Chemotherapy-induced Nausea and Vomiting
Conditions
Keywords
Autologous stem cell transplant, BEAM, Oral busulfan, Cyclophosphamide, Etoposide, Carboplatin, melphalan
Brief summary
In this study, patients will receive ondansetron 8mg and dexamethasone 10mg intravenously 30 minutes prior to myeloablative preparative chemotherapy until the last day of chemotherapy. On the final day of chemotherapy, palonosetron 0.25mg and dexamethasone 10mg will be administered intravenously 30 minutes prior to the chemotherapy. If the chemotherapy regimen is only 1 day of the chemotherapy then only palonosetron and dexamethasone will be administered 30 minutes prior to chemotherapy. Dexamethasone 8mg once daily will be given orally for 2 days following chemotherapy.
Detailed description
In order to decrease this delayed CINV, the investigators have developed a unique schedule of antiemetics that takes advantage of palonosetron's long elimination half-life (40 hours). In this study, patients will receive ondansetron 8mg and dexamethasone 10mg intravenously 30 minutes prior to myeloablative preparative chemotherapy until the last day of chemotherapy. On the final day of chemotherapy, palonosetron 0.25mg and dexamethasone 10mg will be administered intravenously 30 minutes prior to the chemotherapy. If the chemotherapy regimen is only 1 day of the chemotherapy then only palonosetron and dexamethasone will be administered 30 minutes prior to chemotherapy. Dexamethasone 8mg once daily will be given orally for 2 days following chemotherapy. The investigators hypothesize that this antiemetic schedule will significantly reduce the delayed CINV compared to historical controls
Interventions
DRUGPalonosetron
Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV Day 1-2 after IV chemotherapy - Dexamethasone 8 mg PO
DRUGondansetron
Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV
DRUGDexamethasone
Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV
Sponsors
Blood and Marrow Transplant Group of Georgia
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* candidate for high-dose chemotherapy and autologous hematopoietic stem cell transplantation * Karnofsky performance status \>/= 60% * scheduled to receive one of the following conditioning regimens * BEAM * Oral Busulfan/cyclophosphamide with or without etoposide * Carboplatin/Etoposide * Melphalan * Negative pregnancy test * Must be able to complete a daily nausea/vomiting questionnaire and Quality of Life
Exclusion criteria
* Active infection requiring IV antibiotics * Known active hepatitis B and/or hepatitis C or HIV infection * prior non-hematological malignancies at other sites except surgically treated non-melanoma skin cancer, superficial cervical cancer or other cancer from which the patient had been disease free for \>/= 5 years * Uncontrolled medical problems including any of the following * Diabetes mellitus * Cardiac, pulmonary, hepatic or renal disease * myocardial infarction within the past 6 months * Morbid obesity (BMT \>40) * History of CNS metastases, psychiatric or CNS disorders interfering with the ability to comply with the study * Known hypersensitivity to 5-HT3 antagonists, dexamethasone and/or their components * Intrathecal therapy within 24 hours before starting preparative regimen * Receiving any antiemetic therapy 24 hours before starting preparative regimen * Any 5-HT3 antagonist used as a rescue medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate for Delayed Chemotherapy Induced Nausea & Vomiting | 120 hours | Proportion of patients achieving a delayed CINV complete response (CR) defined as no emetic episode and no use of rescue medications during the 24-120 hour period post chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Control Rate for Nausea & Vomiting | 120 hours | Complete control rate (CC; defined as no emetic episodes, no rescue medication use, and no more than mild nausea) |
| Emetic Episodes | 120 Hours | Number of emetic episodes |
| Complete Remission During Acute Phase Post-chemotherapy | 24 hours | Proportion of patients achieving an acute CINV CR during the acute phase post -chemotherapy (0-24 hours) |
| Complete Remission During Overall Chemotherapy Time Period | 120 hours | Proportion of patients achieving a CR during the cumulative overall 0-120 hour time period |
| Number of Patients That Required First Administration of Rescue Medication Within 24 Hours | 24 hours | Number of patients who required the use of rescue medication (lorazepam, prochlorperazine, promethazine, metoclopramide, scopolamine, or dronabinol) within the first 24 hours |
| Number of Patients That Experience Treatment Failure Within the First 24 Hours | 24 hours | Number of patients with first emetic episode or time to administration of rescue therapy, whichever occurred first, within the first 24 hours |
| Patients Who Experience First Emetic Episode Within 24 Hours | 24 hours | Number of patients with first emetic episode experienced within 24 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Palonosetron All patients will receive the following medications prior to and during their high dose chemotherapy for autologous stem cell transplantation
Day x-y of IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV Day z (last day of chemotherapy) - Palonosetron .25 mg IV, dexamethasone 10mg IV Day 1-2 after IV chemotherapy - Dexamethasone 8 mg PO
Palonosetron, ondansetron, dexamethasone: Day x-y of IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV Day z (last day of chemotherapy) - Palonosetron .25 mg IV, dexamethasone 10mg IV Day 1-2 after IV chemotherapy - Dexamethasone 8 mg PO | 85 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | treatment failure | 9 |
Baseline characteristics
| Characteristic | Palonosetron |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 29 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants |
| Age, Continuous | 57 years |
| Region of Enrollment United States | 85 participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 85 / 85 |
| serious Total, serious adverse events | 0 / 85 |
Outcome results
Primary
Complete Response Rate for Delayed Chemotherapy Induced Nausea & Vomiting
Proportion of patients achieving a delayed CINV complete response (CR) defined as no emetic episode and no use of rescue medications during the 24-120 hour period post chemotherapy.
Time frame: 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Complete Response Rate for Delayed Chemotherapy Induced Nausea & Vomiting | 13 participants |
Secondary
Complete Control Rate for Nausea & Vomiting
Complete control rate (CC; defined as no emetic episodes, no rescue medication use, and no more than mild nausea)
Time frame: 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Complete Control Rate for Nausea & Vomiting | 8 participants |
Secondary
Complete Remission During Acute Phase Post-chemotherapy
Proportion of patients achieving an acute CINV CR during the acute phase post -chemotherapy (0-24 hours)
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Complete Remission During Acute Phase Post-chemotherapy | 33 participants |
Secondary
Complete Remission During Overall Chemotherapy Time Period
Proportion of patients achieving a CR during the cumulative overall 0-120 hour time period
Time frame: 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Complete Remission During Overall Chemotherapy Time Period | 10 participants |
Secondary
Emetic Episodes
Number of emetic episodes
Time frame: 120 Hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Palonosetron | Emetic Episodes | 1.7 episodes |
Secondary
Number of Patients That Experience Treatment Failure Within the First 24 Hours
Number of patients with first emetic episode or time to administration of rescue therapy, whichever occurred first, within the first 24 hours
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Number of Patients That Experience Treatment Failure Within the First 24 Hours | 49 participants |
Secondary
Number of Patients That Required First Administration of Rescue Medication Within 24 Hours
Number of patients who required the use of rescue medication (lorazepam, prochlorperazine, promethazine, metoclopramide, scopolamine, or dronabinol) within the first 24 hours
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Number of Patients That Required First Administration of Rescue Medication Within 24 Hours | 46 participants |
Secondary
Patients Who Experience First Emetic Episode Within 24 Hours
Number of patients with first emetic episode experienced within 24 hours
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palonosetron | Patients Who Experience First Emetic Episode Within 24 Hours | 15 participants |