Multi-day Doses in Prevention of Nausea and Emesis
Multi-day Doses in Prevention of Nausea and Emesis
To assess emetic responses to multi-day doses of Palonosetron and Aprepitant and low dose
 dexamethasone +/- Prochlorperazine among patients with multiple myeloma and lymphoma
 undergoing autologous HSCT utilizing the Multinational Association for Supportive Care in
 Cancer (MASCC) Antiemesis Tool (MAT).
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.