Combined Use of Multi-Day Doses of Palonosetron and Aprepitant With Low Doses Dexamethasone in Prevention of Nausea and Emesis Among Patients With Multiple Myeloma and Lymphoma Undergoing Autologous Stem Cell Transplant: A Pilot Study
18 Years
N/A
Both
Myeloma, Plasma-Cell, Lymphoma, Malignant
Trial Information
Combined Use of Multi-Day Doses of Palonosetron and Aprepitant With Low Doses Dexamethasone in Prevention of Nausea and Emesis Among Patients With Multiple Myeloma and Lymphoma Undergoing Autologous Stem Cell Transplant: A Pilot Study
The use of high doses of chemotherapy and autologous stem cell transplant has been shown to
prolong disease control among patients with multiple myeloma and patients with lymphomas
that have relapsed or recurred. Patients who receive autologous stem cell transplants have
their own stem cells collected and stored prior to receiving high-dose chemotherapy, the
stem cells are then given back to the patient as a transplant. However, the use of high
doses of chemotherapy is associated with significant side effects of nausea and vomiting.
Before the use of newer medications, the incidence of nausea and vomiting could be as high
as 70-90%.
Nausea is an unpleasant feeling and awareness of the urge to vomit. Vomiting is the process
of throwing up forcefully the contents of the stomach. Retching is an act similar to
vomiting but do not produce throwing up of the contents of the stomach. It is also called
"dry heaves".
There are three kinds of nausea and vomiting associated with chemotherapy. Acute nausea
and/or vomiting occur within the first 24 hours after administration of chemotherapy.
Delayed nausea and/or vomiting begins after the first 24 hours of chemotherapy and could
last for several days afterwards. Anticipatory nausea/vomiting is experienced prior to
administration of the subsequent chemotherapy.
Chemotherapy produces nausea and vomiting by damaging the cells lining the stomach and
intestines which results in the release a substance called serotonin. The serotonin binds
to a protein or "receptor" (5-HT3 receptor) in the lining of the intestines. The receptors
then send a message to the vomiting center in the brain. The brain then sends signals to
the body to produce nausea and vomiting.
Another substance, called substance P, is also released from the lining of the stomach and
intestines with damage by chemotherapy, and is released together with serotonin. The
substance P binds to another protein called "neurokinin-1 receptor" or NK-1 receptor. These
proteins are found in the intestines and another portion of the brain called "tractus
solitarius". The brain then signals the body to produce nausea and vomiting.
The stimulation of the serotonin proteins results in acute nausea and vomiting. The
stimulation of the NK-1 protein results in delayed nausea and vomiting.
There are medications that could block the serotonin and NK-1 proteins. Serotonin blockers
such as ondansetron or Zofran® are now considered the medications of choice to prevent and
treat nausea and vomiting in the transplant setting. However, their use could still result
in nausea and vomiting in up to 40-50% of patients.
Nausea and vomiting negatively impacts the quality of life of patients undergoing stem cell
transplant for their multiple myeloma and lymphoma. It can affect their appetite and sleep;
and can interfere with activity, social life and enjoyment of life. Therefore, it is
important to find better ways to prevent and control nausea and vomiting associated with
chemotherapy.
There are two new medications that are available for patients who receive regular doses of
chemotherapy. One is the long acting preparation of the serotonin blocker called
palonosetron or Aloxi®. It is used to control both acute and delayed nausea and vomiting.
Another medication could block the NK-1 receptor, and is called aprepitant or Emend®. This
prevents delayed nausea and vomiting.
Although these two medications are tested and proven to be effective among patients who
receive regular doses of chemotherapy, they have not been tested in combination among
patients who undergo high doses of chemotherapy in the setting of autologous stem cell
transplant.
The purpose of this study is to evaluate if the combination of these two medications,
together with small doses of steroids (dexamethasone), would be effective in preventing both
acute and delayed vomiting associated with high doses of chemotherapy and stem cell
transplant for patients with multiple myeloma and lymphoma. The usual way to administer
palonosetron is by single injection in the vein before chemotherapy. This is shown to be
effective for chemotherapy given for 1 day. Since chemotherapy regimen for transplant
requires multiple days of treatment, palonosetron will also be administered on multiple days
thereby delivering higher doses of this drug. Aprepitant would be administered at standard
doses. This study would assess if combining palonosetron and aprepitant as well as giving
multiple and higher doses of palonosetron would be safe and effective in the control of
nausea and vomiting in the setting of transplant. The study would evaluate the effect of
combined palonosetron and aprepitant on the quality of life with regards to nausea and
vomiting, of patients undergoing transplant.
