Aprepitant, Granisetron, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Cyclophosphamide Before a Stem Cell Transplant

• Delayed vomiting controlled [ Time Frame: at 25-120 hours ] [ Designated as safety issue: Yes ]
• Overall nausea controlled [ Time Frame: at 0-120 hours ] [ Designated as safety issue: Yes ]
• Toxicity grade 3, 4, or 5 [ Time Frame: at 0-120 hours ] [ Designated as safety issue: Yes ]

RATIONALE: Antiemetic drugs, such as aprepitant, granisetron, and dexamethasone, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy.

PURPOSE: This clinical trial is studying how well giving aprepitant together with granisetron and dexamethasone works in preventing nausea and vomiting in patients receiving cyclophosphamide before undergoing an autologous stem cell transplant.

OBJECTIVES:

Primary

• Evaluate the efficacy of the addition of aprepitant in controlling acute vomiting with the standard prophylactic anti-emetic combination of granisetron hydrochloride and dexamethasone in patients receiving therapy comprising high-dose cyclophosphamide to mobilize stem cells prior to leukapheresis for autologous stem cell transplantation.

Secondary

• Evaluate the efficacy of the addition of aprepitant in controlling delayed vomiting in these patients.
• Evaluate the efficacy of the addition of aprepitant in controlling overall nausea in these patients.
• Identify side effects of the addition of aprepitant to this regimen in these patients.

OUTLINE: Patients receive granisetron hydrochloride orally or IV and oral dexamethasone, followed 1 hour later by cyclophosphamide IV over 2 hours on day 1. Patients also receive oral aprepitant once daily on days 1-3. Treatment continues in absence of unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

• Breast Cancer
• Chronic Myeloproliferative Disorders
• Gestational Trophoblastic Tumor
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Neoplasms
• Nausea and Vomiting
• Neuroblastoma
• Ovarian Cancer
• Testicular Germ Cell Tumor

• Drug: Aprepitant
  Aprepitant 80mg once daily in the morning on days 2 and 3
  Other Name: Emend
• Drug: Cyclophosphamide
  Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes
  Other Names:

  • Cytoxan®
  • Neosar®
• Drug: Dexamethasone
  Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration.
  Other Names:

  • Decadron
  • Diodex
  • Hexadrol
  • Maxidex
  • Dexamethasone Sodium Phosphate
  • Dexamethasone Acetate
• Drug: Granisetron hydrochloride
  Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
  Other Name: KYTRIL®

DISEASE CHARACTERISTICS:

• Undergoing autologous peripheral blood stem cell transplantation and stem cell mobilization using cyclophosphamide

• Candidate (per institutional requirements) for autologous peripheral blood stem cell transplantation

  • No psychiatric illness or multi-system organ failure
• No nausea at baseline

PATIENT CHARACTERISTICS:

• SWOG performance status 0-2
• Fewer than 5 alcoholic drinks per day within the past year
• No current illness requiring chronic systemic steroids or requirement for chronic use of anti-emetics
• No gastrointestinal obstruction or active peptic ulcer disease
• AST and ALT ≤ 3 times upper limit of normal (ULN)
• Bilirubin ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ 2 mg/dL
• No known hypersensitivity to any component of the study regimen
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No unrelenting hiccups

PRIOR CONCURRENT THERAPY:

• No chronic therapeutic warfarin > 1 mg dose per day
• No other concurrent investigational agents
• No concurrent oral contraceptives (except for stopping menses), tolbutamide, phenytoin, midazolam, ketoconazole, rifampin, paroxetine hydrochloride, or diltiazem hydrochloride
• No concurrent illegal drugs