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

NCT04198623 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB2019105IND146287
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Infusion Reaction; Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Standard Infusion Reactions (SIR) at Cycle 1 and During Subsequent Cycles of Monoclonal Antibody Infusion

  The incidence rate of infusion reaction includes all clinical sign and symptoms of reaction graded by CTCAE v5.0 in patients receiving each cycle monoclonal antibody infusions. The grade and rate of each grade will be measured and or calculated for each cycle of infusion up to 6 cycles or treatment discontinuation which ever comes first

  Through study completion (average 6 months)

Secondary Outcomes (3)

• Average Infusion Duration of Each Cycle of the Monoclonal Antibody Infusion in the Study Subject

  Through study completion (average 6 months)

• Incidence Rate of Grade 3 or More Monoclonal Antibody Infusion Throughout the Entire Duration of Infusion (up to 6 Cycles or Till Discontinuation Whichever Comes First)

  Through study completion (average 6 months)

• Discontinuation Rate of Monoclonal Antibody Infusion Due to SIRs

  Through study completion (average 6 months)

Other Outcomes (2)

• Infusion Data Cycle 1

  Cycle 1

• Infusion Data Cycle 2-6

  Cycle 2-6

Study Arms (1)

Montelukast (Singulair)

OTHER

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

Drug: Montelukast 10 Mg Oral Tablet

Interventions

Montelukast 10 Mg Oral Tablet DRUG

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

Also known as: Singulair

Montelukast (Singulair)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 18 years.
• Able to provide consent for study participation (English and Spanish).
• 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).
• Able to tolerate leukotriene antagonist including Montelukast.
• Able to tolerate oral intake.
• Available for follow up by phone and on site.

You may not qualify if:

• Patients undergoing treatment with above monoclonal antibodies for indications other than stated in above eligibility criteria.
• Patients who cannot provide informed consent in English or Spanish.
• Patients taking Montelukast or other leukotriene antagonists for other indications at the time of screening.
• Known allergic reactions to Montelukast or other leukotriene inhibitors.
• On monoclonal antibodies other than the ones being studied (Blinatumomab, Daratumumab, Elotuzumab, Gemtuzumab, Obinutuzumab, and Rituximab).
• History of uncontrolled depression or suicidal ideation or psychiatric illness.
• Known Severe Hepatic Impairment (AST\>10x ULN; ALT\>10x ULN; ALP\>10x ULN; and/or Bilirubin \>5x ULN).
• Patient with eosinophilic vasculitis.
• Unable to comply with phone or in person follow-up.
• Patients participating in another clinical trial.
• Pregnancy

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Community Cancer Institute

Clovis, California, 93611, United States

Location

MeSH Terms

Interventions

montelukast; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Mohammed Sani Bukari MD, Associate clinical professor
• Organization: UCSF Fresno/Community Cancer Institute

Mohammed.Bukari@ucsf.edu

3473019055

Study Officials

• MOHAMMED BUKARI, MD

  UCSF - Fresno

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 13, 2019
• Study Start: March 20, 2020
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: December 15, 2025
• Results First Posted: December 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Sept, 2022

Locations

US (1)