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The purpose of this study is to help answer the following research question:
Whether administration of an aprepitant containing regimen, an olanzapine containing regimen or regimen containing both will prevent nausea and vomiting better for patients undergoing an autologous stem cell transplant with melphalan chemotherapy. Both of these medications are approved by the United States Food and Drug Administration (FDA) for nausea and vomiting.
Participants will be randomly assigned to one of the 3 treatment groups:
This is a multi-center, randomized, non-inferiority phase 3 study conducted to determine an appropriate anti-emetic regimen for patients receiving melphalan for an autologous stem cell transplant (SCT). Candidates for this trial will include patients aged 18-80 years with hematologic malignancies receiving high dose melphalan as part of a conditioning regimen for an autologous stem cell transplant. Patients will be enrolled in 3 arms. Patients in Arm A will receive an aprepitant containing anti-emetic regimen. Patients in Arm B will receive an olanzapine containing anti-emetic regimen. Patients in Arm C will receive an aprepitant plus olanzapine containing anti-emetic regimen. Patients must be able to tolerate oral medications.
Patients will be carefully monitored for rates of emesis, nausea, and mucositis. Any adverse events will be recorded. Impact on quality of life will also be assessed. A total of 184 patients will be accrued to each arm. It is anticipated that the accrual period will last approximately 2-3 years. The primary endpoint of this study is a complete response, defined as no emesis and no rescue therapy within 120 hours of melphalan administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aprepitant | Active Comparator | aprepitant plus standard anti-emetic regimen |
|
| Olanzapine | Experimental | olanzapine plus standard anti-emetic regimen |
|
| Aprepitant plus olanzapine | Experimental | aprepitant and olanzapine plus standard anti-emetic regimen |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| o Aprepitant 125 mg orally one hour prior to chemotherapy on Day -1 and 80 mg orally on Days 0 and +1 | Drug | Add aprepitant to anti-emetic regimen |
|
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response (CR) | no emesis and no rescue anti-emetic therapy | within 120 hours following melphalan administration; no emesis and no rescue therapy within 120 hours of melphalan administration (within 120 hours following last day of melphalan administration at baseline) |
| Measure | Description | Time Frame |
|---|---|---|
| Acute Complete Response | no emesis or rescue therapy; Acute complete response defined as no emesis or rescue therapy required from time point of 0 to 24 hours following melphalan therapy administration | 0 (transplant time) to 24 hours post-transplant |
| Delayed Complete Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathryn Schultz, PharmD | Rush University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21947834 | Background | Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, Chesney M, Clark-Snow RA, Flaherty AM, Freundlich B, Morrow G, Rao KV, Schwartz RN, Lyman GH; American Society of Clinical Oncology. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011 Nov 1;29(31):4189-98. doi: 10.1200/JCO.2010.34.4614. Epub 2011 Sep 26. | |
| 22024310 |
| Label | URL |
|---|---|
| Multinational Association Of Supportive Care In Cancer (MASCC)/European Society of Medical Oncology (ESMO) Antiemetic Guidelines 2013 | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Aprepitant | aprepitant plus standard anti-emetic regimen Aprepitant: Add aprepitant to anti-emetic regimen |
| FG001 | Olanzapine | olanzapine plus standard anti-emetic regimen Olanzapine: add olanzapine to anti-emetic regimen |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Nov 22, 2021 |
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| Olanzapine10 mg orally daily on Days -1,0,+1 and +2 | Drug | add olanzapine to anti-emetic regimen |
|
|
| Aprepitant plus Olanzapine | Drug | add aprepitant and olanzapine to anti-emetic regimen |
|
|
no emesis or rescue therapy administered; Delayed complete response defined as no emesis or rescue therapy required from time point of 25 hours to 120 hours following melphalan therapy administration |
| 25-120 hours post-transplant |
| Background |
| Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011 Sep-Oct;9(5):188-95. doi: 10.1016/j.suponc.2011.05.002. Epub 2011 Sep 24. |
| 20935058 | Background | Giralt SA, Mangan KF, Maziarz RT, Bubalo JS, Beveridge R, Hurd DD, Mendoza FL, Rubenstein EB, DeGroot TJ, Schuster MW. Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation. Ann Oncol. 2011 Apr;22(4):939-946. doi: 10.1093/annonc/mdq457. Epub 2010 Oct 8. |
| 11130251 | Background | Slaby J, Trneny M, Prochazka B, Klener P. Antiemetic efficacy of three serotonin antagonists during high-dose chemotherapy and autologous stem cell transplantation in malignant lymphoma. Neoplasma. 2000;47(5):319-22. |
| 11781617 | Background | Ballen KK, Hesketh AM, Heyes C, Becker PS, Emmons RV, Fogarty K, LaPointe J, Liu Q, Hsieh CC, Hesketh PJ. Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support. Bone Marrow Transplant. 2001 Dec;28(11):1061-6. doi: 10.1038/sj.bmt.1703280. |
