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

• ClinicalTrials.gov Identifier: NCT04198623
• Recruitment Status: Recruiting
• First Posted: December 13, 2019
• Last Update Posted: November 2, 2022
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): Mohammed Bukari, MD, University of California, San Francisco

Tracking Information

• First Submitted Date: December 10, 2019
• First Posted Date: December 13, 2019
• Last Update Posted Date: November 2, 2022
• Actual Study Start Date: March 20, 2020
• Estimated Primary Completion Date: September 20, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2019)

The incidence rates of standard infusion reaction(SIR) at cycle 1 and during subsequent cycles of monoclonal antibody infusion in the study subjects [ Time Frame: Through study completion (average 6 months) ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 11, 2019)

• Average infusion duration of each cycle the monoclonal antibody infusion in the study subject [ Time Frame: Through study completion (average 6 months) ]
  The time from start to end of each cycle of infusion of monoclonal antibody will be measured in the study subject up to 6 cycles or treatment discontinuation which ever comes first. Average infusion time will then be calculated.
• Incidence rate of Grade 3 or more monoclonal antibody infusion with each cycle of infusion and through out the entire duration of infusion (up to 6 cycles or till discontinuation which ever comes first [ Time Frame: Through study completion (average 6 months) ]
  The incidence rate of Grade 3 infusion reaction includes all clinical sign and symptoms of reaction graded by CTCAE v5.0 as grade 3 in patients receiving each cycle monoclonal antibody infusions and the entire duration of treatment(up to 6 cycles or till treatment is discontinue which ever comes first
• Discontinuation rate of monoclonal antibody infusion due to SIRs [ Time Frame: Through study completion (average 6 months) ]
  Rate at which monoclonal antibody treatment is stopped and changed to new treatment due to adverse drug reaction attributed to monoclonal antibody infusion

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Montelukast in Reducing the Incidence and Severity of Monoclonal Antibodies Associated Infusion Reactions
• Official Title: A Phase II Study, Evaluating the Efficacy of Montelukast in Reducing the Incidence and Severity of Monoclonal Antibodies Associated Infusion Reactions

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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care

Condition

• Infusion Reaction
• Monoclonal Antibody

Intervention

Drug: 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

Other Name: Singulair

Study Arms

Montelukast (Singulair)

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

Intervention: Drug: Montelukast 10 Mg Oral Tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 11, 2019): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 20, 2023
• Estimated Primary Completion Date: September 20, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Richard Ward; 559.387.1828 ext 41828; rward@fresno.ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04198623
• Other Study ID Numbers: IRB2019105; IND146287 ( Other Identifier: US FDA )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Incidence rate of Infusion reaction Tolerability of infusion reaction
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Sept, 2022

• Current Responsible Party: Mohammed Bukari, MD, University of California, San Francisco
• Original Responsible Party: University of California, San Francisco
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: MOHAMMED BUKARI, MD; UCSF - Fresno

• PRS Account: University of California, San Francisco
• Verification Date: October 2022