Palonosetron, Aprepitant, and Low-Dose Dexamethasone in Preventing Nausea and Vomiting in Patients Undergoing High-Dose Chemotherapy and Stem Cell Transplant for Multiple Myeloma or Lymphoma - Full Text View

Sponsored by:	University of Kansas
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00631930

Purpose

RATIONALE: Giving palonosetron together with aprepitant and low-dose dexamethasone may prevent nausea and vomiting in patients undergoing high-dose chemotherapy and stem cell transplant for multiple myeloma or lymphoma.

PURPOSE: This phase II trial is studying how well giving palonosetron, aprepitant, and low-dose dexamethasone works in preventing nausea and vomiting in patients undergoing high-dose chemotherapy and stem cell transplant for multiple myeloma or lymphoma.

Condition	Intervention	Phase
Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Nausea and Vomiting	Drug: aprepitant Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: etoposide Drug: melphalan Drug: palonosetron hydrochloride Procedure: autologous hematopoietic stem cell transplantation	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Hodgkin's Disease Lymphoma Multiple Myeloma Nausea and Vomiting

Drug Information available for: Cyclophosphamide Cytarabine Cytarabine hydrochloride Etoposide Carmustine Melphalan Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Etoposide phosphate Melphalan hydrochloride Sarcolysin Aprepitant 2-(1-Azabicyclo(2.2.2)oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz(de)isoquinolin-1-one Palonosetron Hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Open Label
Official Title:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Frequency and percent of patients who have complete control, complete emetic response, major emetic response, and minor emetic occurrence [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	October 2007
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 (multiple myeloma): Experimental Patients receive high-dose chemotherapy for multiple myeloma (comprising melphalan IV on days -3 to -2). They also receive dexamethasone IV over 5-10 minutes and oral aprepitant on days -3 to -1 and palonosetron hydrochloride IV over 30 seconds on days -3 and -2 and on day 3. Patients undergo HSCT on day 0.	Drug: aprepitant Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Drug: dexamethasone Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Drug: melphalan Given IV Drug: palonosetron hydrochloride Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Procedure: autologous hematopoietic stem cell transplantation Patients undergo HSCT on day 0
Group 2 (lymphoma): Experimental Patients receive high-dose chemotherapy for lymphoma (comprising carmustine IV once on day -7, cytarabine IV twice daily and etoposide IV twice daily on days -6 to -3, and cyclophosphamide once daily on days -6 to -3). They also receive dexamethasone IV over 5-10 minutes on days -7 to -3, oral aprepitant on days -7 to -5, and palonosetron hydrochloride IV over 30 seconds on days -7 to -3 and on day 3. Patients undergo HSCT on day 0.	Drug: aprepitant Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Drug: carmustine Given IV Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: dexamethasone Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Drug: etoposide Given IV Drug: palonosetron hydrochloride Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally Procedure: autologous hematopoietic stem cell transplantation Patients undergo HSCT on day 0

Arms

Assigned Interventions

Group 1 (multiple myeloma): Experimental

Patients receive high-dose chemotherapy for multiple myeloma (comprising melphalan IV on days -3 to -2). They also receive dexamethasone IV over 5-10 minutes and oral aprepitant on days -3 to -1 and palonosetron hydrochloride IV over 30 seconds on days -3 and -2 and on day 3. Patients undergo HSCT on day 0.

Drug: aprepitant

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Drug: dexamethasone

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Drug: melphalan

Given IV

Drug: palonosetron hydrochloride

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Procedure: autologous hematopoietic stem cell transplantation

Patients undergo HSCT on day 0

Group 2 (lymphoma): Experimental

Patients receive high-dose chemotherapy for lymphoma (comprising carmustine IV once on day -7, cytarabine IV twice daily and etoposide IV twice daily on days -6 to -3, and cyclophosphamide once daily on days -6 to -3). They also receive dexamethasone IV over 5-10 minutes on days -7 to -3, oral aprepitant on days -7 to -5, and palonosetron hydrochloride IV over 30 seconds on days -7 to -3 and on day 3. Patients undergo HSCT on day 0.

Drug: aprepitant

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Drug: carmustine

Given IV

Drug: cyclophosphamide

Given IV

Drug: cytarabine

Given IV

Drug: dexamethasone

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Drug: etoposide

Given IV

Drug: palonosetron hydrochloride

Dexamethasone and palonosetron hydrochloride are given IV; aprepitant is given orally

Procedure: autologous hematopoietic stem cell transplantation

Patients undergo HSCT on day 0

Detailed Description:

OBJECTIVES:

Primary

To assess emetic responses to multi-day doses of palonosetron hydrochloride and aprepitant in combination with low-dose dexamethasone with or without prochlorperazine in patients with multiple myeloma or lymphoma undergoing high-dose chemotherapy and autologous hematopoietic stem cell transplantation, utilizing the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT).

Secondary

To assess the impact of nausea and vomiting on the quality of life of these patients using the "modified" Osoba module.
To evaluate non-hematologic toxicities in patients treated with this regimen.

OUTLINE: Patients are stratified according to diagnosis (multiple myeloma vs lymphoma).

