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

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

Tracking Information
First Submitted Date  ICMJE December 10, 2019
First Posted Date  ICMJE December 13, 2019
Last Update Posted Date November 2, 2022
Actual Study Start Date  ICMJE March 20, 2020
Estimated Primary Completion Date September 20, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Montelukast in Reducing the Incidence and Severity of Monoclonal Antibodies Associated Infusion Reactions
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Infusion Reaction
  • Monoclonal Antibody
Intervention  ICMJE 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  ICMJE Montelukast (Singulair)
Montelukast(Singulair) 10mg to be taken in addition to standard institutional premedication
Intervention: Drug: Montelukast 10 Mg Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2019)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 20, 2023
Estimated Primary Completion Date September 20, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard Ward 559.387.1828 ext 41828 rward@fresno.ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04198623
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE University of California, San Francisco
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: MOHAMMED BUKARI, MD UCSF - Fresno
PRS Account University of California, San Francisco
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP