Nausea, Vomiting
Conditions
Keywords
Bone Marrow Transplant, Nausea, Vomiting, NK-1 antagonist
Brief summary
The purpose of this study is to compare two different treatment protocols for treating nausea and vomiting in patients who have undergone bone marrow transplant. Patients will be assigned to one of two treatment groups. The first group will recieve ondansetron (Zofran) tablets combined with a medicine called dexamethasone given IV. Both of these drugs are commercially available. Patients in the second treatment consists of the first two drugs, plus a newly approved drug known as aprepitant (MK-869, Emend). This combination will be the treatment being tested. The combination is approved by the FDA for chemotherapy regimens known to cause a lot of nausea and vomiting. It significantly decreases the delayed (more than 24 hours after therapy) nausea and vomiting seen with these regimens.
Detailed description
This will be a single center, comparative, randomized, double-blind, phase III trial designed to evaluate the efficacy of the NK-1 antagonist, aprepitant (MK-869), in combination with ondansetron and dexamethasone in the prevention of acute and delayed nausea and vomiting compared to ondansetron and dexamethasone in patients receiving highly emetogenic preparative regimens prior to autologous or allogeneic (related and unrelated) stem cell transplantation. Patients will be randomized to one of two treatments: dexamethasone 10 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day vs. 7.5 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day combined with aprepitant, 125 mg orally on the first day of their preparative regimen followed by 80 mg daily on each remaining day of the preparative regimen plus three additional days.
Interventions
DRUGStandard PO (Zofran + Dexamethason)
Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion. A placebo capsule will be given daily on each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.
DRUGAprepitant (MK-869) + Standard PO
Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO \[blinded\] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO \[blinded\] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.
Sponsors
Merck Sharp & Dohme LLC
Loyola University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of cancer, admitted for myelosupppresive stem cell transplantation. Included preparative regimens include: TBI/VP16/CY, TBI/CY, BU/CY (PO & IV), and BCV * Age 18 or older * Alcohol intake \<100 gm/d for the last year (\< approximately 5 drinks per day) * Renal function: estimated or measured CrCl 50 ml/min * Liver function: T.Bili \<1.5, AST \< 2x ULN, unless due to disease * Able to swallow tablets and capsules
Exclusion criteria
* Age \< 18 * High alcohol intake \[\> 100 gm/d in the last year\] * Allergy or intolerance to: ondansetron or dexamethasone * Renal dysfunction \[measured or estimated CrCl \< 50 ml/min\] * Liver dysfunction \[T.Bili \> 1.5, AST \> 2x ULN, unless due to disease\] * Inability to swallow tablets or capsules * Concurrent condition requiring systemic steroid use * Nonmyeloablative SCT, patients receiving the conditioning regimens not included \[see inclusion criteria\] * History of anticipatory nausea and vomiting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rates Among Standard of Care and Combination Therapy Groups. | 14 days | Comparison of complete response (CR) rates between patients receiving ondansetron and dexamethasone and those receiving ondansetron and dexamethasone plus NK-1 antagonist, aprepitant. CR is defined as no emesis and with normal oral intake. Disease response not applicable. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard PO Ondanestron + Dexamethason Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion. A placebo capsule will be given daily on each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen. | 89 |
| Aprepitant (MK-869) + Standard PO Ondanestron + Dexamethason Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO \[blinded\] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO \[blinded\] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen. | 90 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not transplanted. | 0 | 2 |
Baseline characteristics
| Characteristic | Standard PO Ondanestron + Dexamethason | Total | Aprepitant (MK-869) + Standard PO Ondanestron + Dexamethason |
