Clinical trial NCT00600353
Conditions: Myeloma, Plasma-Cell Lymphoma, Malignant
Keywords: nausea cancer CINV
Sponsor: University of Kansas Medical Center
Start date: 2007-10-01; Completion date: 2010-01-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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).

Detailed description:
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.

Arms: arm 1: Group A: Subjects with Multiple Myeloma

* Conditioning regimen, over a 7 day period, includes:
* Melphalan 70-100 mg, Dexamethasone 4 mg IV push, Aprepitant 125 mg PO, Palonosetron 0.25 mg IV over 30 seconds, Aprepitant 80 mg PO, Dexamethasone 4 mg IV and Lorazepam 1 mg IV x 1 dose 30 minutes prior to stem cell infusion

Group B: Subjects with Lymphoma

* Conditioning regimen, over a 7 day period, includes: (BEAC)
* BCNU 300 mg/m2 IV x 1,Cytarabine 100 mg/m2 IV BID, Etoposide 100 mg/m2 IV BID, administer after, Cyclophosphamide 35 mg/kg QD, Dexamethasone 4 mg IV push, Aprepitant 125 mg PO, Palonosetron 0.25 mg IV over 30 seconds, Aprepitant 80 mg PO, Lorazepam 1 mg IV x 1 dose 30 minutes prior to stem cell transplant
Interventions: intervention 1: Palonosetron intervention 2: Aprepitant intervention 3: Dexamethasone
Intervention descriptions: intervention 1: Palonosetron 0.25 mg IV over 30 seconds intervention 2: Aprepitant 125 mg PO and Aprepitant 80 mg PO intervention 3: Dexamethasone 4 mg IV and Dexamethasone 4 mg IV push

Protocol documents: