A Study to Desensitize Allergic Reactions to Treatments for Blood Disorders

Desensitization of Immunomodulating Agent-Related Hypersensitivity Reactions as a Means to Provide Therapeutic Options in the Management of Plasma Cell Disorders (DeHyperPCD)

Patients with multiple myeloma (a type of blood cancer affecting the white blood cells) or amyloidosis (abnormal buildup of a protein called amyloid in the body) are often given treatment with the drugs lenalidomide or pomalidomide. Some patients may experience an allergic reaction to these drugs which would mean stopping the treatment.

The purpose of this research study is to see how safe and useful desensitization is in allowing patients to receive further treatment with lenalidomide or pomalidomide.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Amyloidosis
• Intervention / Treatment: Drug: Lenalidomide; Drug: Pomalidomide

Detailed Description

Some doctors believe that the body may be taught to react less or stop reacting to, the things that would otherwise trigger an allergic reaction. This is called desensitization. Desensitization is usually done with repeat exposure to the thing that causes the allergic reaction. For example, people who have allergies may receive small, controlled doses of the allergen over a period of time until the allergic reactions are tolerable or are stopped completely.

The researchers want to see if giving low doses of lenalidomide or pomalidomide to people who experienced an allergic reaction to these medications can become desensitized so that they are able to continue treatment for their disease with these drugs.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anca Prica, M.D.; Phone Number: 416-946-2249; Email: anca.prica@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed Informed Consent
• Adult patients 18 years old or older
• All study participants must be registered into the mandatory Lenalidomide or Pomalidomide Pregnancy Prevention Plan, and be willing and able to comply with the requirements.
• Females of reproductive potential must adhere to the pregnancy testing and contraceptive techniques as required by the Pregnancy Prevention Plan.
• Patient diagnosed with multiple myeloma or amyloidosis, with history of HSR to lenalidomide or pomalidomide, who had experienced moderate-severe (Grade ≥2 CTCAE v5.0) cutaneous reactions to IMiDs, with or without being symptomatic (itchy rash). Patients who developed HSR to IMiDs (lenalidomide or pomalidomide) will be assessed according to the CTCAE v 5.0 grading criteria during enrolment, and the severity of the grading (Grade ≥ 2 or otherwise) is recorded for the purpose of future subgroup analysis. OR
• Complained of angioedema or anaphylaxis reactions attributable to lenalidomide or pomalidomide.
• Patients must be afebrile at least 48 hours prior to proposed desensitization day.
• For patients with existing body rash, a complete resolution of rash is needed prior to Rapid Desensitization Program procedures at least 7 days prior to desensitization.
• Patients may continue to administer their current medication prior to the start of Rapid Desensitization Program (RDP). Best possible medication history will be taken prior to RDP, with the exception of withholding beta- blockers on the day of desensitization. Patient's allergy history will be documented.

Exclusion Criteria:

• Female who is pregnant or suspected of being pregnant or breast feeding or likely to breast feed during the study duration
• Inability to take oral medications.
• History of Steven-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
• Patients who are taking IMiDs-based therapy for an indication other than multiple myeloma (MM) and/or systemic amyloidosis (AL).
• The development of erythema nodosum, if characterized by a desquamating rash while taking thalidomide, IMiDs or similar drugs.
• Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or previous infection (HepB core Ab +, but HepB sAg negative) are eligible.
• Patients who, for whatever reason, are unable to tolerate IMiDs (other than hypersensitivity reactions).
• Patients who have completed 3 RDPs and continued to have breakthrough hypersensitivity reactions (HSR) post Rapid Desensitization Program (RDP).
• Patients who had experienced IMiDs-related hypersensitivity reaction that is less than Grade 2 (Grade 1) as per CTCAE v5.0.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; Participants will only receive lenalidomide if they had previously received this drug as a part of their treatment for multiple myeloma or amyloidosis and had experienced an allergic reaction to the drug. Participants will first be given a low dose of lenalidomide with increasing doses over 10-12 steps over 3.5 to 5 hours. Participants will be monitored for side effects or reactions prior to each dose step and any reactions will be managed before giving the increased dose at the next step. The final dose will be determined by the study doctor and is expected to be the dose that participants will restart treatment with lenalidomide at.	Drug: Lenalidomide; Lenalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).; Other Names: REVLIMID
Experimental: Pomalidomide; Participants will only receive pomalidomide if they had previously received this drug as a part of their treatment for multiple myeloma or amyloidosis and had experienced an allergic reaction to the drug. Participants will first be given a low dose of pomalidomide with increasing doses over 10-12 steps over 3.5 to 5 hours. Participants will be monitored for side effects or reactions prior to each dose step and any reactions will be managed before giving the increased dose at the next step. The final dose will be determined by the study doctor and is expected to be the dose that participants will restart treatment with pomalidomide at.	Drug: Pomalidomide; Pomalidomide is an antineoplastic and immunomodulatory agent that will be given as a liquid in syringes to be taken orally (by mouth).; Other Names: POMALYST

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants successfully completing desensitization program	12 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distress Assessment and Response Tool (DART) score	Rating of physical symptoms, practical concerns, and emotional concerns on a scale from 1-10. 0 = no symptoms/concerns, 10=worse possible experience of the symptom/concern	90 days post desensitization program
Edmonton Symptom Assessment System (ESAS) score	A rating of nine common symptoms on a scale from 0-10. 0 = no symptoms, 10=worse possible experience of the symptom	90 days post desensitization program
Frequency of interrupted treatment with immunomodulating agent		90 days post desensitization program
Duration of interrupted treatment with immunomodulating agent		90 days post desensitization program
Mortality rate associated with disease progression or treatment-related toxicity		90 days post desensitization program
Frequency of rash recurrence		90 days post desensitization
Duration of treatment with immunomodulating agent post desensitization		90 days post desensitization
Incidence of adverse events during desensitization procedures and hospital stay		12 days
Total duration of treatment with immunomodulating agent		90 days post desensitization
Duration of treatment with supportive care agents		90 days post desensitization

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Anca Prica, M.D., Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2020
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: May 8, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Multiple Myeloma; Amyloidosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Pomalidomide; Lenalidomide
• Other Study ID Numbers: DeHyperPCD; RV-CL-MM-PI-13170 (Other Identifier: Princess Margaret Cancer Centre)

Drug and device information, study documents

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