|---|---|---|---|
| Age, Continuous | 51 years | 50 years | 50 years |
| Diagnosis Acute Myelogenous Leukemia | 22 Participants | 46 Participants | 24 Participants |
| Diagnosis Acut Lymphoblastic Lymphoma | 3 Participants | 13 Participants | 10 Participants |
| Diagnosis Chronic Myelogenous Leukemia | 4 Participants | 6 Participants | 2 Participants |
| Diagnosis Hodgkin's lymphoma | 7 Participants | 12 Participants | 5 Participants |
| Diagnosis Multiple Myeloma | 21 Participants | 34 Participants | 13 Participants |
| Diagnosis Non-Hodgkin lymphoma | 28 Participants | 57 Participants | 29 Participants |
| Diagnosis Other | 4 Participants | 11 Participants | 7 Participants |
| Graft Type Autologous-peripheral blood stem cell transplant | 48 Participants | 89 Participants | 41 Participants |
| Graft Type Cord as in umbilical cord | 7 Participants | 13 Participants | 6 Participants |
| Graft Type Matched unrelated donor BMT | 6 Participants | 14 Participants | 8 Participants |
| Graft Type Matched unrelated donor PBPCT | 8 Participants | 20 Participants | 12 Participants |
| Graft Type Related Allo-PBPCT | 19 Participants | 41 Participants | 22 Participants |
| Graft Type Related autologous bone marrow transplant | 1 Participants | 2 Participants | 1 Participants |
| History of prior nausea or vomiting with chemotherapy No | 30 Participants | 55 Participants | 25 Participants |
| History of prior nausea or vomiting with chemotherapy Unknown | 4 Participants | 10 Participants | 6 Participants |
| History of prior nausea or vomiting with chemotherapy Yes | 55 Participants | 114 Participants | 59 Participants |
| History of prior nausea or vomiting with radiation therapy No | 43 Participants | 85 Participants | 42 Participants |
| History of prior nausea or vomiting with radiation therapy Unknown | 4 Participants | 11 Participants | 7 Participants |
| History of prior nausea or vomiting with radiation therapy Yes | 42 Participants | 83 Participants | 41 Participants |
| Preparative Regimen BCV | 11 Participants | 16 Participants | 5 Participants |
| Preparative Regimen I.V. Busulfan/Cy | 7 Participants | 14 Participants | 7 Participants |
| Preparative Regimen Prescribed orally Bu/Cy | 21 Participants | 34 Participants | 13 Participants |
| Preparative Regimen TBI/Etoposide/Cy | 17 Participants | 36 Participants | 19 Participants |
| Preparative Regimen Total body irradiation/Cyclophosphamide | 33 Participants | 79 Participants | 46 Participants |
| Setting Inpatient | 69 Participants | 143 Participants | 74 Participants |
| Setting Outpatient | 20 Participants | 36 Participants | 16 Participants |
| Sex: Female, Male Female | 32 Participants | 65 Participants | 33 Participants |
| Sex: Female, Male Male | 57 Participants | 114 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 89 | 5 / 90 |
| other Total, other adverse events | 52 / 89 | 59 / 90 |
| serious Total, serious adverse events | 2 / 89 | 5 / 90 |
Outcome results
Primary
Complete Response Rates Among Standard of Care and Combination Therapy Groups.
Comparison of complete response (CR) rates between patients receiving ondansetron and dexamethasone and those receiving ondansetron and dexamethasone plus NK-1 antagonist, aprepitant. CR is defined as no emesis and with normal oral intake. Disease response not applicable.
Time frame: 14 days
Population: 179 patients receiving autologous and allogeneic hematopoietic stem cell transplants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard PO Ondanestron + Dexamethason | Complete Response Rates Among Standard of Care and Combination Therapy Groups. | Complete Responder | 58 Participants |
| Standard PO Ondanestron + Dexamethason | Complete Response Rates Among Standard of Care and Combination Therapy Groups. | Not Complete Responder | 31 Participants |
| Aprepitant (MK-869) + Standard PO Ondanestron + Dexamethason | Complete Response Rates Among Standard of Care and Combination Therapy Groups. | Complete Responder | 73 Participants |
| Aprepitant (MK-869) + Standard PO Ondanestron + Dexamethason | Complete Response Rates Among Standard of Care and Combination Therapy Groups. | Not Complete Responder | 17 Participants |
Comparison: The null hypothesis is that there will be a higher proportion of complete responders among those subjects receiving the combination therapy.p-value: <0.001Chi-squared