Phase 2 Study IV QUZYTTIR™ (Cetirizine Hydrochloride Injection) vs V Diphenhydramine

Study Overview
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Brief Summary
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This study is designed to compare the number of infusion reactions to treatment with an anti-CD20 such as Rituxan® (rituximab) or Taxol® (Paclitaxel) after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment with an anti-CD20 such as Rituxan® (rituximab) or Paclitaxel. Re-treatment is defined as re-treatment with an anti-CD20 such as Rituxan® (rituximab) or Paclitaxel after 6 months or in patients with persistent infusion reactions while on maintenance or retreatment.

Detailed Description
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This will be a randomized, double-blind exploratory study of IV cetirizine HCl 10 mg/mL versus IV diphenhydramine 50 mg/mL in approximately 34 patients who require premedication for hypersensitivity infusion reactions associated with an anti-CD20 such as Rituxan® (rituximab) or Paclitaxel. The objectives and purpose of the study will be described to patients presenting at the participating infusion centers. The patients will be randomized to receive either IV cetirizine HCl or IV diphenhydramine.

Official Title
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A Phase 2 Exploratory Study of Intravenous QUZYTTIR™ (Cetirizine Hydrochloride Injection) Versus Intravenous Diphenhydramine in the Prevention of Hypersensitivity Infusion Reactions

Conditions
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Oncology Patients Receiving Chemotherapy

Intervention / Treatment
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* Drug: Cetirizine HCl 10 mg/mL
* Drug: Diphenhydramine 50 mg/mL
* Drug: anti-CD20 such as Rituximab or Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients who require treatment premedication with an antihistamine for hypersensitivity infusion reactions associated with an anti-CD20, such as Rituxan® (Rituximab) or Paclitaxel, in their first-cycle or re-treatment after 6 months or in patients with persistent infusion reactions while on maintenance or re-treatment. 18 years of age or older Exclusion Criteria: Receipt of an investigational drug or device within the past 30 days. Patients with likelihood of developing or history of tumor lysis syndrome.(TLS): patients with auto-lyse, Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL) with bulky disease (single node 7 or more cm or 3 or more nodal sites with size 3 or more cm) Patients in whom an antihistamine may be contraindicated (e.g., narrow angle glaucoma, symptomatic prostatic hypertrophy). Patients who, in the opinion of the investigator, may not tolerate an IV injection of diphenhydramine 50 mg or cetirizine HCl 10 mg. Receipt of any antihistamine (H1 antagonist) within the past 2 hours regardless of the route of administration, e.g., diphenhydramine, cetirizine, loratadine, fexofenadine, levocetirizine, desloratadine. chlorpheniramine, clemastine, and doxylamine Receipt of an H2 antagonist within the past 4 hours, e.g., ranitidine, cimetidine, famotidine, nizatidine. Receipt of doxepin within the past 24 hours; doxepin is an antidepressant, but it also has antihistamine properties. Receipt of epinephrine (EpiPen® or any other brand) within the past 30 days. Has known allergy to hydroxyzine, cetirizine, or levocetirizine, or diphenhydramine. Pregnant or breastfeeding. Any condition that in the view of the investigator makes the patient unsuitable for enrollment in this study. Major medical or psychiatric illness, other than diagnosed cancer at the time of presentation or in the past that in the investigator's judgement they should not be enrolled in this clinical trial. Inability to provide informed consent. Patients on concomitant P-glycoprotein inhibitors; including antidepressants, antipsychotics (e.g., olanzapine), and benzodiazepines (e.g., alprazolam), as they may cause an increase in sedation. Receipt of drugs that cause sedation within the past 24 hours prior to administration of the study drug.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Randomized Double Blind Study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort A<br>Cetirizine HCl 10 mg/mL: a single 1 mL injection. | Drug: Cetirizine HCl 10 mg/mL<br>* Comparison of two injectable products: cetirizine HCl 10 mg/mL and diphenhydramine 50 mg/mL, both administered during a 1 to 2-minute period by IV push using a 1 mL syringe<br>* Other names: Quzyttir™;Drug: anti-CD20 such as Rituximab or Paclitaxel<br>* Compare the number of infusion reactions to treatment with an anti-CD20 such as Rituxan® (Rituximab) or Taxol® (Paclitaxel) after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment. Re-treatment is defined as re-treatment with Rituxan® (Rituximab) or Paclitaxel after 6 months in patients with persistent infusion reactions while on maintenance or re-treatment.<br>* Other names: Zevalin;|
| Active Comparator: Cohort B<br>Diphenhydramine 50 mg/mL: a single 1 mL injection. | Drug: Diphenhydramine 50 mg/mL<br>* Comparison of two injectable products: cetirizine HCl 10 mg/mL and diphenhydramine 50 mg/mL, both administered during a 1 to 2-minute period by IV push using a 1 mL syringe<br>* Other names: Benadryl injection®;Drug: anti-CD20 such as Rituximab or Paclitaxel<br>* Compare the number of infusion reactions to treatment with an anti-CD20 such as Rituxan® (Rituximab) or Taxol® (Paclitaxel) after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment. Re-treatment is defined as re-treatment with Rituxan® (Rituximab) or Paclitaxel after 6 months in patients with persistent infusion reactions while on maintenance or re-treatment.<br>* Other names: Zevalin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Hypersensitivity Reactions to Treatment With an Anti-CD20 Antibody or Paclitaxel | Compare the number of patients experiencing any infusion reaction events, and the number and percentage of patients experiencing each symptom of infusion reactions (ﬂushing, itching, alterations in heart rate and blood pressure, dyspnea, chest discomfort, acute back or abdominal pain, fever, shaking chills, nausea, vomiting, diarrhea, skin rashes, throat tightening, hypoxia, seizures, dizziness, or syncope) to treatment with anti-CD20 such as Rituxan® (rituximab) or Paclitaxel after premedication with intravenous (IV) QUZYTTIR™ cetirizine hydrochloride (HCl) or IV diphenhydramine during first-cycle infusion or re-treatment after 6 months or in patients with persistent infusion reactions while on maintenance with anti-CD20 such as Rituxan® (rituximab) or Paclitaxel. The infusion reactions will be evaluated following the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) deﬁnitions of graded infusion reactions. | During and after anti-CD20 agent or paclitaxel infusion, at 1 and 2 hours after the antihistamine injection, at time of discharge, and up through 1 Month post injection of antihistamine (intervention). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Sedation Scores at 1 Hour and 2 Hours Post-injection of Antihistamine (IV Cetirizine HCl or IV Diphenhydramine) and at Discharge. | Patient sedation scores at 1 hour and 2 hours post-injection of antihistamine (IV cetirizine HCl or IV diphenhydramine) and at discharge. The patient sedation scores are assessed on a scale of 0-4, with 0=None and 4=Extremely Severe (Asleep, Cannot Self-Rate). The HCP sedation scores are assessed on a scale of 0-4, with 0=None and 4=Extremely severe. | 1 hour, 2 Hours and at discharge | 
| Time From Injection to Readiness for Discharge | Describe the distribution of the amount of time spent in the treatment center prior to discharge (time from injection to Readiness for Discharge). | Time to discharge from infusion center |