BMT-08: A Comparative Effectiveness Study of Transdermal Granisetron to Ondansetron

Study Overview
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Brief Summary
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Patients undergoing either an autologous or allogeneic hematopoietic stem cell transplant (HSCT) and receiving preparative chemotherapy experience a considerable amount of chemotherapy-induced nausea and vomiting (CINV). Current strategies at reducing CINV in this patient population are suboptimal due to lack of efficacy and supportive evidence, potential for increased adverse events, and drug-drug and drug-disease contraindications.

Detailed Description
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Patients undergoing either an autologous or allogeneic hematopoietic stem cell transplant (HSCT) and receiving preparative chemotherapy experience a considerable amount of chemotherapy-induced nausea and vomiting (CINV). Current strategies at reducing CINV in this patient population are suboptimal due to lack of efficacy and supportive evidence, potential for increased adverse events, and drug-drug and drug-disease contraindications. This study will be an open-label, prospective trial randomizing patients at a 1:1 ratio, to either one of two 5-hydroxytrytamine 3 (5-HT3) antagonists, transdermal granisetron or intravenous (i.v.) ondansetron, in combination with other standard, routinely administered anti-emetic drugs (dexamethasone). Rescue antiemetics will be administered at any time during the study period for vomiting or severe nausea at the request of the patients or as recommended by the attending physicians. For the granisetron treatment arm, patients will be educated and instructed to self-administer a single transdermal granisetron patch one-two days (approximately 24-48 hours) prior to start of the preparative regimen. An additional dose of transdermal granisetron will be administered 7 days after the initial granisetron dose. For the ondansetron treatment arm, patients will receive the standard dose and schedule of intravenous ondansetron that is routinely administered for each respective preparative regimen. Use of rescue medications will be assessed daily during chemotherapy, and for 7 days after the last chemotherapy drug administration (delayed phase). Nausea, vomiting, and treatment-related side effects will be documented and followed during this same time period. A quality of life questionnaire (MDASI-BMT) will be administered at Day + 7 (7 days after day of infusion). All other aspects of patient care (i.e., chemotherapy administration, supportive care, etc.) and laboratory monitoring will adhere to the routine standard of care operating procedures for stem cell transplant patients.

Official Title
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BMT-08: A Comparative Effectiveness Study of the Efficacy and Safety of Transdermal Granisetron to Ondansetron in the Prevention of Nausea and Vomiting in Patients Undergoing Preparative Chemotherapy and Hematopoietic Stem Cell Transplantation

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Granisetron Transdermal Patch
* Drug: Intravenous Dexamethasone
* Drug: Ondansetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years at time of enrollment receiving either a preparative regimen and either an autologous or allogeneic stem cell transplant. No vomiting ≤ 24 hours prior to registration No treatment with an antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for ≤ 30 days' prior registration or planned during protocol therapy. No patients will be removed from these treatments for study enrollment purposes. No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue antiemetic therapy). No patients will be removed from these treatments for study enrollment purposes. No known hypersensitivity to granisetron Exclusion Criteria: Concurrent use of amifostine Known hypersensitivity to granisetron patch or ondansetron Patients with a history of long QT syndrome or Torsade de Pointes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized 1:1 to either Arm 1 transdermal granisetron OR Arm 2 intravenous ondansetron
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>ARM 1 -transdermal granisetron plus intravenous dexamethasone | Drug: Granisetron Transdermal Patch<br>* Antiemetic<br>Drug: Intravenous Dexamethasone<br>* Antiemetic<br>|
| Active Comparator: ARM 2<br>ARM 2 -intravenous ondansetron plus intravenous dexamethasone | Drug: Intravenous Dexamethasone<br>* Antiemetic<br>Drug: Ondansetron<br>* ondansetron<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy/Safety of Transdermal Granisetron for Prevention of CINV | To compare between the two study arms the number of patients achieving complete response (CR, no vomiting and no use of rescue medications during the acute period (0-24 hours post-chemotherapy) for patients receiving preparative chemotherapy and HSCT. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy/Safety of Ondansetron for Prevention of CINV | To compare between the two study arms the number of patients achieving complete response (CR, no vomiting and no use of rescue medications during the delayed (24-120 hours post-chemotherapy) and overall periods (0-120 hours post-chemotherapy) for patients receiving preparative chemotherapy and HSCT. | 2 years | 
| Efficacy/Safety of Ondansetron and Transdermal Granisetron for Prevention of CINV | To compare between the two study arms the number of patients achieving complete response (CR, no vomiting and no use of rescue medications during the overall period (0-120 hours post-chemotherapy) for patients receiving preparative chemotherapy and HSCT. | 2 years | 
| Efficacy/Safety of Ondansetron and Transdermal Granisetron for Prevention of CINV | To compare between the two study arms, the use of rescue anti-emetic medications (during and for 7 days after the preparative regimen) for patients receiving preparative chemotherapy and HSCT. | 2 years | 
| Efficacy/Safety of Ondansetron and Transdermal Granisetron for Prevention of CINV | To compare between the two study arms the occurrence of CINV complete protection, defined as no emetic episode, no use of rescue medications and no nausea, during the acute, delayed, and overall phases for patients receiving preparative chemotherapy and HSCT. | 2 years | 
| Efficacy/Safety of Ondansetron and Transdermal Granisetron for Prevention of CINV | To compare the occurrence of treatment-related adverse events (AE) between patients receiving transdermal granisetron versus intravenous ondansetron. | 2 years | 
| Efficacy/Safety of Ondansetron and Transdermal Granisetron for Prevention of CINV | To compare quality of life using the M.D. Anderson Symptom Inventory (MDASI) Core Items-Bone Marrow Transplant (BMT) scale throughout the course of HSCT 7 days after stem cell infusion, between patients receiving transdermal granisetron versus intravenous ondansetron | 2 years |