| 20505956 | Background | Einhorn LH, Grunberg SM, Rapoport B, Rittenberg C, Feyer P. Antiemetic therapy for multiple-day chemotherapy and additional topics consisting of rescue antiemetics and high-dose chemotherapy with stem cell transplant: review and consensus statement. Support Care Cancer. 2011 Mar;19 Suppl 1:S1-4. doi: 10.1007/s00520-010-0920-z. Epub 2010 May 26. |
| 20838387 | Background | Jordan K, Jahn F, Jahn P, Behlendorf T, Stein A, Ruessel J, Kegel T, Schmoll HJ. The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant. 2011 Jun;46(6):784-9. doi: 10.1038/bmt.2010.205. Epub 2010 Sep 13. |
| 21996238 | Background | Pielichowski W, Barzal J, Gawronski K, Mlot B, Oborska S, Wasko-Grabowska A, Rzepecki P. A triple-drug combination to prevent nausea and vomiting following BEAM chemotherapy before autologous hematopoietic stem cell transplantation. Transplant Proc. 2011 Oct;43(8):3107-10. doi: 10.1016/j.transproceed.2011.08.010. |
| 22863840 | Background | Stiff PJ, Fox-Geiman MP, Kiley K, Rychlik K, Parthasarathy M, Fletcher-Gonzalez D, Porter N, Go A, Smith SE, Rodriguez TE. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013 Jan;19(1):49-55.e1. doi: 10.1016/j.bbmt.2012.07.019. Epub 2012 Aug 1. |
| 11997204 | Background | Khojainova N, Santiago-Palma J, Kornick C, Breitbart W, Gonzales GR. Olanzapine in the management of cancer pain. J Pain Symptom Manage. 2002 Apr;23(4):346-50. doi: 10.1016/s0885-3924(02)00378-0. |
| 11711053 | Background | Bymaster FP, Falcone JF, Bauzon D, Kennedy JS, Schenck K, DeLapp NW, Cohen ML. Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol. 2001 Nov 2;430(2-3):341-9. doi: 10.1016/s0014-2999(01)01399-1. |
| 16983116 | Background | Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients' quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006 Sep 20;24(27):4472-8. doi: 10.1200/JCO.2006.05.6382. |
| 25225424 | Background | Schmitt T, Goldschmidt H, Neben K, Freiberger A, Husing J, Gronkowski M, Thalheimer M, Pelzl le H, Mikus G, Burhenne J, Ho AD, Egerer G. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol. 2014 Oct 20;32(30):3413-20. doi: 10.1200/JCO.2013.55.0095. Epub 2014 Sep 15. |
| 12827483 | Background | Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C. Assessing the impact of chemotherapy-induced nausea and vomiting on patients' daily lives: a modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall. Support Care Cancer. 2003 Aug;11(8):522-7. doi: 10.1007/s00520-003-0482-4. Epub 2003 Jun 25. |
| FG002 | Aprepitant Plus Olanzapine | aprepitant and olanzapine plus standard anti-emetic regimen Aprepitant plus Olanzapine: add aprepitant and olanzapine to anti-emetic regimen |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Aprepitant | aprepitant plus standard anti-emetic regimen Aprepitant: Add aprepitant to anti-emetic regimen |
| BG001 | Olanzapine | olanzapine plus standard anti-emetic regimen Olanzapine: add olanzapine to anti-emetic regimen |
| BG002 | Aprepitant Plus Olanzapine | aprepitant and olanzapine plus standard anti-emetic regimen Aprepitant plus Olanzapine: add aprepitant and olanzapine to anti-emetic regimen |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Conditioning Chemotherapy Regimen | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Response (CR) | no emesis and no rescue anti-emetic therapy | Posted | Count of Participants | Participants | within 120 hours following melphalan administration; no emesis and no rescue therapy within 120 hours of melphalan administration (within 120 hours following last day of melphalan administration at baseline) |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Acute Complete Response | no emesis or rescue therapy; Acute complete response defined as no emesis or rescue therapy required from time point of 0 to 24 hours following melphalan therapy administration | No data were collected or analyzed for this outcome. | Posted | 0 (transplant time) to 24 hours post-transplant |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Delayed Complete Response | no emesis or rescue therapy administered; Delayed complete response defined as no emesis or rescue therapy required from time point of 25 hours to 120 hours following melphalan therapy administration | No data were collected or analyzed for this outcome. | Posted | 25-120 hours post-transplant |
|
|
Patients were monitored for 3 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aprepitant | aprepitant plus standard anti-emetic regimen Aprepitant: Add aprepitant to anti-emetic regimen | 0 | 14 | 3 | 14 | 0 | 14 |
| EG001 | Olanzapine | olanzapine plus standard anti-emetic regimen Olanzapine: add olanzapine to anti-emetic regimen | 21 | 21 | 3 | 21 | 0 | 21 |
| EG002 | Aprepitant Plus Olanzapine | aprepitant and olanzapine plus standard anti-emetic regimen Aprepitant plus Olanzapine: add aprepitant and olanzapine to anti-emetic regimen | 0 | 8 | 1 | 8 | 0 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mucositis | Gastrointestinal disorders | mucositis | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Danielle Murphy, PharmD, BCOP, BCPS | Rush University Medical Center | 3129472401 | danielle_murphy@rush.edu |
| Jan 18, 2024 |
| Prot_SAP_ICF_003.pdf |
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| ID | Term |
|---|---|
| D009325 | Nausea |
| D014839 | Vomiting |
| D054219 | Neoplasms, Plasma Cell |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077608 | Aprepitant |
| D000077152 | Olanzapine |
| ID | Term |
|---|---|
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
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| African American |
|
| Hispanic |
|
| Asian |
|
| 1-day melphalan |
|
| 2-day melphalan |
|
| Participants |
|