Inclusion Criteria:
1. Patients with multiple myeloma and lymphoma deemed by the treating institution to be
candidates for high dose chemotherapy and autologous hematopoietic stem cell
transplant.
2. Both males and females are eligible.
3. Patients should be 18 years old; multiple myeloma patients up to age 75 and lymphoma
patients up to age 65 are eligible.
4. Patients with Karnofsky performance status of 60% or better.
5. Patients should have at least 2.5 x 106 cyropreserved CD34+ cells per kilogram
available for transplantation.
6. Patients with adequate bone marrow function as defined as ANC ≥1000 cells/mm3 ,
platelet ≥ 75,000 cells/mm3.
7. Lymphoma patient must have adequate renal function as defined by a calculated
creatinine clearance of 50% measured in ml/min.
8. The criteria for renal function does not apply for multiple myeloma patients.
Multiple myeloma patients undergoing hemodialysis are eligible.
9. All patients must have a MUGA scan indicating a left ventricular ejection fraction
(LVEF) of greater or equal to 48% within 42 days prior to registration.
10. Patients must have adequate pulmonary function as defined by room air pulse oximetry
equal to or greater than 93%, and pulmonary function tests (FEV1 and DLCO) equal to
or greater than 50% of predicted values.
11. Patients with adequate hepatic function as defined by serum bilirubin lower than 2.5
mg/dL and liver function tests to not exceed greater than 1.5x of the institutions
ULN.
12. All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with the institutional and
federal guidelines.
13. Patients must be able to complete the anti-emesis assessment questionnaire. A
Spanish questionnaire will be available for Hispanic-speaking patients.
Exclusion Criteria:
1. Patients with nausea and have emetic episodes, and are receiving any anti-emetic
medication taken within 24 hours of receiving antibiotics.
2. Active infection involving intravenous antibiotics.
3. Patients with known active hepatitis B and/or hepatitis C infections are excluded.
4. Patients with known HIV infection.
5. Primary or secondary brain neoplasms with increased intracranial pressure.
6. Received intrathecal chemotherapy within 24 hours of first dose of conditioning
chemotherapy.
7. Patients who are nursing mothers or pregnant. Females of childbearing age are
required to have a negative serum B-HCG pregnancy test 24 hours prior to enrollment
on the study.
8. Patients with previous malignancies at other sites except surgically treated
nonmelanomatous skin cancers, prostate cancer or superficial cervical cancers, or
other cancer from which the patient had been disease free for 5 or more years.
9. Patients with uncontrolled medical problems such as diabetes mellitus, cardiac (i.e.
congestive heart failure, coronary heart disease, arrhythmias), pulmonary hepatic and
renal disease unless renal insufficiency is felt to be secondary to multiple
myeloma,
10. Myocardial infarction within 6 months of enrollment in the study.
11. Major surgery within 4 weeks of enrollment.
12. Morbid obesity (BMI>40)
13. Patients with psychiatric or central nervous systems disorders interfering with
ability to comply with study protocol.
14. Patients receiving therapeutic anticoagulant therapy for venous thromboembolic
episode or other hypercoaguable states. Coumadin at 1 mg as prophylaxis for central
venous catheter is allowed.
15. Known hypersensitivity to 5-HT3 antagonists and Aprepitant and their components.
16. Use of non-prescription and herbal-type medications within 72 hours of enrollment on
the study. Their use are not allowed during the study. Multivitamins, nutritional
supplements such as Boost, and other electrolyte replacements are allowed.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
To determine the efficacy and assess the antiemetic response of the combination of Aprepitant and Palonosetron with Prochlorperazine, Lorazepam and low doses of Dexamethasone in achieving complete control from vomiting and nausea among hematopoietic stem
Outcome Time Frame:
24 hours, Day 3, Day 7
Safety Issue:
Yes
Principal Investigator
Omar Aljitawi, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Kansas
Authority:
United States: Institutional Review Board
Study ID:
10862
NCT ID:
NCT00600353
Start Date:
October 2007
Completion Date:
January 2010
Related Keywords:
- Myeloma, Plasma-Cell
- Lymphoma, Malignant
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
