Trial Outcomes & Findings for Olanzapine for Nausea/Vomiting Prophylaxis in Recipients of Hematopoietic Stem Cell Transplants (NCT NCT04535141)

Last Updated: 2023-05-09

Results Overview

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".

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

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

Results posted on

2023-05-09

Participant Flow

Participants were recruited from 08/18/2020 through 03/17/2022 at 1 cancer center in North Carolina.

A total of ninety-four participants consented and three subjects withdrew their consent, and ninety-one enrolled in the study.

Participant milestones

Participant milestones
Measure	Usual Care All subjects received the usual care and did not receive olanzapine.	Olanzapine All subjects received both olanzapine and usual care.
Overall Study STARTED	46	45
Overall Study COMPLETED	46	45
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Total n=91 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=99 Participants	27 Participants n=107 Participants	56 Participants n=206 Participants
Age, Categorical >=65 years	17 Participants n=99 Participants	18 Participants n=107 Participants	35 Participants n=206 Participants
Sex: Female, Male Female	23 Participants n=99 Participants	17 Participants n=107 Participants	40 Participants n=206 Participants
Sex: Female, Male Male	23 Participants n=99 Participants	28 Participants n=107 Participants	51 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=99 Participants	40 Participants n=107 Participants	82 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	8 Participants n=99 Participants	14 Participants n=107 Participants	22 Participants n=206 Participants
Race (NIH/OMB) White	34 Participants n=99 Participants	25 Participants n=107 Participants	59 Participants n=206 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Region of Enrollment United States	46 participants n=99 Participants	45 participants n=107 Participants	91 participants n=206 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Number of Participants With Complete Response The number of participants achieved a complete response	13 Participants	21 Participants	—	—	—	—
Number of Participants With Complete Response The number of participants did not achieve a complete response	33 Participants	24 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Total Number of Rescue Medications Needed Acute	0.08 number of rescue medication Interval 0.0 to 2.0	0.10 number of rescue medication Interval 0.0 to 2.0	—	—	—	—

SECONDARY outcome

Timeframe: Day 2-12

Population: The subjects who completed CINV prophylaxis treatment and responded to PRO-CTCAE questions.

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"

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Number of Subjects Achieving Minimal Nausea Yes	15 Participants	25 Participants	—	—	—	—
Number of Subjects Achieving Minimal Nausea No	31 Participants	20 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Frequency of Nausea in the Acute Phase Met endpoint	43 Participants	44 Participants	—	—	—	—
Frequency of Nausea in the Acute Phase Did not meet endpoint	3 Participants	1 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

: 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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Number of Subjects Achieved Emesis Endpoint in Acute Phase. Met endpoint	45 Participants	45 Participants	—	—	—	—
Number of Subjects Achieved Emesis Endpoint in Acute Phase. Did not meet endpoint	1 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=43 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Frequency of Somnolence subjects have somnolence	0 Participants	1 Participants	—	—	—	—
Frequency of Somnolence subjects do not have somnolence	46 Participants	42 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 n=46 Participants All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 n=45 Participants All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study n=46 Participants All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study n=45 Participants All subjects received both olanzapine and usual care. EKG was performed at end of study
Safety Endpoint: Qtc Prolongation Grade 1	3 Participants	4 Participants	2 Participants	3 Participants	3 Participants	3 Participants
Safety Endpoint: Qtc Prolongation Grade 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Endpoint: Qtc Prolongation Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Safety Endpoint: Qtc Prolongation Grade 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Endpoint: Qtc Prolongation Grade 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Endpoint: Qtc Prolongation None	43 Participants	41 Participants	44 Participants	42 Participants	42 Participants	41 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. Met endpoint	19 Participants	27 Participants	—	—	—	—
Number of Subjects Achieved Nausea Endpoint in the Delayed Phase. Did not meet endpoint	27 Participants	18 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Day 2-12

Population: The subjects who completed the treatment and responded to PRO-CTCAE questions.

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 .

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Severity of Nausea in Delayed Phase Met endpoint	23 Participants	31 Participants	—	—	—	—
Severity of Nausea in Delayed Phase Did not meet endpoint	23 Participants	24 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Number of Emesis Episodes in Delayed Phase No emesis episodes	32 Participants	36 Participants	—	—	—	—
Number of Emesis Episodes in Delayed Phase 1 emesis episode	9 Participants	6 Participants	—	—	—	—
Number of Emesis Episodes in Delayed Phase 2 or more emesis episodes	5 Participants	3 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Usual Care n=46 Participants All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 Participants All subjects received both olanzapine and usual care.	Usual Care Post-chemo Day 1 All subjects received the usual care and did not receive olanzapine. EKG was performed on post-chemo day 1	Olanzapine Post-chemo Day 1 All subjects received both olanzapine and usual care. EKG was performed at post-chemo day 1	Usual Care End of Study All subjects received the usual care and did not receive olanzapine. EKG was performed at the end of the study	Olanzapine- End of Study All subjects received both olanzapine and usual care. EKG was performed at end of study
Total Number of Rescue Medications Needed -Delayed	0.47 number of rescue medication Interval 0.0 to 44.0	1.17 number of rescue medication Interval 0.0 to 22.0	—	—	—	—

Adverse Events

Usual Care

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Olanzapine

Serious events: 8 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Usual Care n=46 participants at risk All subjects received the usual care and did not receive olanzapine.	Olanzapine n=45 participants at risk All subjects received both olanzapine and usual care.
Cardiac disorders Arrhythmia	4.3% 2/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	0.00% 0/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.
Immune system disorders engraftment syndrome	2.2% 1/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	8.9% 4/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.
Nervous system disorders Encephalopathy	0.00% 0/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	2.2% 1/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.
Immune system disorders cytokine release syndrome	0.00% 0/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	2.2% 1/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.
General disorders Syncopal episode	0.00% 0/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	2.2% 1/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.
Metabolism and nutrition disorders Tumor Lysis Syndrome	0.00% 0/46 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.	2.2% 1/45 • from the first day of the study treatment until end of the treatment (Up to 24 days) Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, from the first day of the study to the end of the treatment.

Other adverse events

Additional Information

Jonathan Ptachcinski PharmD, BCPS, BCOP

University of North Carolina Lineberger Comprehensive Cancer Center

Phone: +1 919-966-9786

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place