Aprepitant in Preventing Nausea and Vomiting in Patients Who Are Undergoing a Stem Cell Transplant

• ClinicalTrials.gov Identifier: NCT00248547
• Recruitment Status: Completed
• First Posted: November 4, 2005
• Results First Posted: December 21, 2011
• Last Update Posted: May 9, 2017
• Sponsor: OHSU Knight Cancer Institute
• Information provided by (Responsible Party): Joseph Bubalo, OHSU Knight Cancer Institute

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Cancer	Drug: aprepitant; Drug: dexamethasone; Drug: ondansetron; Drug: placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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)
• Study Start Date: May 2004
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: January 2009

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Number of Emesis Free Participants During the Study Period. [ Time Frame: Up to three weeks ]
   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 :

1. Safety in Transplant Population [ Time Frame: Up to three weeks ]
   To assess the safety of aprepitant in the bone marrow transplant population
2. Effects on Nausea, Appetite and Taste Changes [ Time Frame: Up to three weeks ]
   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.
3. Pharmacokinetic Interaction [ Time Frame: Up to three weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Joseph Bubalo, PharmD, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00248547
• Other Study ID Numbers: CDR0000445452; OHSU-HEM-03074-L ( Other Identifier: OHSU Knight Cancer Institute ); OHSU-1057 ( Other Identifier: OHSU IRB ); MERCK-OHSU-HEM-03074-L ( Other Identifier: Merck )
• First Posted: November 4, 2005
• Results First Posted: December 21, 2011
• Last Update Posted: May 9, 2017
• Last Verified: May 2017

Keywords provided by Joseph Bubalo, 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:

Nausea; Vomiting; Signs and Symptoms, Digestive; Dexamethasone; Ondansetron; Aprepitant; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antipruritics; Dermatologic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Anti-Anxiety Agents; Neurokinin-1 Receptor Antagonists