olanzapine's potential role in CINV prophylaxis in recipients of HCT. Based upon the available literature in both solid and hematologic malignancies the benefit outweighs the risk of adding olanzapine to standard CINV prophylaxis. The primary endpoint is complete response- defined as no emesis and no more than minimal nausea starting with the first dose of highly or moderately emetogenic conditioning chemotherapy and continuing 5 days beyond the last dose of highly or moderately emetogenic conditioning chemotherapy. Secondary endpoints are defined explicitly
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olanzapine Arm | Experimental | Drug: Olanzapine 5 MGOlanzapine 5mg tablet with chemotherapy, and 3 days after |
| Placebo Arm | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olanzapine 5 MGAlso: ZyprexaIt will be a de-identified pill created by investigational drug services at University of North Carolina | Drug | Olanzapine Arm |
| PlaceboIt will be a de-identified pill created by investigational drug services at University of North Carolina | Drug | Placebo Arm |
Primary outcome
Number of Participants With Complete Response
Time frame: End of study assessment period, until 5 days after last chemotherapy administration (2- 12 days)
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".
10 secondary outcomes
Total Number of Rescue Medications Needed Acute
Time frame: End of day 1 following last chemotherapy administration. (Up to day 2)
Number of Subjects Achieving Minimal Nausea
Time frame: Day 2-12
Frequency of Nausea in the Acute Phase
Time frame: End of day 1 following last chemotherapy administration (Up to day 2)
Number of Subjects Achieved Emesis Endpoint in Acute Phase.
Time frame: End of day 1 following last chemotherapy administration. (Up to day 2)
Frequency of Somnolence
Time frame: Day 2-12
Safety Endpoint: Qtc Prolongation
Time frame: Day 1 to 5 days after end of the chemotherapy (Days 2- 12).
Number of Subjects Achieved Nausea Endpoint in the Delayed Phase.
Time frame: Day 1 to 5 days after end of the chemotherapy (Days 2-12).
Severity of Nausea in Delayed Phase
Time frame: Day 2-12
Number of Emesis Episodes in Delayed Phase
Time frame: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Total Number of Rescue Medications Needed -Delayed
Time frame: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31635549Monson 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.
- Background: PubMed 27410922Navari 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.
- Background: PubMed 28759346Hesketh 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.
- Background: PubMed 28694084Trifilio 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.
- Background: PubMed 27050207Navari 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.
- Background: PubMed 29906570Clemmons 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.
- Background: PubMed 30204536Basch 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Ptachcinski, PharmD principal investigator
jonathan.Ptachcinski@unchealth.unc.edu
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olanzapine 5 MG in people with Chemotherapy-induced Nausea and Vomiting, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Response (time frame: End of study assessment period, until 5 days after last chemotherapy administration (2- 12 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04535141, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.