Nausea, Vomiting
Conditions
Keywords
autologous, myeloma, transplant
Brief summary
The purpose of this study is to help answer the following research question: * Whether administration of an aprepitant containing regimen, an olanzapine containing regimen or regimen containing both will prevent nausea and vomiting better for patients undergoing an autologous stem cell transplant with melphalan chemotherapy. Both of these medications are approved by the United States Food and Drug Administration (FDA) for nausea and vomiting. * Participants will be randomly assigned to one of the 3 treatment groups: * Arm A: aprepitant containing anti-emetic therapy * Arm B: olanzapine containing anti-emetic therapy * Arm C: Aprepitant plus olanzapine containing anti-emetic therapy
Detailed description
This is a multi-center, randomized, non-inferiority phase 3 study conducted to determine an appropriate anti-emetic regimen for patients receiving melphalan for an autologous stem cell transplant (SCT). Candidates for this trial will include patients aged 18-80 years with hematologic malignancies receiving high dose melphalan as part of a conditioning regimen for an autologous stem cell transplant. Patients will be enrolled in 3 arms. Patients in Arm A will receive an aprepitant containing anti-emetic regimen. Patients in Arm B will receive an olanzapine containing anti-emetic regimen. Patients in Arm C will receive an aprepitant plus olanzapine containing anti-emetic regimen. Patients must be able to tolerate oral medications. Patients will be carefully monitored for rates of emesis, nausea, and mucositis. Any adverse events will be recorded. Impact on quality of life will also be assessed. A total of 184 patients will be accrued to each arm. It is anticipated that the accrual period will last approximately 2-3 years. The primary endpoint of this study is a complete response, defined as no emesis and no rescue therapy within 120 hours of melphalan administration.
Interventions
DRUGo Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1
Add aprepitant to anti-emetic regimen
DRUGOlanzapine10 mg orally daily on Days -1,0,+1 and +2
add olanzapine to anti-emetic regimen
DRUGAprepitant plus Olanzapine
add aprepitant and olanzapine to anti-emetic regimen
Sponsors
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Autologous transplant containing high dose melphalan as part of the conditioning regimen (single or 2 day melphalan; BEAM \[carmustine, etoposide, cytarabine, melphalan\]) * able to tolerate oral medications
Exclusion criteria
* Nausea/vomiting within 12 hours before planned high dose conditioning chemotherapy * Any anti-emetic treatment within 24 hours before planned high dose conditioning chemotherapy * Pregnancy * Baseline corrected QT interval (QTc) \> 500 ms * History of seizures * History of central nervous system (CNS) disease * Human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) | within 120 hours following melphalan administration; no emesis and no rescue therapy within 120 hours of melphalan administration (within 120 hours following last day of melphalan administration at baseline) | no emesis and no rescue anti-emetic therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Complete Response | 0 (transplant time) to 24 hours post-transplant | no emesis or rescue therapy; Acute complete response defined as no emesis or rescue therapy required from time point of 0 to 24 hours following melphalan therapy administration |
| Delayed Complete Response | 25-120 hours post-transplant | no emesis or rescue therapy administered; Delayed complete response defined as no emesis or rescue therapy required from time point of 25 hours to 120 hours following melphalan therapy administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant aprepitant plus standard anti-emetic regimen
Aprepitant: Add aprepitant to anti-emetic regimen | 14 |
| Olanzapine olanzapine plus standard anti-emetic regimen
Olanzapine: add olanzapine to anti-emetic regimen | 21 |
| Aprepitant Plus Olanzapine aprepitant and olanzapine plus standard anti-emetic regimen
Aprepitant plus Olanzapine: add aprepitant and olanzapine to anti-emetic regimen | 8 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not complete survey | 2 | 2 | 0 |
| Overall Study | met exclusion criteria | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Aprepitant | Olanzapine | Aprepitant Plus Olanzapine | Total |
|---|---|---|---|---|
| Age, Continuous | 58.5 years | 61 years | 54 years | 57.5 years |
| Conditioning Chemotherapy Regimen 1-day melphalan | 11 participants | 14 participants | 6 participants | 31 participants |
| Conditioning Chemotherapy Regimen 2-day melphalan | 0 participants | 1 participants | 0 participants | 1 participants |
| Conditioning Chemotherapy Regimen BEAM | 3 participants | 6 participants | 2 participants | 11 participants |
| Race/Ethnicity, Customized African American | 5 participants | 5 participants | 4 participants | 14 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian/White | 6 participants | 15 participants | 3 participants | 24 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 14 participants | 21 participants | 8 participants | 43 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 6 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 21 / 21 | 0 / 8 |
| other Total, other adverse events | 0 / 14 | 0 / 21 | 0 / 8 |
| serious Total, serious adverse events | 3 / 14 | 3 / 21 | 1 / 8 |
Outcome results
Primary
Complete Response (CR)
no emesis and no rescue anti-emetic therapy
Time frame: within 120 hours following melphalan administration; no emesis and no rescue therapy within 120 hours of melphalan administration (within 120 hours following last day of melphalan administration at baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aprepitant | Complete Response (CR) | 4 Participants |
| Olanzapine | Complete Response (CR) | 11 Participants |
| Aprepitant Plus Olanzapine | Complete Response (CR) | 4 Participants |
Secondary
Acute Complete Response
no emesis or rescue therapy; Acute complete response defined as no emesis or rescue therapy required from time point of 0 to 24 hours following melphalan therapy administration
Time frame: 0 (transplant time) to 24 hours post-transplant
Population: No data were collected or analyzed for this outcome.
Secondary
Delayed Complete Response
no emesis or rescue therapy administered; Delayed complete response defined as no emesis or rescue therapy required from time point of 25 hours to 120 hours following melphalan therapy administration
Time frame: 25-120 hours post-transplant
Population: No data were collected or analyzed for this outcome.