Aprepitant in Preventing Nausea and Vomiting in Patients Who Are Undergoing a Stem Cell Transplant - Full Text View

Sponsor:	OHSU Knight Cancer Institute
Information provided by (Responsible Party):	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00248547

Purpose

RATIONALE: Antiemetic drugs, such as aprepitant, ondansetron, and dexamethasone, may help lessen or prevent nausea and vomiting in patients undergoing a stem cell transplant.

PURPOSE: This randomized clinical trial is studying aprepitant, ondansetron, and dexamethasone to see how well they work compared to placebo, ondansetron, and dexamethasone in preventing nausea and vomiting in patients who are undergoing a stem cell transplant.

Condition	Intervention
Cancer	Drug: aprepitant Drug: dexamethasone Drug: ondansetron Drug: placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
Official Title:	A Pilot Study of Aprepitant vs. Placebo Combined With Standard Antiemetics for the Control of Nausea and Vomiting During Hematopoietic Cell Transplatation(HCT)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer neuroblastoma

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Hodgkin Disease Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes Nausea and Vomiting Neuroblastoma

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Ondansetron hydrochloride Ondansetron Aprepitant Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:

Number of Emesis Free Participants During the Study Period. [ Time Frame: Up to three weeks ] [ Designated as safety issue: No ]
To compare the efficacy of aprepitant plus standard therapy to placebo plus standard therapy in control of nausea and vomiting during conditioning therapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) as defined by the number of retch/emesis free days during the study period

Secondary Outcome Measures:

Safety in Transplant Population [ Time Frame: Up to three weeks ] [ Designated as safety issue: Yes ]
To assess the safety of aprepitant in the bone marrow transplant population
Effects on Nausea, Appetite and Taste Changes [ Time Frame: Up to three weeks ] [ Designated as safety issue: No ]
To assess the effects of aprepitant on nausea, appetite, and taste changes, (via visual analogue scale [VAS]), nutritional intake, and mucositis in the bone marrow transplant population.
Pharmacokinetic Interaction [ Time Frame: Up to three weeks ] [ Designated as safety issue: No ]
To assess the potential for aprepitant and cyclophosphamide to interact pharmacokinetically in a significant manner to change blood levels of aprepitant, cyclophosphamide, hydroxycyclophosphamide or CEPM.

Enrollment:	40
Study Start Date:	May 2004
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Aprepitant	Drug: aprepitant Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant Other Name: Emend Drug: dexamethasone For Cyclophosphamide Total Body Irradiation(CyTBI) patients: Dexamethasone study drug 1 capsule PO daily, 1 hour prior to chemotherapy with aprepitant on total body irradiation(TBI) and cyclophosphamide chemotherapy days; For Busulfan Cyclophosphamide(BuCy) patients: Dexamethasone 1 capsule orally once daily, discontinue after last dose of chemotherapy. Other Name: Decadron Drug: ondansetron For CyTBI patients: Ondansetron 8 mg orally evert 12 hours, begin 1 hour prior to first TBI dose and discontinue after last dose; then Ondansetron 8 mg IV every 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy; For BuCy patients: Ondansetron 8 mg orally every 6 hours, begin 1 hour prior to first busulfan dose and discontinue after last busulfan dose is given. then: Ondansetron 8 mg IV Q 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy Other Name: Zofran
Placebo Comparator: sugar pill Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant	Drug: dexamethasone For Cyclophosphamide Total Body Irradiation(CyTBI) patients: Dexamethasone study drug 1 capsule PO daily, 1 hour prior to chemotherapy with aprepitant on total body irradiation(TBI) and cyclophosphamide chemotherapy days; For Busulfan Cyclophosphamide(BuCy) patients: Dexamethasone 1 capsule orally once daily, discontinue after last dose of chemotherapy. Other Name: Decadron Drug: ondansetron For CyTBI patients: Ondansetron 8 mg orally evert 12 hours, begin 1 hour prior to first TBI dose and discontinue after last dose; then Ondansetron 8 mg IV every 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy; For BuCy patients: Ondansetron 8 mg orally every 6 hours, begin 1 hour prior to first busulfan dose and discontinue after last busulfan dose is given. then: Ondansetron 8 mg IV Q 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy Other Name: Zofran Drug: placebo Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant Other Name: placebo, sugar pill

Arms

Assigned Interventions

Active Comparator: Aprepitant

Drug: aprepitant

Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant

Other Name: Emend

Drug: dexamethasone

For Cyclophosphamide Total Body Irradiation(CyTBI) patients: Dexamethasone study drug 1 capsule PO daily, 1 hour prior to chemotherapy with aprepitant on total body irradiation(TBI) and cyclophosphamide chemotherapy days; For Busulfan Cyclophosphamide(BuCy) patients: Dexamethasone 1 capsule orally once daily, discontinue after last dose of chemotherapy.

