Chemotherapy-induced Nausea and Vomiting
Conditions
Keywords
Chemotherapy-induced Nausea and Vomiting, Chemotherapy, Nausea and Vomiting, Olanzapine
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.
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
Interventions
DRUGOlanzapine 5 MG
It will be a de-identified pill created by investigational drug services at University of North Carolina
DRUGPlacebo
It will be a de-identified pill created by investigational drug services at University of North Carolina
Sponsors
University of North Carolina, Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. 2. Recipients receiving autologous or allogeneic HCT for any disease 3. Any conditioning chemotherapy regimen considered a standard bone marrow transplantation conditioning regimen 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 5. The subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.
Exclusion criteria
1. Patients must not have started conditioning chemotherapy prior to consent. Note: test dose Busulfan is not part of conditioning chemotherapy 2. Known allergy to olanzapine 3. Baseline corrected QT interval ( QTc )\>500 msec as calculated by the Fridericia formula 4. Patients receiving post-transplant cyclophosphamide as planned graft-versus-host disease (GVHD) prophylaxis 5. Pregnant or breastfeeding (NOTE: patients pregnant or breast-feeding are not eligible to proceed to transplant). 6. 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. 7. Treatment with any investigational drug within 7 days prior to registration. 8. Subject is receiving prohibited medications (ciprofloxacin or fluvoxamine) that cannot be discontinued/replaced by an alternative therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Minimal Nausea | Day 2-12 | 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 |
| Frequency of Nausea in the Acute Phase | End of day 1 following last chemotherapy administration (Up to day 2) | 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. |
| Number of Subjects Achieved Emesis Endpoint in Acute Phase. | End of day 1 following last chemotherapy administration. (Up to day 2) | : 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. |
| Frequency of Somnolence | Day 2-12 | 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. |
| Total Number of Rescue Medications Needed Acute | End of day 1 following last chemotherapy administration. (Up to day 2) | 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. |
| Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. | Day 1 to 5 days after end of the chemotherapy (Days 2-12). | 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. |
| Severity of Nausea in Delayed Phase | Day 2-12 | 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 o 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 . |
| Number of Emesis Episodes in Delayed Phase | Day 1 to 5 days after end of the chemotherapy ( Days 2-12). | 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. |
| Total Number of Rescue Medications Needed -Delayed | Day 1 to 5 days after end of the chemotherapy ( Days 2-12). | 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. |
| Safety Endpoint: Qtc Prolongation | Day 1 to 5 days after end of the chemotherapy (Days 2- 12). | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 08/18/2020 through 03/17/2022 at 1 cancer center in North Carolina.
Pre-assignment details
A total of ninety-four participants consented and three subjects withdrew their consent, and ninety-one enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care All subjects received the usual care and did not receive olanzapine. | 46 |
| Olanzapine All subjects received both olanzapine and usual care. | 45 |
| Total | 91 |
Baseline characteristics
| Characteristic | Usual Care | Olanzapine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 18 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 27 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 40 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 14 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 34 Participants | 25 Participants | 59 Participants |
| Region of Enrollment United States | 46 participants | 45 participants | 91 participants |
| Sex: Female, Male Female | 23 Participants | 17 Participants | 40 Participants |
| Sex: Female, Male Male | 23 Participants | 28 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 45 |
| other Total, other adverse events | 46 / 46 | 45 / 45 |
| serious Total, serious adverse events | 3 / 46 | 8 / 45 |
Outcome results
Primary
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.
Time frame: End of study assessment period, until 5 days after last chemotherapy administration (2- 12 days)
Population: The participants enrolled in the study and complete responses were assessed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Number of Participants With Complete Response | The number of participants achieved a complete response | 13 Participants |
| Usual Care | Number of Participants With Complete Response | The number of participants did not achieve a complete response | 33 Participants |
| Olanzapine | Number of Participants With Complete Response | The number of participants achieved a complete response | 21 Participants |
| Olanzapine | Number of Participants With Complete Response | The number of participants did not achieve a complete response | 24 Participants |
Secondary
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.
Time frame: End of day 1 following last chemotherapy administration (Up to day 2)
Population: The subjects who completed CINV prophylaxis acute phase and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Frequency of Nausea in the Acute Phase | Met endpoint | 43 Participants |
| Usual Care | Frequency of Nausea in the Acute Phase | Did not meet endpoint | 3 Participants |
| Olanzapine | Frequency of Nausea in the Acute Phase | Met endpoint | 44 Participants |
| Olanzapine | Frequency of Nausea in the Acute Phase | Did not meet endpoint | 1 Participants |
Secondary
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.
Time frame: Day 2-12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Frequency of Somnolence | subjects have somnolence | 0 Participants |
| Usual Care | Frequency of Somnolence | subjects do not have somnolence | 46 Participants |
| Olanzapine | Frequency of Somnolence | subjects have somnolence | 1 Participants |
| Olanzapine | Frequency of Somnolence | subjects do not have somnolence | 42 Participants |
Secondary
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.
