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
Conditions
Keywords
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, BCR-ABL negative, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, primary 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 neoplasm, 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, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, poor prognosis metastatic gestational trophoblastic tumor, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent neuroblastoma, recurrent ovarian epithelial cancer, recurrent ovarian germ cell tumor, recurrent small lymphocytic lymphoma, recurrent malignant testicular germ cell tumor, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, refractory multiple myeloma, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, splenic marginal zone lymphoma, stage I multiple myeloma, stage II multiple myeloma, stage II ovarian epithelial cancer, stage III adult Burkitt lymphoma, stage III adult Hodgkin 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 immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III chronic lymphocytic leukemia, 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 multiple myeloma, stage III ovarian epithelial cancer, stage III small lymphocytic lymphoma, stage III malignant testicular germ cell tumor, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV adult Burkitt lymphoma, stage IV adult Hodgkin 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 immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV breast cancer, stage IV chronic lymphocytic leukemia, 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 ovarian epithelial cancer, stage IV small lymphocytic lymphoma
Brief summary
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.
Detailed description
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.
Interventions
DRUGAprepitant
Aprepitant 80mg once daily in the morning on days 2 and 3
DRUGCyclophosphamide
Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes
DRUGDexamethasone
Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration.
Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Controlled Acute Vomiting | at 0-24 hours | No episodes of vomiting and no rescue medication during first 24 hours after cyclophosphamide administration. |
Secondary
| Measure | Time frame |
|---|---|
| Delayed Vomiting Controlled | at 25-120 hours |
| Toxicity Grade 3, 4, or 5 | at 0-120 hours |
Other
| Measure | Time frame |
|---|---|
| Overall Nausea Controlled | at 0-120 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant, Dexamethasone, Cytoxan & Kytril Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration.
Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes.
Days 2 & 3: Aprepitant 80 mg once daily in the morning.
Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3
Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes
Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration.
Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 2 |
| Overall Study | Missed dosage/study drug | 1 |
| Overall Study | Non-compliance | 2 |
Baseline characteristics
| Characteristic | Aprepitant, Dexamethasone, Cytoxan & Kytril |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 35 |
| serious Total, serious adverse events | 10 / 35 |
Outcome results
Primary
Proportion of Participants With Controlled Acute Vomiting
No episodes of vomiting and no rescue medication during first 24 hours after cyclophosphamide administration.
Time frame: at 0-24 hours
Population: Evaluable for response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant, Dexamethasone, Cytoxan & Kytril | Proportion of Participants With Controlled Acute Vomiting | 20 participants |
Comparison: Optimal Simon design for phase II study. p0=45% p1=65%.p-value: 0.1Simon optimal design
Secondary
Delayed Vomiting Controlled
Time frame: at 25-120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant, Dexamethasone, Cytoxan & Kytril | Delayed Vomiting Controlled | 22 participants |
Secondary
Toxicity Grade 3, 4, or 5
Time frame: at 0-120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant, Dexamethasone, Cytoxan & Kytril | Toxicity Grade 3, 4, or 5 | 2 participants |
Other Pre-specified
Overall Nausea Controlled
Time frame: at 0-120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant, Dexamethasone, Cytoxan & Kytril | Overall Nausea Controlled | 31 participants |