Other Name: Decadron

Drug: ondansetron

For CyTBI patients: Ondansetron 8 mg orally evert 12 hours, begin 1 hour prior to first TBI dose and discontinue after last dose; then Ondansetron 8 mg IV every 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy; For BuCy patients: Ondansetron 8 mg orally every 6 hours, begin 1 hour prior to first busulfan dose and discontinue after last busulfan dose is given. then: Ondansetron 8 mg IV Q 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy

Other Name: Zofran

Placebo Comparator: sugar pill

Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant

Drug: dexamethasone

For Cyclophosphamide Total Body Irradiation(CyTBI) patients: Dexamethasone study drug 1 capsule PO daily, 1 hour prior to chemotherapy with aprepitant on total body irradiation(TBI) and cyclophosphamide chemotherapy days; For Busulfan Cyclophosphamide(BuCy) patients: Dexamethasone 1 capsule orally once daily, discontinue after last dose of chemotherapy.

Other Name: Decadron

Drug: ondansetron

For CyTBI patients: Ondansetron 8 mg orally evert 12 hours, begin 1 hour prior to first TBI dose and discontinue after last dose; then Ondansetron 8 mg IV every 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy; For BuCy patients: Ondansetron 8 mg orally every 6 hours, begin 1 hour prior to first busulfan dose and discontinue after last busulfan dose is given. then: Ondansetron 8 mg IV Q 12 hours X 4 doses, begin 30 minutes prior to first cyclophosphamide chemotherapy

Other Name: Zofran

Drug: placebo

Loading dose of 125 mg capsule once a day for one day, then maintenance dose of 80 mg capsule daily through Day +4 of Bone Marrow Transplant

Other Name: placebo, sugar pill

Detailed Description:

OBJECTIVES:

Primary

Compare the efficacy of standard antiemetic therapy comprising ondansetron and dexamethasone combined with either aprepitant or placebo in controlling nausea and vomiting, as determined by the number of retch/emesis-free days, in patients undergoing hematopoietic stem cell transplantation.

Secondary

Determine the safety of aprepitant in these patients.
Compare nausea, appetite, taste changes, nutritional intake, and mucositis in patients treated with these regimens.
Determine the pharmacokinetics of cyclophosphamide, carboxyethylphosphoramide mustard, hydroxycyclophylamide, and aprepitant in these patients.

OUTLINE: This is a randomized, placebo-controlled, single-blind, pilot study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Beginning on the first day of conditioning chemotherapy, patients receive oral aprepitant once daily and standard antiemetic therapy comprising oral or IV ondansetron and oral dexamethasone.
Arm II: Patients receive oral placebo once daily and standard antiemetic therapy as in arm I.

In both arms, treatment continues until day 4 after stem cell transplant in the absence of unacceptable toxicity.

After completion of study therapy, patients are followed until day 18.

PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion:

18 years of age or greater
must be scheduled for an autologous or allogeneic bone marrow or peripheral stem cell transplant
Eastern Cooperative Oncology Group(ECOG) performance status < or = 2
patients must have signed informed consent
must be able to swallow tablets and capsules
must be receiving a cyclophosphamide containing regimen.

Exclusion:

patient has known sensitivity to aprepitant, ondansetron, or dexamethasone
patient has received another investigational drug in the past 30 days
patient has had emesis or requires antiemetic agents in the 48 hours prior to beginning conditioning therapy
patient has taken neurokinin-1 antagonists for 14 days prior to enrollment
patient is pregnant, has a positive serum human chorionic gonadotropin(hCg) or is lactating
patient has serum creatinine level > or = 2*ULN
patient has severe hepatic insufficiency (Child-Pugh score >9)
patient drinks > 5 drinks/day for the last year
patient with concurrent illness requiring systemic corticosteroid use other than planned dexamethasone during conditioning therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00248547

Locations

United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239-3098

Sponsors and Collaborators

OHSU Knight Cancer Institute

Investigators

Principal Investigator:

Joseph Bubalo, PharmD

OHSU Knight Cancer Institute

More Information

Additional Information:

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

No publications provided

Responsible Party:	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00248547 History of Changes
Other Study ID Numbers:	CDR0000445452, OHSU-HEM-03074-L, OHSU-1057, MERCK-OHSU-HEM-03074-L
Study First Received:	November 3, 2005
Results First Received:	November 21, 2011
Last Updated:	December 20, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:

nausea and vomiting
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia

chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma

Additional relevant MeSH terms:

Lymphoma, Non-Hodgkin
Nausea
Vomiting
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone

Ondansetron
Aprepitant
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on February 12, 2012