Prediction of Rituximab Hypersensitivity and Desensitization Treatment

This is a single-center prospective single arm study. The purpose of this study is to assess the usefulness of skin test as a diagnostic tool to predict the hypersensitivity to rituximab in Chinese population, evaluate the rate of hypersensitivity reactions (HSRs) after the application of active desensitization therapy in the case of a positive skin test result, and investigate the mechanism of HSRs to rituximab.

Study Overview

• Status: Unknown
• Conditions: Drug Hypersensitivity Reaction
• Intervention / Treatment: Diagnostic test: skin test

Detailed Description

Patients with B-cell lymphomas who need the administration of rituximab are recruited. They undergo skin tests with rituximab before the first infusion of this medicine. In the case of a positive skin test result, the patient will receive the desensitization procedure; if the result of skin test is negative, the challenge test will be administered. Drug challenge test consists in administering the desired full dose of rituximab according to manufacturer instructions. Challenge is considered positive when it shows an objective HSR. The patient with a positive challenge test will receive the desensitization procedure; while the patient with a negative challenge test will be given standard rituximab infusion in the subsequent chemotherapies.

Peripheral blood will be drawn from all the subjects during their initial infusion of rituximab. If the patient shows hypersensitive symptoms, the blood will be drawn one hour after the onset of reaction; while if the patient has no HSR in the whole infusion process, the blood will be drawn at the end of infusion and used as negative control. Levels of tryptase, specific immunoglobulin E to rituximab, IL-6, IL-8, and TNF-α in the serum will be tested.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Lisha Li; Phone Number: 8613661359318; Email: doctorlilisha@163.com
      • Contact: Yan Zhang; Phone Number: 8613810000485; Email: zhangyan10659@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with B cell lymphoma confirmed through pathological biopsy
• Patients who need the treatment of rituximab and have not received rituximab before

Exclusion Criteria:

• Pregnant or lactating women
• Patients taking antihistamines in three days before the skin tests
• Long-term use of systemic corticosteroid
• Patients with skin lesions including infection, dermatitis, trauma or scar in both arms
• Patients with acute attack of asthma
• Patients with psoriasis
• Other conditions that the researchers consider inappropriate to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Experimental group; Patients undergo diagnostic tests before the initial infusion of rituximab, including skin prick tests, intradermal tests, and challenge tests successively. If the skin test shows a positive result, the patient will receive desensitization procedure, and if the skin test is negative, the challenge test will be done, meaning normal infusion of rituximab according to manufacturer instructions. All the HSRs in the process of desensitization or normal infusion will be recorded. Peripheral blood will be drawn from all the subjects during their infusion to investigate the mechanism of HSRs to rituximab.

Diagnostic test: skin test; For skin prick tests (SPT), rituximab solution of 1mg/ml was applied on the volar aspect of the forearm. For intradermal tests (IDT), 0.02 mL of a 1:100 dilution (0.1mg/ml) of full-strength solution (10mg/ml) was injected first. If the result was negative, a 1:10 dilution（1mg/ml）was then used. As to the desensitization protocol, three solutions with different concentrations are delivered in 12 consecutive steps, each step increasing the rate of drug administration by 2- to 2.5-fold. Solution 1 is a 100-fold dilution (0.01mg/ml) of the final target concentration, solution 2 is a 10-fold dilution (0.1mg/ml) of the final target concentration, and the concentration of solution 3 is the target concentration (1mg/ml). Each step takes 15 minutes until the target rate of 200ml/h is reached, and the final step is prolonged to complete the target dose. The whole procedure takes about 5.5 hours.; Other Names: desensitization for patients with positive skin test results

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of skin test	The sensitivity and specificity of skin test in the prediction of HSR to rituximab.	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypersensitivity reactions (HSRs)	The rate of HSRs in all the enrolled subjects with the application of active desensitization therapy in the case of a positive skin test result.	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks
Tryptase	Level of serum tryptase	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks
Specific immunoglobulin E to rituximab	Level of serum specific immunoglobulin E to rituximab	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks
IL-6	Level of serum IL-6	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks
IL-8	Level of serum IL-8	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks
TNF-α	Level of serum TNF-α	From date of signing the informed consent until the end of induction chemotherapy, up to 32 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (ACTUAL): October 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Rituximab; Desensitization; Skin test; Drug hypersensitivity reaction
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Immune System Diseases; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity; Drug Hypersensitivity
• Other Study ID Numbers: PUMCH-Allergy-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No