Clinical trial NCT02939287: Aprepitant- and Olanzapine- Containing Anti-emetic Regimens With High Dose Melphalan
Official title: Aprepitant- and Olanzapine- Containing Regimens for Prevention of Acute and Delayed Nausea and Vomiting Associated With High Dose Melphalan and BEAM in Autologous Stem Cell Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nausea
Vomiting
Keywords: autologous
myeloma
transplant
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2016-10-20
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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:

  * Arm A: aprepitant containing anti-emetic therapy
  * Arm B: olanzapine containing anti-emetic therapy
  * Arm C: Aprepitant plus olanzapine containing anti-emetic therapy

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Autologous transplant containing high dose melphalan as part of the conditioning regimen (single or 2 day melphalan; BEAM \[carmustine, etoposide, cytarabine, melphalan\])
* able to tolerate oral medications

Exclusion Criteria:

* Nausea/vomiting within 12 hours before planned high dose conditioning chemotherapy
* Any anti-emetic treatment within 24 hours before planned high dose conditioning chemotherapy
* Pregnancy
* Baseline corrected QT interval (QTc) \> 500 ms
* History of seizures
* History of central nervous system (CNS) disease
* Human immunodeficiency virus (HIV)

Primary outcomes:
measure: Complete Response (CR)
timeFrame: 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 outcomes:
measure: Acute Complete Response
timeFrame: 0 (transplant time) to 24 hours post-transplant
measure: Delayed Complete Response
timeFrame: 25-120 hours post-transplant
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Kathryn Schultz, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.