Group 1 (multiple myeloma): Patients receive high-dose chemotherapy for multiple myeloma (comprising melphalan IV on days -3 to -2). They also receive dexamethasone IV over 5-10 minutes and oral aprepitant on days -3 to -1 and palonosetron hydrochloride IV over 30 seconds on days -3 and -2 and on day 3. Patients undergo HSCT on day 0.
Group 2 (lymphoma): Patients receive high-dose chemotherapy for lymphoma (comprising carmustine IV once on day -7, cytarabine IV twice daily and etoposide IV twice daily on days -6 to -3, and cyclophosphamide once daily on days -6 to -3). They also receive dexamethasone IV over 5-10 minutes on days -7 to -3, oral aprepitant on days -7 to -5, and palonosetron hydrochloride IV over 30 seconds on days -7 to -3 and on day 3. Patients undergo HSCT on day 0.

Patients may receive prochlorperazine or promethazine hydrochloride, lorazepam*, metoclopramide hydrochloride, scopolamine, diphenhydramine hydrochloride or dronabinol as rescue medications for breakthrough emesis.

NOTE: *The single dose lorazepam given prior to HSCT is not considered rescue medication.

Patients in both groups complete a daily diary documenting and rating episodes of nausea and vomiting beginning 24 hours after initiation of the first dose of chemotherapy until day 7 post-transplantation. Patients also complete the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) and modified Osoba module questionnaires for quality of life assessment beginning 24 hours after initiation of the first dose of chemotherapy and on days -6 to -1 and on days 3 and 7.

PROJECTED ACCRUAL: A total of 20 patients (10 multiple myeloma patients and 10 lymphoma patients) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma or lymphoma
Candidate for high-dose chemotherapy and autologous hematopoietic stem cell transplantation as deemed by the treating institution
Must have at least 2.5 x 10^6 cryopreserved CD34+ cells/kg available for transplantation
No primary or secondary brain neoplasms with increased intracranial pressure
No nausea or vomiting episodes

PATIENT CHARACTERISTICS:

Inclusion criteria:

18-75 years of age (multiple myeloma patients)
18-65 years of age (lymphoma patients)
Karnofsky performance status 60-100%
ANC ≥ 1,000/mm³
Platelets ≥ 75,000/mm³
Serum bilirubin < 2.5 mg/dL
Liver function test ≤ 1.5 times upper limit of normal
Calculated creatinine clearance of 50% (lymphoma patients only)
Not pregnant or nursing
Negative pregnancy test
Multiple myeloma patients undergoing hemodialysis are eligible
LVEF ≥ 48% by MUGA scan
Room air pulse oximetry ≥ 93%
FEV_1 and DLCO ≥ 50% of predicted values
Must be able to complete the antiemesis assessment questionnaire

Exclusion criteria:

Active infection requiring intravenous antibiotics
Known active hepatitis B and/or hepatitis C infections
HIV infection
Prior malignancies at other sites except surgically treated nonmelanoma skin cancer, prostate 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 disease (i.e., congestive heart failure, coronary artery disease, or arrhythmias)
- Pulmonary disease
- Hepatic disease
- Renal disease, unless renal insufficiency is felt to be secondary to multiple myeloma
Myocardial infarction within the past 6 months
Morbid obesity (BMI > 40)
Psychiatric or CNS disorders interfering with ability to comply with study protocol
Known hypersensitivity to 5-HT3 antagonists and aprepitant and their components

PRIOR CONCURRENT THERAPY:

At least 24 hours since prior intrathecal chemotherapy
More than 4 weeks since prior major surgery
Not receiving any antiemetic medication within 24 hours of receiving study medications
No concurrent therapeutic anticoagulant therapy for venous thromboembolic episode or other hypercoagulable states
- Coumadin 1 mg for central venous catheter prophylaxis allowed
More than 72 hours since prior and no concurrent use of non-prescription or herbal-type medications
- Concurrent multivitamins without iron, nutritional supplements (i.e., Boost), and other electrolyte replacements allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00631930

Locations

United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Recruiting
Kansas City, Kansas, United States, 66160-7357
Contact: Clinical Trials Office - Kansas Masonic Cancer Research Instit 913-588-4709

Sponsors and Collaborators

University of Kansas

Investigators

Study Chair:

Delva Deauna-Limayo, MD

University of Kansas

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000583228, KUMC-10862, MGI-KUMC-10862
Study First Received:	March 7, 2008
Last Updated:	November 13, 2008
ClinicalTrials.gov Identifier:	NCT00631930
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

nausea and vomiting
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma

stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma

Study placed in the following topic categories:

Dexamethasone
Sezary syndrome
Signs and Symptoms, Digestive
Lymphoma, Mantle-Cell
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Lymphoma, large-cell, immunoblastic
Mycoses
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Etoposide
Hodgkin Disease
Aprepitant
Chronic lymphocytic leukemia

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Leukemia, B-cell, chronic
Carmustine
Serotonin
Multiple Myeloma
Palonosetron
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Melphalan
Vomiting
Hodgkin's disease

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Neurotransmitter Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Serotonin Antagonists
Therapeutic Uses
Cardiovascular Diseases

Alkylating Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Gastrointestinal Agents
Immunosuppressive Agents
Antiviral Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms
Serotonin Agents
Autonomic Agents
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009