Efficacy of Montelukast in Reducing the Incidence and Severity of Monoclonal Antibodies Associated Infusion Reactions

NCT ID: NCT04198623

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-20
• Study Completion Date: 2024-07-31

Brief Summary

The use of monoclonal antibodies (MA) either alone or as part of chemoimmunotherapy in oncology, benign and malignant hematology is expanding. Of the 17 therapeutic MAs approved in 2017 by FDA, 50% of them are indicated for hematologic and oncologic condition. With increasing number of approved agents, therapeutic MAs have become one of the fastest growing areas in the management of benign and malignant hematologic condition. Advancement of recombinant technology allows development of partially or fully humanized new agents. Despite this, they still carry significant risk of immune and non-immune mediated adverse events. Most of the therapeutic monoclonal antibody related adverse events (MCAAE) The severity of reaction is variable, ranging from mild involvement of single organ to severe and life-threatening reactions requiring hospitalization or even resulting in death.

Even for mild infusion reactions, where re-initiation of infusion is possible, there is resultant delay in delivery of infusions, distress to patients, and additional utilization of health care resources.

Due to unpredictability of standard infusion reaction (SIR), efforts have been focused on premedication to decreasing the incidence and severity of infusion reaction. Most institutions have protocols using corticosteroid, acetaminophen and antihistamine as part of their premedication protocols. This has reduced but not eliminated standard infusion reactions. Most recently, mast cell stabilizers are being added to standard protocols to further reduce the incidence and severity of standard infusion reactions with variable anecdotal success without formal study. Of all the monoclonal antibodies, only Daratumumab has been evaluated using this strategy.

This study seeks to evaluate the efficacy of mast cell stabilizer Montelukast (SINGULAIR) 10 mg in decreasing the SIR in patients receiving therapeutic MAs either alone or as part of chemoimmunotherapy in hematologic condition. The MAs being studied includes: Blinatumomab (BLINCYTO, Amgen Inc.), Daratumumab (DARZALEX, Janssen Biotech, Inc.), Elotuzumab (EMPLICIT, Bristol-Myers Squibb Company), Gemtuzumab (MYLOTARG, Pfizer Inc.), Obinutuzumab (GAZYVA, Genentech USA, Inc.), and Rituximab (RITUXAN, Genentech US); The investigators postulate that 10 mg of Montelukast, when given in addition to standard premedication, will lead to decrease in incidence of MA associated SIR, shorter infusion time and decrease use of additional health care resources

Detailed Description

Study design:

This is a Phase II single arm open label study evaluating 10 mg Montelukast given at least 2 hours prior to infusion of monoclonal antibody in addition to standard premedication. Monoclonal antibodies being evaluated include those commonly used to treat hematologic and oncologic malignancies like (Blinatumomab, Daratumumab, Elotuzumab, Gemtuzumab, Obinutuzumab, and Rituximab).

Arms/Intervention; Study subjects will be given 10 mg of Montelukast to be orally self-administered at least 2 hours prior to beginning of chemotherapy section Standard premedication will be administered according to institution protocol

Conditions

Infusion Reaction; Monoclonal Antibody

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Montelukast (Singulair)

Montelukast(Singulair) 10mg to be taken in addition to standard institutional premedication

Group Type: OTHER

Montelukast 10 Mg Oral Tablet

Intervention Type: DRUG

Montelukast(Singulair) 10mg to be taken at least 2 hours prior to initiation of monoclonal antibody infusion addition to institutional protocol premedication regiment

Interventions

Montelukast 10 Mg Oral Tablet

Montelukast(Singulair) 10mg to be taken at least 2 hours prior to initiation of monoclonal antibody infusion addition to institutional protocol premedication regiment

Intervention Type: DRUG

Other Intervention Names

Singulair

Eligibility Criteria

Inclusion Criteria

1. Patients must be at least 18 years.

2. Able to provide consent for study participation (English and Spanish).

3. Patients with hematologic disorders or malignancies starting on any of the following monoclonal antibodies alone or in combination with chemotherapy (Blinatumomab, Daratumumab, Elotuzumab, Gemtuzumab, Obinutuzumab, and Rituximab).

4. Able to tolerate leukotriene antagonist including Montelukast.

5. Able to tolerate oral intake.

6. Available for follow up by phone and on site.

Exclusion Criteria

1. Patients undergoing treatment with above monoclonal antibodies for indications other than stated in above eligibility criteria.

2. Patients who cannot provide informed consent in English or Spanish.

3. Patients taking Montelukast or other leukotriene antagonists for other indications at the time of screening.

4. Known allergic reactions to Montelukast or other leukotriene inhibitors.

5. On monoclonal antibodies other than the ones being studied (Blinatumomab, Daratumumab, Elotuzumab, Gemtuzumab, Obinutuzumab, and Rituximab).

6. History of uncontrolled depression or suicidal ideation or psychiatric illness.

7. Known Severe Hepatic Impairment (AST>10x ULN; ALT>10x ULN; ALP>10x ULN; and/or Bilirubin >5x ULN).

8. Patient with eosinophilic vasculitis.

9. Unable to comply with phone or in person follow-up.

10. Patients participating in another clinical trial.

11. Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Mohammed Bukari, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

MOHAMMED BUKARI, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF - Fresno

Locations

Community Cancer Institute

Clovis, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

IND146287

Identifier Type: OTHER

Identifier Source: secondary_id

IRB2019105

Identifier Type: -

Identifier Source: org_study_id