Time frame: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Population: The subjects who completed the treatment and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Number of Emesis Episodes in Delayed Phase | No emesis episodes | 32 Participants |
| Usual Care | Number of Emesis Episodes in Delayed Phase | 1 emesis episode | 9 Participants |
| Usual Care | Number of Emesis Episodes in Delayed Phase | 2 or more emesis episodes | 5 Participants |
| Olanzapine | Number of Emesis Episodes in Delayed Phase | No emesis episodes | 36 Participants |
| Olanzapine | Number of Emesis Episodes in Delayed Phase | 1 emesis episode | 6 Participants |
| Olanzapine | Number of Emesis Episodes in Delayed Phase | 2 or more emesis episodes | 3 Participants |
Secondary
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.
Time frame: End of day 1 following last chemotherapy administration. (Up to day 2)
Population: The subjects who completed CINV prophylaxis acute phase and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Number of Subjects Achieved Emesis Endpoint in Acute Phase. | Met endpoint | 45 Participants |
| Usual Care | Number of Subjects Achieved Emesis Endpoint in Acute Phase. | Did not meet endpoint | 1 Participants |
| Olanzapine | Number of Subjects Achieved Emesis Endpoint in Acute Phase. | Met endpoint | 45 Participants |
| Olanzapine | Number of Subjects Achieved Emesis Endpoint in Acute Phase. | Did not meet endpoint | 0 Participants |
Secondary
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.
Time frame: Day 1 to 5 days after end of the chemotherapy (Days 2-12).
Population: The subjects who completed the treatment and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. | Met endpoint | 19 Participants |
| Usual Care | Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. | Did not meet endpoint | 27 Participants |
| Olanzapine | Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. | Met endpoint | 27 Participants |
| Olanzapine | Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. | Did not meet endpoint | 18 Participants |
Secondary
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
Time frame: Day 2-12
Population: The subjects who completed CINV prophylaxis treatment and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Number of Subjects Achieving Minimal Nausea | Yes | 15 Participants |
| Usual Care | Number of Subjects Achieving Minimal Nausea | No | 31 Participants |
| Olanzapine | Number of Subjects Achieving Minimal Nausea | Yes | 25 Participants |
| Olanzapine | Number of Subjects Achieving Minimal Nausea | No | 20 Participants |
Secondary
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.
Time frame: Day 1 to 5 days after end of the chemotherapy (Days 2- 12).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Safety Endpoint: Qtc Prolongation | Grade 1 | 3 Participants |
| Usual Care | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Usual Care | Safety Endpoint: Qtc Prolongation | Grade 3 | 0 Participants |
| Usual Care | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Usual Care | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Usual Care | Safety Endpoint: Qtc Prolongation | None | 43 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | None | 41 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | Grade 1 | 4 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | Grade 3 | 0 Participants |
| Olanzapine | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | None | 44 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 3 | 0 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 1 | 2 Participants |
| Usual Care Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 3 | 0 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | None | 42 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Olanzapine Post-chemo Day 1 | Safety Endpoint: Qtc Prolongation | Grade 1 | 3 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | Grade 1 | 3 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | Grade 3 | 1 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Usual Care End of Study | Safety Endpoint: Qtc Prolongation | None | 42 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | Grade 4 | 0 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | Grade 3 | 1 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | Grade 5 | 0 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | None | 41 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | Grade 2 | 0 Participants |
| Olanzapine- End of Study | Safety Endpoint: Qtc Prolongation | Grade 1 | 3 Participants |
Secondary
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 o 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 .
Time frame: Day 2-12
Population: The subjects who completed the treatment and responded to PRO-CTCAE questions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Severity of Nausea in Delayed Phase | Met endpoint | 23 Participants |
| Usual Care | Severity of Nausea in Delayed Phase | Did not meet endpoint | 23 Participants |
| Olanzapine | Severity of Nausea in Delayed Phase | Met endpoint | 31 Participants |
| Olanzapine | Severity of Nausea in Delayed Phase | Did not meet endpoint | 24 Participants |
Secondary
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.
Time frame: End of day 1 following last chemotherapy administration. (Up to day 2)
Population: The subjects who completed CINV prophylaxis treatment and their rescue medications were counted.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Usual Care | Total Number of Rescue Medications Needed Acute | 0.08 number of rescue medication |
| Olanzapine | Total Number of Rescue Medications Needed Acute | 0.10 number of rescue medication |
Secondary
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.
Time frame: Day 1 to 5 days after end of the chemotherapy ( Days 2-12).
Population: The subjects who completed CINV prophylaxis treatment and their rescue medications were counted.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Usual Care | Total Number of Rescue Medications Needed -Delayed | 0.47 number of rescue medication |
| Olanzapine | Total Number of Rescue Medications Needed -Delayed | 1.17 number of rescue medication |